ARTICLE | doi:10.20944/preprints202007.0317.v1
Subject: Life Sciences, Other Keywords: pear trees; TIMAC AGRO Italia; growth regulator; sustainable development; plant nutrition
Online: 15 July 2020 (05:57:57 CEST)
Agricultural Production today has to deal with different challenges. It has to increment production for a continuously increasing population, reducing the environmental burdens on the natural systems. In conventional agriculture, this is possible through the increase of inputs, especially nutrients, which, however, are responsible for the biggest part of emissions. It becomes more complicated though, adopting sustainable agricultural practices, to improve the quality and the quantity of agricultural production reducing the inputs use. Plant growth regulators are described in the literature for the significant role in securing crop management of modern agriculture. Therefore, this joint field experiment has been carried out on a pear orchard (Pyrus communis L. cv. Abate Fètel) in Emilia Romagna (Italy) by Fondazione Navarra and TIMAC AGRO Italia S.p.A., to test the “less for more” theory which consists in getting more and better agricultural produce using fewer inputs. Preliminary results of two consecutive years have confirmed our assumption as it was possible to substantially reduce the total fertilisation units applied, improving significantly quantitative and qualitative production indicators (i.e. flower and fruit density, fruit set (%), the average weight of fruits (g) and the total yield (t/ha)). Results have also shown a positive correlation between plant growth regulators and agronomic efficiency of pears.
Sun, 12 July 2020
HYPOTHESIS | doi:10.20944/preprints202003.0419.v4
Subject: Life Sciences, Other Keywords: the origin of the genetic code; the ATP hypothesis; the first key building block in the probiotic soup; coevolution of the genetic code with biochemical system; from energy transformation to informatization and structuralization; cyclizing of polynucleotides and polypeptides
Online: 12 July 2020 (14:28:35 CEST)
More than half a century has passed since the discovery of the genetic code, but its origin is still one of the greatest mysteries in life science, although a plenty of theories have been proposed so far, as none can explain satisfactorily why the genetic code evolved in such a way, especially in the context of the biochemical system, a relation of part to whole. Here, a new hypothesis is proposed, according to which ATP is at the origin of the genetic code by its coevolution with the pristine biochemical system of the protocell. This hypothesis shows how primitive life with its genetic code emerged through a series of processes from energy flow to information communication mediated by ATP. First, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the extant biochemical systems. Second, ATP serves as not only an energy carrier but also an informatization molecule, as ATP could energetically elongate chains of both polynucleotides and polypeptides, thus providing a bridge between these molecules and eventually mediating biochemical innovation in the protocell from energy transformation to informatization, a process for creating and managing information. Informatization was inevitably coupled with structuralization (processes for organizing or incorporating cellular structures), cyclizing polynucleotides and polypeptides into a feedback loop of reciprocal causation. The triplet codon might be only for stereochemical handling of amino acids through, e.g., Watson–Crick pairing interactions. It is only the evolutionary completion of the genetic code from RNA to DNA that, contrary to the central dogma, marked the dawn of cellular life, when Darwinian evolution began to operate. The ATP hypothesis sheds light on the origin of life, together with the formation of both photosynthetic and biochemical systems, which remains largely unknown thus far.
Sat, 11 July 2020
Subject: Life Sciences, Other Keywords: MIF; Lingulodinium polyedra; transmembrane protein; dinoflagellate; stress response; secretion
Online: 11 July 2020 (17:23:36 CEST)
Macrophage Migration Inhibitory Factors (MIF) are pivotal cytokines/chemokines for vertebrate immune systems. MIFs are typically soluble single-domain proteins that are conserved across plant, fungal, protist, and metazoan kingdoms but their functions have not been determined in most phylogenetic groups. Here we describe an atypical multidomain MIF protein. The marine dinoflagellate Lingulodinium polyedra produces a transmembrane protein with an extra-cytoplasmic MIF domain, which localizes to cell wall-associated membranes and vesicular bodies. This protein is also present in the membranes of extracellular vesicles accumulating at the secretory pores of the cells. Upon exposure to biotic stress, L. polyedra exhibits reduced expression of the MIF gene and reduced abundance of the surface-associated protein. These findings indicate that the transmembrane MIF may contribute to intercellular communication and/or interactions between free-living organisms in multispecies planktonic communities and raise the question of possible analogies in MIF functions between cells of metazoan organisms and protist communities.
Tue, 7 July 2020
REVIEW | doi:10.20944/preprints202007.0123.v1
Subject: Life Sciences, Other Keywords: causal interactions; databases; interoperability; biological pathway; logical modeling; computational biology
Online: 7 July 2020 (09:50:40 CEST)
Causal molecular interactions represent key building blocks used in computational modeling, where they facilitate the assembly of regulatory networks. These regulatory networks can then be used to predict biological and cellular behavior by system perturbations and in silico simulations. Today, broad sets of these interactions are being made available in a variety of biological knowledge resources. Moreover, different visions, based on distinct biological interests, have led to the development of multiple ways to describe and annotate causal molecular interactions. Therefore, data users can find it challenging to efficiently explore resources of causal interaction and to be aware of recorded contextual information that ensures valid use of the data. This manuscript presents a review of public resources collecting causal interactions and the different views they convey, together with a thorough description of the export formats established to store and retrieve these interactions. Our goal is to raise awareness amongst the targeted audience, i.e., logical modelers, but also any scientist interested in molecular causal interactions, about existing data resources and how to get familiar with them.
REVIEW | doi:10.20944/preprints202007.0119.v1
Subject: Life Sciences, Other Keywords: Donkey milk; donkey colostrum; mammal’s milk; bioactive peptides; biologic activity; health benefits
Online: 7 July 2020 (08:57:01 CEST)
Due to its similarity with human milk and its low allergenic properties, donkey milk has long been used as an alternative for infants and patients with cow's milk protein allergy. In addition, this milk is attracting growing interest in human nutrition because of presumed health benefits. It has antioxidant, antimicrobial, antitumoral, antiproliferative, and antidiabetic activity. Also, it stimulates the immune system, regulates the gastrointestinal flora, and prevents inflammatory diseases. Although all components of donkey milk can contribute to functional and nutritional effects, it is generally accepted that the whey protein fraction plays a major role. The purpose of this review is to highlight the active proteins and peptides of donkey milk in comparison with other types of milk, emphasizing their properties and their roles in different fields.
Mon, 6 July 2020
REVIEW | doi:10.20944/preprints202007.0095.v1
Subject: Life Sciences, Other Keywords: COVID-19; agriculture; food industry; applied research; technology transfer; sustainability; Italy
Online: 6 July 2020 (04:13:40 CEST)
The recent outbreak of a new Coronavirus has developed into a global pandemic with about 10,5 million reported cases and over 500,000 deaths worldwide. Our prospective paper reports an updated analysis of the impact that this pandemic had on the Italian agri-food sector during the national lockdown and discusses why and how this unprecedented economic crisis could be a turning point to deal with the overall sustainability of food and agricultural systems in the frame of the forthcoming European Green Deal. Its introductory part includes a wide-ranging examination of the first quarter of pandemic emergency, with a specific focus on the primary production, to be understood as agriculture (i.e. crops and livestock, and their food products), fisheries and forestry. The effect on the typical food and wine exports, and the local environment tourism segments is also taken into account in this analysis, because of their old and deep roots into the cultural and historical heritage of the country. The subsequent part of the paper is centered on strategic lines and research networks for an efficient socio-economic and territorial restart, and a faster transition to sustainability in the frame of a circular bio-economy. Particular emphasis is given to the urgent need of investments in research and development concerning agriculture, in terms of not only a fruitful penetration of the agro-tech for a next-generation agri-food era, but also a deeper attention to the natural and environmental resources, including forestry. As for the rest of Europe, Italy demands actions to expand knowledge and strengthen research applied to technology transfer for innovation activities aimed at providing solutions for a climate neutral and resilient society, in reference to primary production to ensure food security and nutrition quality. Our expectation is that science and culture return to play a central role in national society, as their main actors are capable of making a pivotal contribution to renew and restart the whole primary sector and agri-food industry, addressing also social and environmental issues, and so accelerating the transition to sustainability.
Sun, 5 July 2020
REVIEW | doi:10.20944/preprints202007.0068.v1
Subject: Life Sciences, Other Keywords: Microbiome; Plant Immunity; Priming; Transgenerational Immune Priming (TGIP)
Online: 5 July 2020 (11:35:04 CEST)
One of the biggest demanding situations for food security in the 21st century is to enhance crop yield stability through the improvement of diseases-resistant crops. Managing plant health is a major challenge for modern food production and compounded by the lack of common ground among the many disease control disciplines involved. All plants simultaneously engage with billions of microbes which can be collectively referred to as the plant microbiome. Most microbes inside the plant microbiome are harmless or even beneficial to the plant as they promote plant growth or provide protection in opposition to diseases. However, some of these microbes also cause disease with devastating effects on crop yields. To prevent pathogen infection, plants have evolved an advanced innate immune system that recognizes conserved cell surface molecules that most pathogen possesses. Activation of the plant immune system stops the invading pathogen, however this comes with fitness cost that significantly reduces plant growth and leads to yield penalty. Apart from their innate immune system controlling pre-programmed defense reactions, plants can also increase the responsiveness of their immune system in response to selected environmental signals. This phenomenon is known as “defense priming”. Although defense priming rarely provides full protection, its broad-spectrum effectiveness, low-fitness cost, long‐lasting durability and inherited to future generations make it attractive for sustainable crop protection.
REVIEW | doi:10.20944/preprints202007.0053.v1
Subject: Life Sciences, Other Keywords: thalamocortical loop; thalamus; microcircuit; modeling; reticular nucleus; somatosensory system; ventral posteromedial nucleus; ventral posterolateral nucleus; posterior nucleus; thalamic relay cells; thalamic interneurons; rodent
Online: 5 July 2020 (07:45:16 CEST)
As our understanding of the thalamocortical system deepens, the questions we face become more complex. Their investigation requires the adoption of novel experimental approaches complemented with increasingly sophisticated computational modeling. In this review, we take stock of current data and knowledge about the circuitry of the somatosensory thalamocortical loop in rodents, discussing common principles across modalities and species whenever appropriate. We review the different levels of organization, including the cells, synapses, neuroanatomy, and network connectivity. We provide a complete overview of this system that should be accessible for newcomers to this field while nevertheless being comprehensive enough to serve as a reference for seasoned neuroscientists and computational modelers studying the thalamocortical system. We further highlight key gaps in data and knowledge that constitute pressing targets for future experimental work. Filling these gaps would provide invaluable information for systematically unveiling how this system supports behavioral and cognitive processes.
Fri, 3 July 2020
REVIEW | doi:10.20944/preprints202007.0020.v1
Subject: Life Sciences, Other Keywords: High homogenization pressure; food functionality; bioactive components; agri-food waste; sustainability
Online: 3 July 2020 (08:39:05 CEST)
The interest in high homogenization pressure technology has grown over the years. It is a green technology with low energy consumption, not generating high CO2 emissions or polluting effluents. The main food applications derive from its effect on particle size, causing a more homogeneous distribution of fluid elements (particles, globules, droplets, aggregates, etc.) and favouring the release of intracellular components; and its effect on the structure and configuration of chemical components such as polyphenols and macromolecules such as carbohydrates (fibres) and proteins (also microorganisms and enzymes). The challenges of the 21st century lead food industry processing towards obtaining food with high nutritional quality and taking advantage of waste to obtain ingredients with specific properties. For this purpose, soft and non-thermal technologies such as high pressures homogenization have a huge potential. The objective of this work is to review how the need to combine safety, functionality and sustainability in food industry has conditioned the last decade applications of high-pressure homogenization technology.
Sun, 28 June 2020
ARTICLE | doi:10.20944/preprints202006.0346.v1
Subject: Life Sciences, Other Keywords: COVID-19, assessment; global; social and economic factors; correlation and regression analysis
Online: 28 June 2020 (19:55:55 CEST)
The COVID-19 outbreak has severely affected the social and economic conditions across this globe. Little is known about the relationship of COVID-19 with countries’ economic and socio-demographic status. Publicly available data on COVID-19 test rate, attack rate, case fatality rate, and recovery rate were analyzed in relation to country’s economic status, population density, median age, and urban population ratio. We also conducted multinomial logistic regression analysis to predict the influence of countries’ social and economic factors on COVID-19. The results revealed that the median age had significant positive correlation with attack rate (r=0.2389, p=0.003), case fatality rate (r=0.3207, p=0.000) and recovery rate (r=0.4847, p=0.000). The urbanization has positive significant correlation with recovery rate (r=0.1957, p= 0.016). The multinomial logistic regression analysis revealed low-income countries are less likely to have an increased recovery rate (p=0.000) and attack rate (p=0.016) compare to high-income countries. The lower-middle-income and upper-middle-income countries are less likely to have an increased recovery rate (p=0.000 and p=0.001, respectively) compared to high-income countries. Based on the result of this study, these economic and socio-demographic factors should consider in designing appropriate preventive measures as a next step. The low and lower-middle-income countries should invest more in health care services to lower the case fatality rate and increase test and recovery rates as part of pandemic preparation like COVID-19. As the number of COVID-19 attacks, death and recovery rates are constantly changing; however, the intensive study is required to obtain a clear picture.
Fri, 26 June 2020
REVIEW | doi:10.20944/preprints202006.0319.v1
Subject: Life Sciences, Other Keywords: glia; central nervous system; COVID-19; SARS; MERS; coronavirus
Online: 26 June 2020 (17:32:55 CEST)
With confirmed COVID-19 cases surpassing the 8.5 million mark around the globe, there is an imperative need to deepen the efforts from the international scientific community to gain comprehensive understanding of SARS-CoV-2. Although the main clinical manifestations are associated with respiratory or intestinal symptoms, reports of specific and non-specific neurological signs and symptoms, both at presentation or during the course of the acute phase, are increasing. Approximately 25-40% of the patients present neurological symptoms. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the Central Nervous System (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood-brain barrier (BBB). Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for MERS-CoV. Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to dysbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this work we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV, explore the potential role for astrocytes and microglia in the infection and neuroinflammation, and compare them with the previously described human and animal CoV that showed neurotropism. We also propose possible underlying mechanisms by focusing on our knowledge of glia, neurons, and their dynamic intricate communication with the immune system.
Tue, 16 June 2020
REVIEW | doi:10.20944/preprints202006.0200.v1
Subject: Life Sciences, Other Keywords: exosomes; micro vesicles; extracellular vesicles; mesenchymal stromal cells (MSC); miRNA; cell therapy; artificial nano particles
Online: 16 June 2020 (07:57:00 CEST)
Extracellular vesicles (EV) such as exosomes, are newly recognized fundamental, natural and physiologic particles of life that seemingly are involved all biologic processes and clinical diseases. Due to their universal involvements, understanding the nature and the potential therapeutic uses of these nano-vesicles requires innovative experimental approaches, in virtually every field. Of the EV group, exosome nano-vesicles and larger companion extracellular micro vesicles (MV) can mediate completely new phenomena dependent on intercellular transfer of proteins and selected RNAs; particularly miRNAs, between donor and targeted cells to elicit epigenetic alterations inducing functional cellular changes. These recipient acceptor cells are nearby (paracrine transfers) or far away after distribution via the circulation (endocrine transfers). The major properties of such vesicles seem to have been conserved over eons, suggesting that they may have ancient evolutionary origins arising perhaps even before cells in the primordial soup from which life evolved. Their potential ancient evolutionary attributes may be responsible for the ability of some modern day exosomes to withstand unusually harsh conditions; perhaps due to unusual membrane lipid compositions. This is exemplified by maternal milk exosome survival of the neonatal acid/enzyme rich stomach. It is postulated that this also applies to their durable presence in phagolysosomes; suggesting unique intracellular release of contents. A major issue discussed is the generally poorly realized superiority of these naturally evolved nano vesicles to therapies compared human engineered artificial nanoparticles; say for treatment of cancers.
Fri, 12 June 2020
ARTICLE | doi:10.20944/preprints202006.0144.v1
Subject: Life Sciences, Other Keywords: Corynebacterium pseudotuberculosis; RNA-Seq; co-expression networks; influence genes; stress condition; causal genes
Online: 12 June 2020 (08:46:02 CEST)
Corynebacterium pseudotuberculosis is a Gram-positive bacterium that causes caseous lymphadenitis, a disease that predominantly affects sheep, goat, cattle, buffalo, and horses, but has also been recognized in other animals. This bacterium generates a severe economic impact on countries producing meat. Gene expression studies using RNA-seq is one of the most commonly used techniques to perform transcriptional experiments. Computational analysis on such data through reverse-engineering algorithms leads to a better understanding of the genome-wide complexity of gene interactomes, enabling the identification of genes having the most significant functions inferred by the activated stress response pathways. In this study, we identified the influential or causal genes from four RNA-seq data-sets from different stress conditions (high iron, low iron, acid, osmosis, and PH) in C. pseudotuberculosis, using a consensus-based network inference algorithm called miRsig and identified the causal genes in the network using the miRinfluence tool, which is based on the influence diffusion model. We found that over 50\% of the genes identified as influential have some essential cellular functions in the genomes. In the strains analyzed, most of the causal genes have crucial roles or participate in processes associated with response to extracellular stresses, pathogenicity, membrane components, and essential genes. This research brings new insight into the understanding of virulence and infection by C. pseudotuberculosis.
Thu, 11 June 2020
ARTICLE | doi:10.20944/preprints202006.0134.v1
Subject: Life Sciences, Other Keywords: time-restricted feeding; cafeteria diet; obesity; lipid profiles; atherogenic indices; browning adipose tissue
Online: 11 June 2020 (11:56:11 CEST)
Time-restricted feeding (TRF) showed a potent effect in preventing obesity and improving metabolic outcomes in several animal model of obesity; however, there is, as yet, scarce evidence about its effectiveness against obesogenic challenge that more accurately mimic the human Western diets, such as cafeteria diet. Moreover, the mechanism for its efficacy is poorly understood. White adipose browning has been linked to body weight loss. Herein, we tested whether TRF has the potential to induce browning of inguinal white adipose tissue (iWAT) and to attenuate obesity and associated dyslipidemia in cafeteria diet-induced obesity model. Male Wistar rats, fed normal laboratory chow (NC) or cafeteria diet (CAF) for 16 weeks, were subdivided into two groups that were subjected to either ad libitum (ad lib, A) or TRF (R) for 8 hours per day. Rats under TRF regimen had a lower body weight gain and adiposity compared with their diet-matched ad lib rats, despite equivalent levels of food intake and locomotor activity. In addition, TRF improved the deranged lipid profile [total cholesterol (TC); triglycerides (TG); high density lipoprotein (HDL-c); low density lipoprotein (LDL-c)] and atherogenic indices [atherogenic index of plasma (AIP); atherogenic coefficient (AC); coronary risk index (CRI)] in rats fed CAF diet. Remarkably, TRF resulted in decreased size of adipocytes and induced emergence of multilocular brown-like adipocytes in iWAT of NC- and CAF-fed rats. Protein expression of browning markers, such as uncoupling protein-1 (UCP1) and peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC1α) in iWAT were also up-regulated in time restricted NC- or CAF-fed rats. These findings suggest that TRF regimen is an effective strategy to improve obesity and associated dyslipidemia induced by CAF-diet, probably via a mechanism involving WAT browning process.
Sun, 7 June 2020
Subject: Life Sciences, Other Keywords: Kinase Inhibitor; NEK2; Chemoresistance; Avicennia marina; Marine compounds; Molecular docking; Cancer
Online: 7 June 2020 (11:16:35 CEST)
Never in mitosis gene A-related kinase 2 (NEK2) a member of serine-threonine kinase protein mainly involved in the cell cycle process. Clinical studies revealed NEK2 overexpression in various tumour types, also NEK2 was reported for their association with genetic abnormalities like mitotic machinery deregulation and chromosomal instability. Besides NEK2 plays a key role in maintaining the transformed phenotype of cancer cells and chemo-resistance of several tumour types. Thus, NEK2 transcriptional profile is important for diagnosis, treatment, and prognosis stages of cancer studies. Screening of novel NEK2 inhibitor would be beneficial in developing the specific lead molecules. Our studies involved NEK2 transcriptional profile search, screening of druggable cavities in NEK2, Drug likeliness of mangrove derived naphthoquinone derivatives avicennoneA , avicennoneB , avicennoneC , avicennoneD , avicenoneE , avicennone F , and avicennone G , avicequinone A, stenocarpoquinone B , avicequinone C , avicenol A , avicenol C,brugine, apigenin, chrysin and molecular docking studies to assess MNC compounds binding efficacy towards NEK2. Mangrove derived compounds conferred the intermolecular hydrogen bond, Pi-alkyl,pi-cation interactions with NEK2 kinase domain region residues Tyr 19, Lys 37, Arg 164, Lys174. Nearly 200 kinase proteins contained this promising Cys 22 residue as its positioned in the catalytic site like NEK family proteins. Avicenna A, Avicennone G, Chrysin and Brugine formed the irreversible covalent binding with NEK2 through Cys 22, thus they can be considered as potential kinase inhibitors with the limited off-target response. But these MNC compounds need to be tested further in invitro and invivo studies to propose as potent NEK2 inhibitors.
REVIEW | doi:10.20944/preprints202006.0078.v1
Subject: Life Sciences, Other Keywords: COVID-19; vaccine; vaccine development; vaccine discovery; systems biology; machine learning; platform technologies; adjuvants; smart clinical trials; human genetics; regulatory convergence; real world evidence; vaccines safety
Online: 7 June 2020 (10:11:02 CEST)
The urgency to develop vaccines against Covid-19 is putting pressure on the long and expensive development timelines which are normally required for development of lifesaving vaccines. There is a unique opportunity to take advantage of new technologies, smart and flexible design of clinical trials, and evolving regulatory science to speed up vaccine development against Covid-19 and transform vaccine development altogether.
REVIEW | doi:10.20944/preprints202006.0061.v1
Subject: Life Sciences, Other Keywords: diabetes; saffron; turmeric; food supplements; supplementation; physical exercise
Online: 7 June 2020 (06:01:12 CEST)
Diabetes Mellitus is one of the most prevalent chronic diseases in the world and one of its main features is chronic hyperglycemia. Among the therapeutic forms used to control the pathology are pharmacotherapy and the use of other alternatives such as regular exercise, which participates in glycemic control and the ingestion of plant extracts with antioxidant effects in the body. Among the different plants used, curcumin is a possible plant to be used to attenuate the hyperglycemic picture triggered by Diabetes Mellitus. Some studies suggest that this plant is antioxidant and hypoglycemic. The review aimed to know the antioxidant and hypoglycemic potential of curcumin supplementation in DM. The search was performed considering articles published between 2010 to 2019, in English and Portuguese, and a theoretical survey of relevant information was conducted in the main databases of scientific publications: Virtual Health Library and its indexed databases as Pubmed, LILACS, Scielo and Scientific Electronic Library Online. The associated use Turmeric and Physical Exercise demonstrated antioxidant, anti-inflammatory and hypoglycemic activity caused by Diabetes Mellitus. We may suggest that these are potential therapeutic ways to improve the quality and survival of diabetic patients.
Sun, 31 May 2020
Online: 31 May 2020 (18:28:15 CEST)
Dengue is one of the life-threatening common neglected tropical diseases of the world, yet to develop any therapeutic for its treatment and prevention. Although there is a licensed vaccine reported, but becomes less efficacious due to the presence of multiple serovars of the dengue virus (DENV). Thus, an efficacious dengue vaccine potent to work against all the serovars is very crucial and time-demanding. Here we used a comprehensive hierarchical reverse vaccinology approach to design an epitope-based vaccine, targeted against multiple serovars of the DENV. Conservancy and population coverage analysis of the promiscuous epitopes revealed the robust immune response against multiple serovars of the DENV and various ethnicities. Final vaccine constructs comprising of B and T-cell epitopes, Universal pan-HLA DR or PADRE (AKFVAAWTLKAAA) sequence, and an adjuvant (β-defensin) at N-terminal of the construct with suitable linkers. Physiochemical properties and secondary structure profiling of the vaccine protein secured its hydrophilic, thermostable, and other structural nature. Molecular docking analysis indicates the deep binding of the proposed vaccine in the binding groove of the human immune TLR4 receptor present on the dendritic cell. In addition, disulfide engineering was coped to extend its stability. Furthermore, molecular dynamics simulation of the modeled vaccine-TLR8 complex showed minimum deformability. Finally, in silico cloning approach of the vaccine construct within an expression vector (pET28a+) assure good expression. Proposed vaccine may give novel insights for treatment of dengue patients.
Thu, 28 May 2020
REVIEW | doi:10.20944/preprints202005.0460.v1
Subject: Life Sciences, Other Keywords: extracellular vesicles; exosomes; neural tissue repair; neuroregeneration; non-human primates; hydrogels; neural tissue engineering; stroke; cortical injury
Online: 28 May 2020 (13:08:32 CEST)
Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.
Wed, 27 May 2020
ARTICLE | doi:10.20944/preprints202005.0450.v1
Subject: Life Sciences, Other Keywords: epidemiology; transmission dynamics; isolated population; Spain
Online: 27 May 2020 (09:05:14 CEST)
Background: Since March 2020, Spain is severely hit by the ongoing pandemic of coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding and disrupting the early transmission dynamics of the infection is crucial for impeding sustained transmission. Methods: We recorded all COVID-19 cases and traced their contacts in an isolated rural community. We also sampled 10 households, 6 public service sites and the wastewater from the village sewage for environmental SARS-CoV-2 RNA. Results: The first village patient diagnosed with COVID-19-compatible symptoms occurred on March 3, 2020, twelve days before lockdown. A peak of 39 cases occurred on March 30. By May 15, the accumulated number of symptomatic cases was 53 (6% of the population), of which only 22 (41%) had been tested and confirmed by RT-PCR as SARS-CoV-2 infected, including 16 hospitalized patients. Contacts (n=144) were six times more likely to develop symptoms. Environmental sampling detected SARS-CoV-2 RNA in two households with known active cases and in two public service sites: the petrol station and the pharmacy. Samples from other sites and the wastewater tested negative. Conclusions: The low proportion of patients tested by RT-PCR calls for urgent changes in disease management. We propose that early testing of all cases and their close contacts would reduce infection spread, reducing the disease burden and fatalities. In a context of restricted testing, environmental RNA surveillance might prove useful for early warning and to identify high-risk settings enabling a targeted resource deployment.
ARTICLE | doi:10.20944/preprints202005.0374.v2
Subject: Life Sciences, Other Keywords: natural cosmetics; organic cosmetics; green cosmetics; cosmetology; certification
Online: 27 May 2020 (05:02:20 CEST)
The market of natural and organic cosmetics has been growing in last decades. The increase in interest in this type of product is a consequence of the concern that consumers have been presenting in relation to the environment and health. In addition to the appreciation the use of sustainable ingredients in cosmetic formulations, the consumers are also concerned about pollution caused by the use of plastics, which leads industries to reinvent themselves and rethink about the composition of packaging. The factor that most drives the purchase of natural and organic cosmetics is the fact that the consumer, in addition to contributing to the preservation of the environment, is also using a sustainable product. The growing demand for natural and organic cosmetics results in a concern of the brands with the organic issue, with the decreased use of animal derived ingredients and with the updating the parameters required for certification of a cosmetic as natural or organic. Due to the few studies available in this area, the importance of clarifying the definitions and concepts of natural and organic cosmetics is evident, in order to contribute with accurate information for the cosmetic sector.
Sun, 24 May 2020
COMMUNICATION | doi:10.20944/preprints202005.0401.v1
Subject: Life Sciences, Other Keywords: SARS-CoV-2; Peptide Vaccine; Spike Protein; Vaccinomics; Epitope Prediction
Online: 24 May 2020 (19:11:19 CEST)
SARS-CoV-2 has been the talk of the town ever since the beginning of 2020. The pandemic has brought the complete world on a halt. Every country is trying all possible steps to combat the disease ranging from shutting the complete economy of the country to repurposing of drugs and vaccine development. The rapid data analysis and widespread tools, software and databases have made bioinformatics capable of giving new insights to the researchers to deal with the current scenario more efficiently. Vaccinomics, the new emerging field of bioinformatics uses concepts of immunogenetics and immunogenomics with in silico tools to give promising results for wet lab experiments. This approach is highly validated for the designing and development of potent vaccines. The present in-silico study was attempted to identify peptide fragments from spike surface glycoprotein that can be efficiently used for the designing and development of epitope-based vaccine designing approach. Both B-cell and T-cell epitopes are predicted using integrated computational tools. VaxiJen server was used for prediction of protective antigenicity of the protein. NetCTL was studied for analyzing most potent T cell epitopes and its subsequent MHC-I interaction through tools provided by IEDB. 3D structure prediction of peptides and MHC-I alleles (HLA-C*03:03) was further done to carry out docking studies using AutoDock4.0. Various tools from IEDB were used to predict B-cell epitopes on the basis of different essential parameters like surface accessibility, beta turns and many more. Based on results interpretation, the peptide sequence from 1138-1145 amino acid and sequence WTAGAAAYY and YDPLQPEL were obtained as a potential B-cell epitope and T-cell epitope respectively. This in-silico study will help us to identify novel epitope-based peptide vaccine target in spike protein of SARS-CoV-2. Further, in-vitro and in-vivo study needed to validate the findings.
Sat, 23 May 2020
ARTICLE | doi:10.20944/preprints202005.0374.v1
Subject: Life Sciences, Other Keywords: natural cosmetics; organic cosmetics; green cosmetics; cosmetology; certification
Online: 23 May 2020 (10:52:01 CEST)
The market of natural and organic cosmetics has been growing in last decades. The increase in interest in this type of product is a consequence of the concern that consumers have been presenting in relation to the environment and health. In addition to the appreciation the use of sustainable ingredients in cosmetic formulations, the consumers are also concerned about pollution caused by the use of plastics, which leads industries to reinvent themselves and rethink about the composition of packaging. The factor that most drives the purchase of natural and organic cosmetics is the fact that the consumer, in addition to contributing to the preservation of the environment, is also using a sustainable product. The growing demand for natural and organic cosmetics results in a concern of the brands with the organic issue, with the decreased use of animal derived ingredients and with the updating the parameters required for certification of a cosmetic as natural or organic.
Fri, 22 May 2020
REVIEW | doi:10.20944/preprints202002.0465.v2
Subject: Life Sciences, Other Keywords: vitamin D; calcium; bone mass; osteoporosis; dairy foods; fortified foods
Online: 22 May 2020 (05:18:43 CEST)
Background: Vitamin D and calcium are important dietary compounds that affect bone mass, even if other minerals (potassium, zinc, etc.) and other vitamins (A, C and K) are also involved. Vitamin D and other minerals, in fact, play an important role in calcium homeostasis and calcium absorption. Hip fractures incidence is higher in western countries, where calcium is frequently included in human diet, while the occurrence of these fractures is lower in developing countries, where diets are often poor in calcium. This situation is known as the “calcium paradox”, and may be partially explained considering phosphate toxicity, that can induce a disorder of mineral metabolism. It is important to maintain adequate dietary calcium-phosphate balance in order to perform a healthy life, reducing the risk of osteoporotic fracture in older people. Vitamin D can also act as a hormone; vitamin D2 (ergocalciferol) is derived from the UV-B radiation of ergosterol, the vitamin D precursor naturally found in plants, fungi, and invertebrates. Vitamin D3 (cholecalciferol) is originated by sunlight exposure from 7-dehydrocholesterol, a precursor of cholesterol that can also act as a provitamin D3. Dietary intake of vitamin D3 is very important when skin is exposed for short times to ultraviolet B light (UV-B) one of the three kinds of invisible light rays together with UV-A and UV-C. This can be considered the usual situation in northern latitudes and in winter season, or the typical condition for older people and/or for people with very white delicate skin. Actually, the recommended daily intake of dietary vitamin D is strictly correlated with age, ranging from 5 μg for infants, children, teen-agers and adults, including women during pregnancy and lactation, to 15 μg for people over 65 years.
Thu, 21 May 2020
ARTICLE | doi:10.20944/preprints202005.0343.v1
Subject: Life Sciences, Other Keywords: GALAXY; Assembly; Annotation; Genomic Variants Discovery; Workflow
Online: 21 May 2020 (09:57:42 CEST)
Citizen Science has come up to perform analytics over the SARS-CoV-2 genome. Public GALAXY servers provide an automated platform for genomics analysis. Study includes design of GALAXY workflows for RNASEQ assembly and annotation as well as genomic variant discovery and perform analysis across four samples of SARS-CoV-2 infected humans obtained from the local population of Wuhan, China. It provides information about transcriptomics and genomic variants across the SARS-CoV-2 genome. Study can be extended to perform evolutionary and comparative study across each species of coronaviruses. Augmented and integrated study with cheminformatics and immunoinformatics will be a way forward for drug discovery and vaccine development.
Wed, 20 May 2020
REVIEW | doi:10.20944/preprints202005.0329.v1
Subject: Life Sciences, Other Keywords: sustainable agriculture; carbon sequestration; crop productivity; soil acidification; soil organic matter; pyrolysis; microbial activity, biochar
Online: 20 May 2020 (11:04:28 CEST)
The sustainable production of food faces formidable challenges. Foremost is the availability of arable soils, which have been ravaged by the overuse of fertilizers and detrimental soil management techniques. As such, maintenance of soil quality, and reclamation of marginal soils, has become an increasingly important endeavor. Recently, there has been emerging interest in the use of biochar, a carbon rich, porous material thought to improve various aspects of soil performance. Biochar (BC) is produced through the thermochemical decomposition of organic matter at high temperature in an oxygen limited environment, in a process known as pyrolysis. Importantly, the source of organic material, or ‘feedstock,’ used in this process and different parameters of pyrolysis, especially temperature, determine the chemical and physical properties of biochar. Incorporation of BC impacts soil-water relations, tilth and nutrient status, pH, soil organic matter (SOM), and microbial activity. Soil amendment with BC has been shown to have an overall positive impact on soil health and crop productivity; however, initial soil properties need to be considered prior to the application of BC. There is an urgent need to understand the effects of long-term field application of BC and how it influences the soil microcosm. This knowledge will facilitate predictable enhancement of crop productivity and meaningful carbon sequestration.
Sun, 17 May 2020
REVIEW | doi:10.20944/preprints202005.0284.v1
Subject: Life Sciences, Other Keywords: hypoxia; HIF-1α; partial EMT; collective migration; inflammatory breast cancer; E-cadherin; metastasis
Online: 17 May 2020 (08:19:42 CEST)
Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.
REVIEW | doi:10.20944/preprints202005.0283.v1
Subject: Life Sciences, Other Keywords: fat replacer; octenyl succinic anhydride; OSA starch; starch properties
Online: 17 May 2020 (08:14:12 CEST)
Along with the rapid development of the trend in the health sector, various studies have been conducted to find alternative healthier foods, one of which is reducing fat consumption. Currently, many researchers focus on one of modified starches that can be utilized as a fat replacer is starch modified with OSA (octenyl succinic anhydride). In the last decade, there have been quite a lot of publications related to OSA starch, further the number is still increasing. This review discusses the synthesis method of OSA starch and its optimization, functional characteristics, and its application to be a fat replacer in many kinds of products daily consumed. Various pre-treatment methods could be applied to create OSA starch which has higher degree of substitution values. The presence of conjugate bonds with the OSA group in starch polymers could produce very amphiphilic starch characteristic so as to have an emulsifying function. Emulsions shaped from OSA starch were utilized as fat replacers in foods with high level of fat content. Partial OSA starch substitution was successfully utilized as a fat replacer for several types of food products with similar sensory attributes or even slightly better than the native product. The resulting product could be defined as a healthier choice because it had relatively lower fat and calorie content. Even so, adjustments through further study are still needed so that the food produced is able to have a higher level of sensory acceptance relative to native food without fat substitution.
Thu, 14 May 2020
REVIEW | doi:10.20944/preprints202005.0235.v1
Subject: Life Sciences, Other Keywords: strap muscle invasion; prognosis; differentiated thyroid carcinoma; meta-analysis; review
Online: 14 May 2020 (11:35:41 CEST)
Gross strap muscle invasion (gSMI) in patients with differentiated thyroid cancer (DTC) was defined as high-risk recurrent group in the 2015 American Thyroid Association guidelines. However, controversy persists because several studies suggested gSMI had little effect on disease outcome. Herein, a systematic review and meta-analysis was conducted to investigate impact of gSMI on outcome of DTC. Methods: A systematic search of electronic databases (PubMed, EMBASE, Cochrane Library, and MEDLINE) for studies published until February 2020 was performed. Case-control studies and randomized controlled trials that studied the impact of gSMI on outcome of DTC were included. Results: Six studies (all retrospective studies) involving 13639 patients met final inclusion criteria. Compared with no extrathyroidal extension (ETE), patients with gSMI were associated with increased risk of recurrence (P=0.0004,OR, 1.46; 95% CI: 1.18 to 1.80) and lymph node metastasis (LNM) (P<0.00001,OR 4.19;95% CI. 2.53 to 6.96). For mortality (P=0.34,OR 1.47;95% CI:0.67 to 3.25), ten-year disease-specific survival (P=0.80, OR 0.91;95% CI:0.44 to 1.88) and distant metastasis (DM) (P=0.21, OR 2.94;95% CI. 0.54 to 15.93), there was no significant difference between gSMI and no ETE group. In contrast with maximal ETE, patients with gSMI were associated with decreased risk of recurrence (P<0.0001,OR, 0.58; 95% CI: 0.44 to 0.76) , mortality (P=0.0003,OR 0.20;95% CI:0.08 to 0.48), LNM (P=0.0003,OR 0.64;95% CI. 0.50 to 0.81) and DM (P=0.0009,OR 0.28;95% CI. 0.13 to 0.59). Conclusions: DTC patients with gSMI had a higher risk of recurrence and LNM than those without ETE. However, in contrast with maximal ETE, a much better prognosis was observed in DTC patients with only gSMI. The findings of our meta-analysis provide supportive evidence for the validity of the T category changes in the 8th edition American Joint Committee on Cancer system. The actual impact of gSMI should be re-evaluated and revised in the recurrent risk stratification system in the future.
CONCEPT PAPER | doi:10.20944/preprints201910.0311.v2
Online: 14 May 2020 (08:52:09 CEST)
Technological advances made Virtual and Mixed Reality (VMR) accessible at our fingertips. However, only recently VMR has been explored for the teaching of biology. Here, we highlight how VMR applications can be useful in biology education, discuss about caveats related to VMR use that can interfere with learning, and look into the future of VMR applications in the field. We then propose that the combination of VMR with Machine Learning and Artificial Intelligence can provide unprecedented ways to visualise how species evolve in self-sustained immersive virtual worlds, thereby transforming VMR from an educational tool to the centre of biological interest.
Sat, 9 May 2020
Subject: Life Sciences, Other Keywords: Sars-CoV-2; homology modelling; envelope membrane glycoprotein; Bat; Pangolin; Sars-CoV
Online: 9 May 2020 (08:43:08 CEST)
The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.
Thu, 7 May 2020
ARTICLE | doi:10.20944/preprints202005.0135.v1
Subject: Life Sciences, Other Keywords: Coronavirus disease 2019 (COVID-19); Oral and maxillofacial; Urgency and emergency;
Online: 7 May 2020 (15:29:53 CEST)
The World Health Organization has defined the outbreak of the new coronavirus as a public health emergency of international concern. The average age of patients affected by the disease caused by the virus ranges from 49 to 59 years. The symptoms of coronavirus disease 2019 (COVID-19) infection include fever, cough, acute respiratory disease, and, in severe cases, the disease may progress to pneumonia and renal failure that may lead to death. Many oral and maxillofacial hospital procedures produce aerosol and droplets contaminated by blood, bacteria, and viruses. The purpose of this study is to gather recommendations from health authorities and scientific articles in order to educate surgeons regarding the procedures to assist and treat in oral and maxillofacial surgeries. The objective is to prevent the transmission of COVID-19 during the treatment of patients in urgent and emergency situations. The study’s methodology used the guidelines provided by the Brazilian College of Oral and Maxillofacial Surgery, in addition to the recommendations and epidemiologic data from national and international health authorities. The implementation of special precautions in oral and maxillofacial surgeries may elucidate questions related to the transmission of the disease by asymptomatic carriers and help control the spread of the virus.
COMMUNICATION | doi:10.20944/preprints202005.0132.v1
Subject: Life Sciences, Other Keywords: risk perception; coronavirus; covid-19; risk communication; global health
Online: 7 May 2020 (15:12:32 CEST)
The ongoing COVID-19 pandemic is shaking the foundations of public health governance all over the world. Researchers are challenged by informing and supporting authorities on acquired knowledge and practical implications. This commentary applies established theories of risk perception research to COVID-19 and reflects on the role of risk perceptions in these unprecedented times. Moreover, it calls for utilizing the knowledge on risk perception to improve health risk communication, build trust and contribute to a collaborating governance.
HYPOTHESIS | doi:10.20944/preprints202005.0109.v1
Online: 7 May 2020 (08:18:28 CEST)
Most large fibers in central nervous system of vertebrates are decussated. The cause or the evolutionary force of this phenomenon is not convincingly described. Here we show a pattern for this nervous system property that simultaneously is found to a more basic rule in evolution.The idea here is the "function to anatomy" theorem. We claim that functions of physical, biochemical, enzymatic, etc., in lower scale of living organisms "emerge" to anatomy in larger scales. And reversely, the anatomy we see in multicelular organisms are/were functions in microscopic scales.We propose descriptions, predictions, and a probable road map to what this can implicate in biological and medical issues.
Sun, 3 May 2020
ARTICLE | doi:10.20944/preprints202005.0026.v1
Subject: Life Sciences, Other Keywords: coronavirus; SARS-CoV-2; Spike protein; Nucleocapsid protein; MSA
Online: 3 May 2020 (06:27:36 CEST)
SARS-CoV-2 is a novel and highly pathogenic coronavirus, which was first diagnosed in Wuhan city, China, in 2019, and spread to 185 countries and territories, and as of April 29, 2020, more than 3.11 million cases were recorded, and more than 217,000 people were killed. Despite all worldwide efforts, there is currently no vaccine, any drugs available to protect people against deadly SARS-CoV-2 coronavirus. The world urgently needs a SARS-CoV-2 coronavirus vaccine or effective antiviral drugs to relieve the human suffering associated with the pandemic that kills thousands of people every day. The SARS-CoV-2 genome encode a non-structural proteins named as ORF1a/b, and structural proteins such as spike (S) glycoprotein, nucleocapsid protein (N), small envelop protein (E) and matrix protein (M). A number of studies have been shown that CoV spike (S) glycoprotein and nucleocapsid protein (N) could be promising targets for vaccine, antibodies and therapeutic drug development to combat with deadly, pandemic SARS-CoV-2. Purposes of the present paper is the sequence analysis and amino acid variations of structural proteins deduced from novel coronavirus SARS-CoV-2 strains, isolated in different countries. Multiple sequence alignment of S, N and E proteins from four different coronavirus species, are also described. It is expected that the data from these studies will be very useful for the the designing and development of vaccines, antibodies and therapeutic agents that can be used to combat with the highly pathogenic SARS-CoV-2 coronavirus worldwide.
Sat, 2 May 2020
SHORT NOTE | doi:10.20944/preprints202005.0023.v1
Subject: Life Sciences, Other Keywords: Invasive Alien Species; Guadeloupe; Geoplanidae; Platydemus manokwari; Citizen Science
Online: 2 May 2020 (16:44:46 CEST)
The land flatworm Platydemus manokwari (Platyhelminthes, Geoplanidae) is recorded for the first time from the island of Guadeloupe (French West Indies) in the Caribbean arc. Photographs and records were obtained from citizen science and ranged from the end of 2018 to 2020; specimens were deposited in the collections of the Muséum National d'Histoire Naturelle in Paris, France. This is the first record in Guadeloupe and the second for an island in the Caribbean, after Porto Rico.
SHORT NOTE | doi:10.20944/preprints202005.0017.v1
Online: 2 May 2020 (15:54:19 CEST)
Maximum entropy production principle (MEPP) has been formulated in the mid-twentieth century, and today it has acquired the status of an important principle of science, which is extremely effective in considering various non-equilibrium problems. In this study, for the first time, definition of life is based on an easily measurable physical quantity that is entropy production. Life and evolution are discussed from the point of view of MEPP and the Universe, but not a human
Thu, 30 April 2020
ARTICLE | doi:10.20944/preprints202004.0549.v1
Subject: Life Sciences, Other Keywords: Boron Neutron Capture Therapy; Relative biological effectiveness; thermal neutrons
Online: 30 April 2020 (22:43:49 CEST)
The experimental determination of the relative biological effectiveness of thermal neutron factors is fundamental in Boron Neutron Capture Therapy. Present values have been obtained using mixed beams consisting of both neutrons and photons of various energies. A common weighting factor has been used for both thermal and fast neutron doses, although such an approach has been questioned. At the nuclear reactor of the Institut Laue-Langevin a pure low-energy neutron beam has been used to determine thermal neutron relative biological effectiveness factors. Different tumor cell lines, corresponding to glioblastoma, melanoma, and head and neck squamous cell carcinoma, and non-tumor cell lines (lung fibroblast and embryonic kidney) have been irradiated using an experimental arrangement designed to minimise neutron-induced secondary gamma radiation. Additionally, the cells were irradiated with photons at a medical linear accelerator, providing reference data for comparison with that from neutron irradiation. Survival and proliferation were studied after irradiation, yielding the Relative Biological Effectiveness corresponding to the damage of thermal neutrons for the different tissue types.
Fri, 24 April 2020
ARTICLE | doi:10.20944/preprints202004.0434.v1
Subject: Life Sciences, Other Keywords: higher education; pedagogy; forensic science; VR; learning technologies; crime scene
Online: 24 April 2020 (10:13:58 CEST)
Simulated crime scene investigation is an essential component of forensic science education, but its implementation poses challenges relating to cost, accessibility and breadth of experience. Virtual reality (VR) is an emerging technology which offers exciting prospects for teaching and learning, especially for imparting practical skills. We document here a multidisciplinary experimental study in which a bespoke VR crime scene app was designed and implemented, after which it was tested by both undergraduate student and staff/postgraduate student cohorts. Through both qualitative and quantitative analyses, we demonstrate that VR applications support learning of practical crime scene processing skills. VR-based practical sessions have the potential to add value to forensic science courses through offering cost-effective practical experience and the ability to work in isolation, in a variety of different scenarios. Both user groups reported high levels of satisfaction with the process and reports of adverse effects (motion sickness) were minimal. With reference to user feedback, we proceed to evaluate the scalability and development challenges associated with large-scale implementation of VR as an adjunct to forensic science education.
ARTICLE | doi:10.20944/preprints202004.0422.v1
Subject: Life Sciences, Other Keywords: extravirgin olive oil; cryogen; Citrus genus; phytochemical; nutraceutical value; Citrus x aurantium; Citrus limon; cardiovascular protection
Online: 24 April 2020 (03:03:29 CEST)
Recently the use of food by products as natural sources of biologically active substances has been extensively investigated especially for the development of functional foods fortified with natural antioxidants. Due to their content of bioactive compounds, such as carotenoids, flavonoids and limonoids, Citrus peels could be suitable to formulate enriched olive oils able to boost a healthy nutrition. The aim of this study was: (i) to determine the compositional and sensory profiles of the Citrus olive oil and (ii) to evaluate its nutraceutical properties in rats with high fat diet-induced-metabolic syndrome and oxidative stress. The results obtained show the potential of using the Citrus peels as a source of bioactive compounds to improve the sensory profile as well as the phytochemical composition of olive oil. We demonstrated that the production system of C. aurantium olive oil and C. limon olive oil improves their organoleptic properties without altering their beneficial effects, which, like control extra virgin olive oil, showed protective effects on glucose and serum lipid levels, metabolic activity of adipocytes, myocardial tissue functionality, oxidative stress markers and endothelial function at blood vessel level.
Thu, 23 April 2020
REVIEW | doi:10.20944/preprints202004.0402.v1
Online: 23 April 2020 (04:35:27 CEST)
In the same manner that there are several statements of the second law of thermodynamics but all of them are equivalent, it is possible that most of the entropic methods applied to the nervous system and brain in particular share a similar outcome, or essence, that help understand some aspects of the structure of cognition. In this short review focused on certain aspects of the entropic metrics some results are examined that indicate the fundamental importance of the natural tendency towards a maximal energy distribution for brain activity to be optimal and thus cognition to emerge.
Tue, 21 April 2020
Subject: Life Sciences, Other Keywords: systematic review; cannabis; neuroimaging; age-of-onset psychosis; psychosis; schizophrenia
Online: 21 April 2020 (10:23:52 CEST)
Acute exposure to cannabis has been associated with an array of cognitive alterations, increased risk for neuropsychiatric illness, and other neuropsychiatric sequelae including the emergence of acute psychotic symptoms. However, the mechanisms by which cannabis exposure induces these behavioral and clinical phenotypes remain disputed. To this end, neuroimaging can be a powerful technique to non-invasively study the impact of cannabis exposure on brain structure and function in both humans and animal models. The purpose of the present review is to: 1) provide an update on the findings of pharmacological neuroimaging studies examining the effects of cannabinoids and 2) focus the discussion on studies that examine the sensitive window for the emergence of psychosis. Curren literature indicates that cannabis exposure has varied effects on the brain, with the principal compounds in cannabis (delta-9-tetrahydrocannabinol and cannabidiol) both increasing and decreasing activity in various areas. There are gaps in the literature, especially regarding sex-dependent responses and long-term effects of chronic exposure.
CASE REPORT | doi:10.20944/preprints202004.0384.v1
Subject: Life Sciences, Other Keywords: SARS-CoV-2; COVID-19; Bangladesh; Pandemic; stimulus package
Online: 21 April 2020 (09:34:19 CEST)
An outbreak of a pandemic COVID-19 disease caused by a novel coronavirus SARS-CoV-2 has posed a serious threat to human health and the economy of the whole world. Bangladesh is one of the most densely populated countries in the world, which has also come under the attack of this viral disease. This perspective report aimed to describe the responses of Bangladesh to tackle the COVID-19, particularly on how Bangladesh is dealing with this novel viral disease with limited resources. The first case of a COVID-19 patient was detected in Bangladesh on March 8, 2020. Since then, a total of 2,144 peoples are officially reported as COVID-19 infected with 84 deaths. To combat the COVID-19, the government has taken various steps to tackle the epidemic outbreak of it such as diagnosis of the suspected cases, quarantine of doubted people and isolation of infected patients, local or regional lockdown, grant general leave from all offices for staying home of people, increase public awareness and enforce social distancing and so on. In addition, to address the socio-economic situations, the government announced several financial stimulus packages of about USD 11.17 billion. However, very limited diagnostic facilities, health workers, resources such as hospital beds, personal protective equipment, intensive care unit, and ventilators in the hospitals along with limited public unawareness are the major challenges for Bangladesh to tackle the situation effectively. This report described the responses of Bangladesh to tackle the COVID-19 and discusses prevailing challenges to mitigate this highly contagious disease with limited resources.
Sun, 19 April 2020
REVIEW | doi:10.20944/preprints202003.0076.v2
Online: 19 April 2020 (08:06:38 CEST)
Salamanders have been habitual residents of research laboratories for more than a century, and their history in science is tightly interwoven with vision research. Nevertheless, many vision scientists – even those working with salamanders – may be unaware of how much our knowledge about vision, and particularly the retina, has been shaped by studying salamanders. In this review, we take a tour through the salamander history in vision science, highlighting the main contributions of salamanders to our understanding of the vertebrate retina. We further point out specificities of the salamander visual system and discuss the perspectives of this animal system for future vision research.
HYPOTHESIS | doi:10.20944/preprints202003.0419.v3
Subject: Life Sciences, Other Keywords: origin of genetic codes; ATP-hypothesis; solar energy driven synthesis of chemicals; informatization; structuralization
Online: 19 April 2020 (04:00:24 CEST)
The origin of the genetic code is the key to revealing the origin of life on Earth, as it is a prerequisite for the existence of life. More than half a century has passed since the discovery of the genetic code, but its origin is still one of the greatest mysteries. Is the origin of the genetic code truly unknowable? Does the code truly require external design? Here, a hypothesis is proposed, according to which ATP is at the origin of the genetic code by its coevolution with the pristine biochemical system. ATP has several properties that make it suitable as a plausible initiator of the genetic code. First, ATP is the only energetic product of photosynthesis. Second, ATP is at the heart of the extant biochemical systems. Third, ATP serves as a carrier of both energy and information. Fourth, ATP could energetically elongate chains of both polynucleotides and polypeptides, thus providing a bridge between these molecules and eventually mediating prebiotic biochemical innovation from energy transformation to informatization. This hypothesis shows how primitive life emerged through a series of processes from energy to information flow mediated by ATP. Informatization (processes for creating and managing information) was inevitably coupled with structuralization (processes for organizing or incorporating cellular structures), cyclizing polynucleotides and polypeptides into a feedback loop of reciprocal causation. The triplet codon might be only for stereochemical handling of amino acids through, e.g., Watson–Crick pairing interactions. It is only the evolutionary completion of the genetic code from RNA to DNA that, contrary to the central dogma, marked the dawn of cellular life, when Darwinian evolution began to operate. The ATP hypothesis sheds light on the origin of life, together with the formation of both photosynthetic and biochemical systems, which remains largely unknown thus far.
ARTICLE | doi:10.20944/preprints202004.0318.v1
Subject: Life Sciences, Other Keywords: Alzheimer’s disease; amyloid β; β-secretase; bax; caspase; lamiaceae; mint; oxidative stress
Online: 19 April 2020 (03:57:56 CEST)
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that develops as a consequence of different factors such as oxidative stress and accumulation of the protein amyloid β (Aβ) in the brain, resulting in apoptosis of neuronal cells. The search for a treatment for this disorder is essential as current medications are limited to alleviating symptoms and palliative effects. The aim of this study is to investigate the effects of mint extracts on selected mechanisms implicated in the development of AD. To enable a thorough investigation of mechanisms, including effects on -secretase (the enzyme the leads to the formation of A), on Aβ aggregation, and on oxidative stress and apoptosis pathways, a neuronal cell model, SH-SY5Y cells was selected. Six Mentha taxa were investigated for their in vitro β-secretase (BACE) and Aβ-aggregation inhibition activities. Also, their neuroprotective effects on H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells were evaluated through caspase activity. Real-time PCR and Western blot analysis were carried out for the two most promising extracts to determine their effects on signalling pathways in SH-SY5Y cells. All mint extracts had strong BACE inhibition activity. M. requienii extracts showed excellent inhibition of Aβ-aggregation, while other extracts showed moderate inhibition. M. diemenica and M. requienii extracts lowered caspase activity. Exposure of SH-SY5Y cells to M. diemenica extracts resulted in a decrease in the expression of pro-apoptotic protein, Bax, and an elevation in the anti-apoptotic protein, Bcl-xL, potentially mediated by down-regulation of ASK1-JNK pathway. These results indicate that mint extracts could prevent the formation of Aβ and also could prevent their aggregation if they had already formed. M. diemenica and M. requienii extracts have potential to suppress apoptosis at the cellular level. Hence, mint extracts could provide a source of efficacious compounds for a therapeutic approach for AD.
Thu, 16 April 2020
COMMUNICATION | doi:10.20944/preprints202004.0253.v1
Subject: Life Sciences, Other Keywords: Genomic Epidemiology; GenomeTrakr; microbial pathogen surveillance, NCBI submission; whole genome sequencing; QA/QC; One Health
Online: 16 April 2020 (05:26:42 CEST)
The holistic approach of One Health, which sees human, animal, plant, and environmental health as a unit, rather than discrete parts, requires not only interdisciplinary cooperation, but standardized methods for communicating and archiving data, enabling participants to easily share what they have learned and allow others to build upon their findings.Ongoing work by NCBI and the GenomeTrakr project illustrates how open data platforms can help meet the needs of federal and state regulators, public health laboratories, departments of agriculture, and universities. Here we describe how microbial pathogen surveillance can be transformed by having an open access database along with Best Practices for contributors to follow. First, we describe the open pathogen surveillance framework, hosted on the NCBI platform. We cover the current community standards for WGS quality, provide an SOP for assessing your own sequence quality and recommend QC thresholds for all submitters to follow. We then provide an overview of NCBI data submission along with step by step details. And finally, we provide curation guidance and an SOP for keeping your public data current within the database. These Best Practices can be models for other open data projects, thereby advancing the One Health goals of Findable, Accessible, Interoperable and Re-usable (FAIR) data.
Wed, 15 April 2020
REVIEW | doi:10.20944/preprints202004.0242.v1
Subject: Life Sciences, Other Keywords: extracellular vesicles; stem cells; induced pluripotent stem cells (iPSCs); regenerative medicine
Online: 15 April 2020 (10:08:44 CEST)
Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.
ARTICLE | doi:10.20944/preprints202004.0232.v1
Online: 15 April 2020 (09:10:49 CEST)
Laminopathies are causally associated with mutations on Lamin A gene (LMNA). To date, more than 400 mutations in LMNA have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range of phenotypes. Unfortunately, little is known about the mechanisms underlying the effect of the majority of these mutations. This is the case of more than 40 mutations that are located at exon 4. Using CRISPR/Cas9 technology, we have generated a collection of Lmna exon 4 mutants in mouse C2C12 myoblasts. These cell models include different types of exon 4 deletions and the presence of R249W mutation, one of the human variants associated with a severe type of laminopathy (LMNA-associated congenital muscular dystrophy). We have characterized these clones by measuring their nuclear circularity, myogenic differentiation capacity in 2D and 3D conditions, DNA damage, and p-ERK and p-AKT levels. Our results indicate that Lmna exon 4 mutants show abnormal nuclear morphology. In addition, levels and/or subcellular localization of different members of the lamin and LINC complex are altered in all these mutants. Whereas no significant differences were observed for ERK and AKT activities, the accumulation of DNA damage was associated to the Lmna p.R249W mutant myoblasts. Finally, significant myogenic differentiation defects were detected in the Lmna exon 4 mutants. These results have key implications in the development of future therapeutic strategies for the treatment of laminopathies.
Mon, 13 April 2020
ARTICLE | doi:10.20944/preprints202004.0211.v1
Subject: Life Sciences, Other Keywords: prediction; model; risk score; low birthweight; pregnant women; decision curve analysis
Online: 13 April 2020 (11:15:32 CEST)
At least one ultrasound is recommended to predict fetal growth restriction and low birthweight earlier in pregnancy. However, in low-income countries imaging equipment and trained manpower are scarce. Hence, we developed and validated a model and risk score to predict low birthweight using maternal characteristics during pregnancy, for use in resource limited settings. We conducted a prospective cohort study among 379 pregnant women in South Ethiopia. A step-wise multivariable analysis was done to develop the prediction model. To improve clinical utility, we developed a simplified risk score to classify pregnant women at high- or low-risk of low birthweight. The accuracy of the model was evaluated using the area under the receiver operating characteristics curve (AUC) and calibration plot. We evaluated the clinical impact of the model using a decision curve analysis across various threshold probabilities. Age at pregnancy, underweight, anemia, height, gravidity, and presence of comorbidity remained in the final multivariable prediction model. The area under the receiver operating characteristics curve (AUC) of the model was 0.83 (95% confidence interval: 0.78 to 0.88). The decision curve analysis shows the model provides a higher net benefit across ranges of threshold probabilities. In general, this study showed the possibility of predicting low birthweight using maternal characteristics during pregnancy. The model could help to identify those at higher risk of having a low birthweight baby. This feasible prediction model would offer an opportunity to reduce obstetric-related complications and thus improving the overall maternal and child healthcare in low- and middle-income countries.
Thu, 9 April 2020
HYPOTHESIS | doi:10.20944/preprints202004.0153.v1
Subject: Life Sciences, Other Keywords: Severe acute respiratory syndrome coronavirus 2; 2019-nCoV; COVID-19; angiotensin converting enzyme 2; Receptor; Live Attenuated Oral Vaccine; Intestine; proximal and distal enterocytes; herd immunity
Online: 9 April 2020 (13:10:50 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.
Tue, 7 April 2020
SHORT NOTE | doi:10.20944/preprints202004.0089.v1
Subject: Life Sciences, Other Keywords: Sars-CoV-2; Homology modelling; Envelope Membrane glycoprotein; Bat; Pangolin; Sars-CoV
Online: 7 April 2020 (11:09:23 CEST)
The Coronavirus disease (COVID-19) is a new viral infection caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) that was initially reported in city of Wuhan, China and afterwards spread globally. Genomic analyses revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) Pangolin and Bat coronavirus specific isolates. In this study we focused on two proteins of Sars-CoV-2 surface: Envelope protein and Membrane protein. Sequences from Sars-CoV-2 isolates and other closely related virus were collected from the GenBank through TBlastN searches. The retrieved sequences were multiply aligned with MAFFT. The Envelope protein is identical to the counterparts from Pangolin CoV MP798 isolate and Bat CoV isolates CoVZXC21, CoVZC45 and RaTG13. However, a substitution at position 69 where an Arg replace for Glu, and a deletion in position 70 corresponding to Gly or Cys in other Envelope proteins were found. The Membrane glycoprotein appears more variable with respect to the SARS CoV proteins than the Envelope: a heterogeneity at the N-terminal position, exposed to the virus surface, was found between Pangolin CoV MP798 isolate and Bat CoV isolates CoVZXC21, CoVZC45 and RaTG13. Mutations observed on Envelope protein are drastic and may have significant implications for conformational properties and possibly for protein-protein interactions. Mutations on Membrane protein may also be relevant because this protein cooperates with the Spike during the cell attachment and entry. Therefore, these mutations may influence interaction with host cells. The mutations that have been detected in these comparative studies may reflect functional peculiarities of the Sars-CoV-2 virus and may help explaining the epizootic origin the COVID-19 epidemic.
Fri, 3 April 2020
REVIEW | doi:10.20944/preprints202004.0019.v2
Online: 3 April 2020 (15:23:50 CEST)
OBJECTIVE: Recent worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of respiratory coronavirus disease 2019 (COVID-19), is a current, ongoing life-threatening crisis and international public health emergency. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2.MATERIALS AND METHODS: A broad search of the literature was performed in “PubMed” “Medline” “Web of knowledge”, and “Google Scholar” World Health Organization-WHO” using the keywords “severe acute respiratory syndrome coronavirus”, “2019-nCoV”, “COVID-19, “SARS”, “SARS-CoV-2” “Epidemiology” “Transmission” “Pathogenesis” “Clinical Characteristics”. We reviewed and documented the information obtained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection.RESULTS: The global cases of COVID-19 as of April 2, 2020 have risen to more than 900,000 and morbidity has reached more than 47,000. The incidence rate for COVID-19 has been predicted to be higher than the previous outbreaks of other coronavirus family members, including those of SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation of SARS-CoV-2 infection ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness.Individuals at higher risk for severe illness include elderly people and patients with a weakened immune system or that are suffering from a underlying chronic medical condition like hypertension, diabetes, cancer, respiratory illness or cardiovascular diseases.CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, currently affecting 170 countries and territories across the globe. There is still much to be understood regarding SARS-CoV-2 about its virology, epidemiology and clinical management strategies; this knowledge will be essential to both manage the current pandemic and to conceive comprehensive measures to prevent such outbreaks in the future.
Thu, 2 April 2020
REVIEW | doi:10.20944/preprints202004.0019.v1
Online: 2 April 2020 (12:20:19 CEST)
OBJECTIVE: Recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), another member of coronavirus family is an ongoing worldwide life-threatening crisis. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2. MATERIALS AND METHODS: A broad search of the literature was performed in “PubMed” “Medline” “Web of knowledge”, and “Google Scholar” World Health Organization-WHO” using the key words “severe acute respiratory syndrome coronavirus”, “SARS”, “SARS-CoV-2” “Epidemiology” “Transmission” “Pathogenesis” “Clinical Characteristics”. We reviewed and documented the information attained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection. RESULTS: The global cases of COVID-19 till 30th March 2020 have rose more than 700,000 and morbidity has gone more than 37,000. The infection rate for COVID-19 has been predicted to be higher than the previous outbreaks of same family members, that includes the SARS-CoV and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness. High risk includes elderly people and patients with weak immune system or suffering from chronic medical condition like hypertension, diabetes, cancer, respiratory illness and cardiovascular diseases. CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, affecting almost each and every country on globe. As there is still growing understanding of SARS-CoV-2 in relation to its virology, epidemiology and clinical management strategies, we need to learn our lessons to conceive comprehensive measures to prevent such outbreaks in future.
ARTICLE | doi:10.20944/preprints202004.0016.v1
Subject: Life Sciences, Other Keywords: glaucoma; retina ganglion cell degeneration; microarray; genes coordination; notch signaling pathway; complement cascade
Online: 2 April 2020 (11:59:28 CEST)
Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and applied systems biology approaches to better understand the molecular mechanisms related with the retinal remodeling after induction of RGC degeneration. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Enrichment analysis showed that Complement cascade and Notch signaling pathway were the main affected pathways after ONC. To expand our studies of these two pathways, we examined the coordination of gene expressions within each pathway and with the entire transcriptome. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles. This study provided novel findings beyond the regulation of individual gene expression and disclosed changes in the control of expression by Complement cascade and Notch signaling functional pathways important for both RGC degeneration and remodeling of the retinal tissue after ONC.
HYPOTHESIS | doi:10.20944/preprints202003.0419.v2
Subject: Life Sciences, Other Keywords: origin of genetic codes; ATP-hypothesis; solar energy driven synthesis of chemicals; informatization; structuralization
Online: 2 April 2020 (05:16:09 CEST)
The origin of genetic codes is the key to reveal life’s origin on the earth as it is a prerequisite for the existence of life. More than half a century has passed since the discovery of genetic codes, while their origin is still one of the greatest mysteries. Are the origins of genetic codes really unknowable? Do they really require external design? Here, I present an ATP-hypothesis that explains how the genetic codes came into being with the coevolution of biochemical system. ATP has several properties that make it suitable as the initiator of the origin of genetic codes. First, ATP is the only energetic product of photosynthesis. Second, ATP is at the heart of the extant biochemical systems. Third, ATP serves as carriers of both energy and information. Fourth, ATP could energetically elongate chains of both polynucleotides and polypeptides, thus providing a bridge between them, and eventually mediating prebiotic biochemical transaction from energy to information. This hypothesis shows how primitive life emerged through a series of processes from energy to information mediated by ATP. Informatization (processes of creating and managing information) was inevitably coupled with structuralization (processes of organizing or incorporating into a cellular structure), making polynucleotides and polypeptides be cyclized into a system of reciprocal causation. The triplet codon might just be for stereo-chemical handing of amino acid through e.g. Watson–Crick pairing interactions. It is an evolutionary completion for genetic codes from RNA to DNA, only which, a reverse to the Central Dogma, marked the dawn of cellular life when Darwinian evolution began to operate. ATP-hypothesis shades lights on the origin of life, together with the formations of both photosynthesis and biochemical systems, which have been largely unknown so far.
Wed, 1 April 2020
COMMUNICATION | doi:10.20944/preprints202004.0006.v1
Online: 1 April 2020 (09:30:36 CEST)
The novel coronavirus, COVID-19 is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Like millions of others around the world, I am wondering, is there anything that could be done, other than keeping high personal hygiene, and be vigilant of symptoms, to reduce the chances of infection, or at least to reduce the burden of the disease. So far, the National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this opinion-based article, I want to discuss, why keeping the adequate micronutrient balance might enhance the host response and be protective of viral infections. A detailed in-depth discussion of various micronutrients is not the purpose of this article, I will mostly emphasize on the role of zinc in viral infection.
Sun, 29 March 2020
ARTICLE | doi:10.20944/preprints202003.0429.v1
Subject: Life Sciences, Other Keywords: Blumeria graminis; hexaploid bread wheat; Magnaporthe oryzae; Mlo; plant disease resistance; powdery mildew; TALEN; TILLING; Zymoseptoria tritici
Online: 29 March 2020 (09:10:52 CEST)
Barley mlo mutants are well known for their profound resistance against powdery mildew disease. Recently, mlo mutant plants were generated in hexaploid bread wheat (Triticum aestivum) with the help of transgenic (transcription-activator-like nuclease, TALEN) and non-transgenic (targeted induced local lesions in genomes, TILLING) biotechnological approaches. While full gene knockouts in the three wheat Mlo (TaMlo) homoeologs, created via TALEN, confer full resistance to the wheat powdery mildew pathogen (Blumeria graminis f.sp. tritici), the currently available TILLING-derived Tamlo missense mutants provide only partial protection against powdery mildew attack. Here we studied the infection phenotypes of TALEN- and TILLING-derived Tamlo plants to the two hemibiotrophic pathogens Zymoseptoria tritici, causing Septoria leaf blotch in wheat, and Magnaporthe oryzae pv. Triticum (MoT), the causal agent of wheat blast disease. While Tamlo plants showed unaltered outcomes upon challenge with Z. tritici, we found allele-specific levels of enhanced susceptibility to MoT, with stronger powdery mildew resistance correlated with more invasive growth by the blast pathogen. Surprisingly, unlike barley mlo mutants, young wheat mlo mutant plants do not show undesired pleiotropic phenotypes such as spontaneous callose deposits in leaf mesophyll cells or signs of early leaf senescence. In conclusion, our study provides evidence for allele-specific levels of enhanced susceptibility of Tamlo plants to the hemibiotrophic wheat pathogen MoT.
HYPOTHESIS | doi:10.20944/preprints202003.0419.v1
Subject: Life Sciences, Other Keywords: origin of genetic codes; ATP-hypothesis; solar energy driven synthesis of chemicals; informatization; structuralization
Online: 29 March 2020 (04:08:22 CEST)
The origin of genetic codes is the key to reveal life’s origin on the earth as it is a prerequisite for the existence of life. More than half a century has passed since the discovery of genetic codes, while their origin is still one of the greatest mysteries. Are the origins of genetic codes really unknowable? Do they really require external design? Here, we present an ATP-hypothesis that explains how the genetic codes came into being with the coevolution of biochemical system. ATP has several properties that make it suitable as the initiator of the origin of genetic codes. First, ATP is the only energetic product of photosynthesis. Second, ATP is at the heart of the extant biochemical systems. Third, ATP serves as carriers of both energy and information. Fourth, ATP could energetically elongate chains of both polynucleotides and polypeptides, thus providing a bridge between them, and eventually mediating prebiotic transaction from energy to information. This hypothesis shows how primitive life emerged through a series of processes from energy to information. Informatization (processes of creating and managing information) was inevitably coupled with structuralization (processes of organizing or incorporating into a cellular structure), making polynucleotides and polypeptides be cyclized into a system of reciprocal causation. The triplet codon might just be for stereo-chemical handing of amino acid through e.g. Watson–Crick pairing interactions. This hypothesis shades lights on the origin of life, together with the formations of both photosynthesis and biochemical systems, which have been largely unknown so far.
Tue, 24 March 2020
REVIEW | doi:10.20944/preprints202003.0362.v1
Online: 24 March 2020 (14:46:29 CET)
With the current rapid spread of COVID-19, global health systems are increasingly overburdened by the sheer number of people that need diagnosis, isolation and treatment. Shortcomings are evident across the board, from staffing, facilities for rapid and reliable testing to availability of hospital beds and key medical-grade equipment. The scale and breadth of the problem calls for an equally substantive response not only from frontline workers such as medical staff and scientists, but from skilled members of the public who have the time, facilities and knowledge to meaningfully contribute to a consolidated global response. Here, we summarise community-driven approaches based on Free and Open Source scientific and medical Hardware (FOSH) currently being developed and deployed to bolster access to personal protective equipment (PPE), patient treatment and diagnostics.
Mon, 23 March 2020
HYPOTHESIS | doi:10.20944/preprints202003.0042.v2
Subject: Life Sciences, Other Keywords: Flue; Virus; COVID19; SARS CoV-2; Spike Protein; Virtual Screening; dgitoxin; anthracycline; rolitetracycline; E-155
Online: 23 March 2020 (10:19:17 CET)
The novel coronavirus (SARS-CoV-2) is a human pathogen recently emerged in China, causing a global pandemic of severe respiratory illness (COVID19). SARS-CoV-2 makes entry into human cells through its spike (S) protein that binds to cell surface receptors. Widespread of SARS-CoV-2 has been attributed to high affinity of S protein to its receptor. A homology model of the receptor binding domain of SARS-CoV-2 S protein (RBD) was built. RBD- receptor docking and published molecular dynamics data were used to map the key RBD-receptor interaction hotspot (RBDhp) on the RBD. Primary virtual screening was carried out against RBDhp using more than 3300 compounds approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Compounds that bind to hpRBD with a binding energy ≤ - 6.5 kcal/mol were subjected to secondary screening using a recently published cryo EM (2.9 Å) structure of RBD. A cardiac glycoside (dgitoxin), two anthracyclines (zorubicin and aclarubicin), a tetracycline derivative (rolitetracycline), a cephalosporin (cefoperazone) and a food dye (E-155) were predicted to be most potent inhibitors of RBD – receptor interaction. An anti-asthmatic drug (zafirlukast) and several other drugs (itrazol, fazadinium, troglitazone, gliquidone, Idarubicin, Oxacillin) were found to be high affinity binders that may have a potential to inhibit RBD – receptor interaction.
Wed, 18 March 2020
REVIEW | doi:10.20944/preprints202003.0288.v1
Subject: Life Sciences, Other Keywords: surveying microglia; amoeboid microglia; P2X receptors; P2Y receptors; P1 receptors; CD39; CD73; microglia-neuron cross talk; phagocytosis; microglial products; neuroinflammation
Online: 18 March 2020 (16:52:28 CET)
Microglial cells, the resident macrophages of the CNS, exist in a process-bearing, ramified/surveying phenotype under resting conditions. Upon activation by cell damaging factors they get transformed to an amoeboid phenotype releasing various cell products including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen/nitrogen species and the excytotoxic ATP and glutamate. In addition, they engulf pathogenic bacteria or cell debris and phagocytose them. However, already resting/surveying microglia has a number of important physiological functions in the CNS; they e.g. shield small disruptions of the blood-brain barrier by their processes, dynamically interact with synaptic structures and clear surplus synapses during development. In neurodegenerative illnesses they aggravate the original disease by a microglia-based compulsory neuroinflammatory reaction. Therefore, the blockade of this reaction improves the outcome of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. The function of microglia is regulated by a whole array of purinergic receptors classified as P2Y12, P2Y6, P2Y4, P2X4, P2X7, A2A, A3, and being targets for endogenous ATP, ADP, or adenosine. ATP is sequentially degraded by the ecto-nucleotidases and 5’-nucleotidase enzymes to the weak adenosine agonist inosine as an end-product. The appropriate selective agonists/antagonists for purinergic receptors as well as the respective enzyme inhibitors may profoundly interfere with microglial functions and reconstitute the homeostasis of the CNS disturbed by neuroinflammation.
Sun, 15 March 2020
COMMUNICATION | doi:10.20944/preprints202003.0234.v1
Subject: Life Sciences, Other Keywords: astrocytes; calcineurin; GLAST; protein synthesis; protein degradation; proteostasis
Online: 15 March 2020 (01:39:55 CET)
Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer’s disease and epilepsy. However, the mechanisms by which GLAST expression is altered are poorly understood. Here we used a combination of pharmacological and genetic approaches coupled with quantitative PCR and Western blot to investigate the mechanism of the regulation of GLAST expression by a Ca2+/calmodulin-activated phosphatase calcineurin (CaN). We show that treatment of cultured hippocampal mouse and fetal human astrocytes with a CaN inhibitor FK506 resulted in a dynamic modulation of GLAST protein expression, being downregulated after 24-48 h, but upregulated after 7 days of continuous FK506 (200 nM) treatment. Protein synthesis, as assessed by puromycin incorporation in neo-synthesized polypeptides, was inhibited already after 1 h of FK506 treatment, while the use of a proteasome inhibitor MG132 (1 μM) shows that GLAST protein degradation was only suppressed after 7 days of FK506 treatment. In astrocytes with constitutive genetic ablation of CaN both protein synthesis and degradation were significantly inhibited. Taken together, our data suggest that, in cultured astrocytes, CaN controls GLAST expression at a posttranscriptional level through regulation of GLAST protein synthesis and degradation.
Thu, 12 March 2020
ARTICLE | doi:10.20944/preprints202003.0216.v1
Subject: Life Sciences, Other Keywords: Aflatoxin treated corn; Aspergillus flavus; atoxigenic aflatoxin; bee community; biological pesticide; saprophytic soil fungus
Online: 12 March 2020 (14:18:11 CET)
A saprophytic soil fungus, Aspergillus flavus, produces aflatoxin (toxigenic strains) in the kernels of corn (Zea mays L.) and seeds of many other crops. Many strains of A. flavus do not produce toxigenic aflatoxin, and soil application of these atoxigenic strains is a suppressive control tactic to assist in controlling toxigenic conspecifics. Effects of atoxigenic A. flavus applications on honey bees (Apis mellifera L.) and other bees are unknown, and basic information on bee occurrences in corn fields treated with and without this biological pesticide is needed to inform integrated pest management in corn. Fields with atoxigenic A. flavus applications were compared to nearby control fields in three counties in corn production regions in eastern Texas. In each corn field, twenty bee bowl traps were deployed along four equal transects located between corn rows, with contents of the bowls (i.e. bees) retrieved after 24 hours. Eleven bee genera from four families were collected from corn fields, with only two honey bees collected and zero honey bees observed in transects. The sweat bee genus Agapostemon (primarily composed of the Texas-striped sweat bee A. texanus) was most abundant in corn fields (44% of the total number of bees collected) followed by long-horned bees (Melissodes spp., 24%). The southernmost county (i.e. San Patricio) produced over 80% of the total number of bees collected. Bee communities occurring in corn production fields with applications of atoxigenic A. flavus applications were not significantly different from nearby control fields. While little is known of bee resource use in corn production systems in Texas, the abundant yet variable bee communities across latitudes in this study suggests a need to investigate the influence of farming practices on bee resources in regional corn production systems.
ARTICLE | doi:10.20944/preprints202003.0215.v1
Subject: Life Sciences, Other Keywords: major depression; skin fibroblasts; mitochondria; bioenergetics; oxidative phosphorylation; adenosine triphosphate; calcium imaging; mitochondrial membrane potential; mitochondrial DNA copy number
Online: 12 March 2020 (14:11:25 CET)
Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial disfunction in adult human skin fibroblasts which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and ATP-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance which is associated with the molecular pathophysiology of MDD. The observed alterations in OXPHOS and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.
Sun, 8 March 2020
ARTICLE | doi:10.20944/preprints202003.0142.v1
Subject: Life Sciences, Other Keywords: total knee arthroplasty; rehabilitation program; knee osteoarthritis; exercise rehabilitation; postoperative care
Online: 8 March 2020 (16:50:41 CET)
This multi-center, single-blinded, randomized controlled study assessed the efficacy of phased exercise rehabilitation programs in patients who underwent a total knee arthroplasty (TKA) and investigated suitable exercise types, intensities, and frequencies for patients undergoing postoperative rehabilitation. Between January and March 2018, 494 patients who had undergone TKA were treated at two medical centers. Patients were randomized and allocated to the rehabilitation group (n=330) or the control group (n=164; treated with postoperative care). The 100-mm Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), range of motion, and Short-Form 36 (SF-36) scores were assessed and compared between the two groups. The average WOMAC score was 84.40±15.20 in the rehabilitation group and 108.30±3.90 in the control group (p=0.009). The mean VAS score was 2.54±0.16 in the rehabilitation group and 2.87±0.31 in the control group (p=0.024). Furthermore, the range of motion was 125.02±6.20 in the rehabilitation group and 116.40±1.40 in the control group (p=0.017). The mean SF-36 score was 105.40±21.50 in the rehabilitation group and 83.70±5.01 in the control group (p=0.043). This study suggests that the phase rehabilitation program could be more effective at improving pain, knee function, and quality of life than condition postoperative care after TKA.
ARTICLE | doi:10.20944/preprints202003.0132.v1
Online: 8 March 2020 (04:40:36 CET)
Body temperature responses were recorded during phases of work (waiting to work in close proximity to search site, active work in a search site, and post-work recovery crated in vehicle) in human remains detection dogs during search training. State or federally certified human remains detection dogs (n = 8) completed eight iterations of searching, rotating through six different types of search environments to detect numerous scent sources including partial and complete, buried, hidden, or fully visible human remains. Internal temperature (Tgi) of the body was measured continuously using an ingestible thermistor in the gastrointestinal tract. Mean total phase times were: waiting to work: 9.17 minutes (± 2.27); active work: 8:58 minutes (± 2:49); and post work recovery: 24:04 minutes (± 10.59). Tgi was impacted by phase of work (P < 0.001) with a small increase during active work, with mean peak temperature 39.4 °C (± 0.34 ºC) during that period. Tgi continued to increase for a mean of 7:37 (± 6:04) minutes into the post-work recovery phase in the handler’s vehicle with a mean peak Tgi of 39.66 °C (± 0.41 ºC). No significant increase in temperature was measured during the waiting to work phase, suggesting anticipation of work did not appear to contribute to overall body temperature increase during the waiting to work recovery cycle. Continued increase of gastrointestinal body temperature several minutes after cessation of exercise indicates that risk of heat injury does not immediately stop when the dog stops exercising, although none of the dogs in this study reached clinically concerning body temperatures or displayed any behavioral signs suggestive of pending heat injury. More work is needed to better understand the impact of vehicle crating on post-work recovery temperatures in dogs.
Thu, 5 March 2020
ARTICLE | doi:10.20944/preprints202003.0078.v1
Online: 5 March 2020 (03:15:43 CET)
Background: Cigarette smoking (CS) is a global public health problem and a high-risk factor for various diseases. In December 2019, a novel coronavirus (HCoV-19) was identified in Wuhan, China. Because ACE2 has been identified as a receptor for HCoV-19, we hypothesize that CS affects the expression pattern of ACE2 in respiratory tract, causing differences in susceptibility to the virus. Methods: Three datasets (GSE994, GSE17913, and GSE18344), were downloaded from the Gene Expression Omnibus (GEO) database. Correlation and enrichment analysis were used to evaluate the function of ACE2. Also, the different expression of ACE2 in different groups of three datasets were analyzed. Results: Genes associated with ACE2 were enriched in important biological processes such as viral processes and immune response. Elevated ACE2 were found in intrapulmonary airways (GSE994) and oral epithelial cells (GSE17913) of smokers but not those of non-smokers or former smokers. Significant dose- and time-dependent relationships between CS and ACE2 expression were observed in mouse lung tissues, and long periods without smoking were found to significantly reduce ACE2 expression. Conclusions: Both human and rat data confirmed that CS could induce increased ACE2 in the respiratory tract, indicating that smokers have a higher susceptibility to HCoV-19.
Wed, 4 March 2020
ARTICLE | doi:10.20944/preprints202003.0056.v1
Subject: Life Sciences, Other Keywords: Hermetia illucens prepupae; Black soldier fly; coffee silverskin; microalgae; toxic metals; bioaccumulation; chemical hazard
Online: 4 March 2020 (09:48:16 CET)
Among other species, Black Soldier Fly (Hermetia illucens, HI, Diptera, Stratiomydae) has the great potential as food and feed ingredient in the EU, particularly thanks to its preference for organic waste as growth substrate. The production of insects as livestock feed or as food ingredient requires a strict monitoring of heavy metal content in the growth substrate in order to secure its safe. This study aims to investigate the presence of toxic metals cadmium, lead, mercury, arsenic, and nickel in HI prepupae and their growth substrates based on coffee roasting by-product and microlagae Schizochytrium sp. and Isochrysis sp. Analyses were carried out via graphite furnace atomic absorption spectrophotometry for Cd, Pb, Ni, and As, and via Direct Mercury Analyzer for Hg. All metal concentrations found in growth substrates were below the legal limit of undesirable substances in animal feed (2002/32/EC). Metals concentrations in HI prepupae were in the range (mg kg-1 wet weight): Cd 0.072–0.084, Pb 0.018–0.026, Hg 0.010–0.032, As 0.036–0.047, Ni 0.18–0.76. HI prepupae accumulate Cd, Pb and Hg, but our results indicate that the risk of exposure to metals from consumption of HI prepupae is relatively low and in compliance with European Union regulations.
Tue, 3 March 2020
REVIEW | doi:10.20944/preprints202003.0044.v1
Subject: Life Sciences, Other Keywords: Apis mellifera; host–parasite relationship; natural selection; resistance; selective breeding; Varroa destructor
Online: 3 March 2020 (11:53:56 CET)
Despite the implementation of control strategies, the invasive parasitic mite Varroa destructor remains one of the principal causes of honey bee (Apis mellifera) colony losses in numerous countries. For this reason, the parasite represents a serious threat to beekeeping and to agro-ecosystems that benefit from the pollination services provided by honey bees. Numerous selection programmes have been initiated over the last three decades with the aim of promoting the establishment of balance in the host–parasite relationship and, thus, helping European honey bees to survive in the presence of the parasite without the need for acaricide treatments. Such programmes have focused on either selective breeding for putative resistance traits or natural selection. To date, no clear overview of these attempts has been available, which has prevented building on past successes or failures and, therefore, hindered the development of a sustainable strategy for solving the V. destructor problem. In the present study, we review past and current selection strategies, report on their outcomes and discuss their limitations. Based on this state-of-the-art knowledge, we propose a strategy for increasing response to selection and colony survival against V. destructor infestations. Developing in-depth knowledge regarding the selected traits, optimising selection programmes and communicating their outcomes are all crucial to our efforts to establish a balanced relationship between the invasive parasite and its new host.
HYPOTHESIS | doi:10.20944/preprints202003.0042.v1
Subject: Life Sciences, Other Keywords: COVID -19; 2019-nCoV; spike (S) protein; zorubicin; aclarubicin
Online: 3 March 2020 (11:41:51 CET)
The novel coronavirus (2019-nCoV) is a human and animal pathogen recently emerged in the city of Wuhan in Hubei province of China, causing a spectrum of severe respiratory illnesses. Corona viruses makes entry in to human cells through its spike (S) protein that binds to cell surface receptors. Wide spread of 2019-nCoV has been attributed to relatively high affinity of S protein to its receptor. Although S protein is a highly importantdrug target, unavailability of a high-resolution crystal structure and solvent accessible binding surface has made it a tedious target for current rapid virtual screening. A homology model of the receptor binding domain (RBD) of 2019 -n CoV S protein that is reasonably acceptable for drug screening was prepared using a high resolution crystal structure of SARS corona virus (SARS CoV)S protein. Data obtained from RBD- receptor docking experiments and published molecular dynamics experiments were used to map a RBD-receptor interaction hotspot that can be used for designing small molecule inhibitors. The hot spot was then used for virtual screening of more than 3000 drugs approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Two anthracycline class drugs (zorubicin and aclarubicin) and a food dye (E 155) were predicted to be potent inhibitors of RBD – receptor interaction. Results of present study provide evidence for the potential of these compounds asprophylactic medications or for use to reduce disease severity of COVID -19.
Sat, 29 February 2020
REVIEW | doi:10.20944/preprints202002.0465.v1
Subject: Life Sciences, Other Keywords: vitamin D; calcium; bone mass; osteoporosis; dairy foods; fortified foods
Online: 29 February 2020 (11:46:01 CET)
Background: Vitamin D and calcium are the most important dietary compounds that affect bone mass, even if other minerals (potassium, zinc, etc.) and other vitamins (A, C and K) are also involved. Vitamin D, in fact, plays an important role in calcium homeostasis and calcium absorption. Talking about calcium, it is well known the “calcium paradox”: hip fractures incidence are higher in western countries, where calcium is frequently included in human diet, while the occurrence of these fractures is lower in developing countries, where diets are normally poor in calcium. This paradox may be partially understood considering vitamin D content in serum of local population; a report produced by WHO/FAO experts team investigating on diet, nutrition and the prevention of specific diseases stated that there is enough clinical data demonstrating that an intake of vitamin D and calcium together sufficient to cover dietary requirements can greatly reduce the risk of osteoporotic fracture in older people. Vitamin D can also act as a hormone; vitamin D2 (ergocalciferol) is derived from the UV-B radiation of ergosterol, the vitamin D precursor naturally found in plants, fungi, and invertebrates. Vitamin D3 (cholecalciferol) is originated by sunlight exposure from 7-dehydrocholesterol, a precursor of cholesterol that can also act as a provitamin D3. Dietary intake of vitamin D is very important when skin is exposed for short times to ultraviolet B light (UV-B) one of the three kind of invisible light rays together with UV-A and UV-C. This can be considered the usual situation in some latitude and in winter season, or the typical condition for older people and/or for people with vey white delicate skin. Actually, the recommended daily intake of dietary vitamin D is strictly correlated with age, ranging from 5 μg for infants, children, teen-agers and adults, including women during pregnancy and lactation, to 15 μg for people over 65 years.
Online: 29 February 2020 (11:17:52 CET)
The nervous system demands an adequate oxygen and metabolite exchange, making pericytes (PCs), the only vasoactive cells on the capillaries, essential to neural function. Loss of PCs is a hallmark of multiple diseases, including diabetes, Alzheimer’s, amyotrophic lateral sclerosis (ALS) and Parkinson’s. Platelet-Derived Growth Factor Receptors (PDGFRs) have been shown to be critical to the PC function and survival. However, how PDGFR-mediated PC activity affects vascular homeostasis is not fully understood. Here, we tested the hypothesis that imatinib, a chemotherapeutic agent and a potent PDGFR inhibitor, alters the PC distribution and thus induces vascular atrophy. We performed a morphometric analysis of the vascular elements in sham control and imatinib-treated NG2-DsRed mice. Vascular morphology and the integrity of the blood-retina barrier (BRB) were evaluated using blood albumin labeling. We found that imatinib decreased the number of PCs and blood vessel (BV) coverage in all retinal vascular layers, this was accompanied by a shrinkage of BV diameters. Surprisingly, the total length of capillaries was not altered, suggesting a preferential effect of imatinib on PCs. Furthermore, the blood-retina barrier disruption was not evident. In conclusion, our data suggest that imatinib could help in treating neurovascular diseases and serve as a model for PC loss, without BRB disruption.
Thu, 27 February 2020
REVIEW | doi:10.20944/preprints202002.0397.v1
Subject: Life Sciences, Other Keywords: Sugarcane, impacts, ecosystem services, human well-being, agro-systems, sustainability
Online: 27 February 2020 (10:56:50 CET)
Since the 1950s sugarcane production has grown rapidly from less than 0.5 billion tonnes in the late 50s to reach over 1.9 billion tonnes in 2012 on about 27 million hectares of agricultural land. This expansion has been boosted by the high demand for bioethanol promoted as a sustainable bioenergy source which accounted in 2010 for the biggest share of the global biofuel market. Despite its benefits, the scientific debate on sugar is growing especially that counterarguments are so many, including negative impacts on different interacting ecosystems and human well-being, e.g. bigger stress on land and water resources, environmental externalities on air, a harmful impact on the biodiversity and endemic species, negative environmental externalities, health, and socio-economic aspects. This paper provides a narrative systematic review (SR) of the impacts of sugarcane production on these different ecosystems employing the ecosystem services framework for its acceptance by policy-makers. The references included for the SR were 163 and results showed that the majority of the studies are from Brazil, Australia, South Africa and the USA (≈ 75% of the literature), most of them were from peer-reviewed journals (85%), and most of the case studies adopted a quantitative research approach (93%). The literature assessed showed that sugarcane, like all agro-systems, depends on the practices and techniques to transform negative impacts into positive externalities on ecosystems and human well-being. However, the literature studied failed to include the inter-linkage in sugarcane production impacts’ and therefore to evaluate the related ecosystem services with respect to the Millennium Ecosystem Assessment (MA) framework to account for existing trade-offs. Therefore, the findings are addressed to the scientific community and decision-maker for an intensification of interdisciplinary and integrated research based on the MA framework to cover all ecosystem services, for sustainable development of the sugarcane sector.
Tue, 25 February 2020
ARTICLE | doi:10.20944/preprints202002.0365.v1
Subject: Life Sciences, Other Keywords: corona virus; reported and unreported cases; isolation; quarantine; public closings; epidemic mathematical model
Online: 25 February 2020 (07:38:24 CET)
We model the COVID-19 coronavirus epidemic in China. We use early reported case data to predict the cumulative number of reported cases to a final size. The key features of our model are the timing of implementation of major public policies restricting social movement, the identification and isolation of unreported cases, and the impact of asymptomatic infectious cases.
HYPOTHESIS | doi:10.20944/preprints202002.0363.v1
Subject: Life Sciences, Other Keywords: amphimixis; apomixis; gynogenesis; hybridogenesis; parthenogenesis
Online: 25 February 2020 (06:40:06 CET)
The unusual occurrence and developmental diversity of asexual eukaryotes still remain a puzzle. Despite asexual organisms have a theorized two-fold reproductive advantage over sexuals, asexual lineages are rare among multicellular eukaryotes. Justification of such disparity relies on the consequences of a lack of meiosis, which restricts genotype diversity and adaptation to novel conditions while accelerating the genetic degeneration that drives asexual lineages to an early demise. However, evidence indicates asexuals use different strategies to limit negative consequences of ameiosis, and age estimates show some asexual vertebrates and plants are much older than expected. If rapid extinction is not a factor influencing asexuals lifespan, then why asexuals are not more frequent? Here we review traditional ideas and new data and provide a novel unified evolutionary frame to understand the intriguing nature, developmental diversity and maintenance of asexual lineages. As a rule, de novo formation of a functioning asexual genome requires a unique assemblage combining particular sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and affect discrete components of sexuality to produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, i.e. a non-recombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.
Wed, 19 February 2020
ARTICLE | doi:10.20944/preprints202002.0272.v1
Subject: Life Sciences, Other Keywords: Bread wheat; terminal drought; GWAS; grain yield; kernel abortion
Online: 19 February 2020 (10:48:02 CET)
Bread wheat (Triticum aestivum L.) is one of the most important cereal crops for food security. Of all the stresses that curtail wheat productivity, drought has the most detrimental effects. Especially terminal drought stress i.e. at the time of flowering imposes a big challenge to sustain grain production. In the current study, 339 pre-breeding lines derived from three-way crosses of exotics x elite lines were evaluated in the irrigated and drought stress environments at Obregon, Mexico for the year 2016 and 2018. Drought significantly reduced yield (Y), spike length (SL), number of grains per spikes (NGS) and thousand kernel weight (TKW) by 46.4, 19.2, 23.5 and 25.9%, respectively in comparison to irrigated conditions. Kernel abortion (KA), highly correlated with Y, increased significantly (11.6%) under drought stress environment. Population structure analysis in this panel revealed three sub-populations and a genome wide linkage disequilibrium (LD) decay was at 2.5 cM. Single marker and haplotypes-based genome wide association study (GWAS) revealed significant associations on three chromosomes; 4A (HB10.7), 2D (HB6.10) and 3B (HB8.12) with Y, SL and TKW, respectively. Likewise, associations on chromosomes 6B (HB17.1) and 3A (HB7.11) were identified for NGS and on 3A (HB7.12) for KA. Five traits i.e. normalized difference vegetation index (NDVI), canopy temperature depression (CTD) days to heading (DTH), NGS, KA were associated at chromosome 3A both under irrigated and drought conditions however, different haplotypes were estimated. Twenty-six SNPs were part of 10 haplotype blocks associated with Y, SL, TKW, NGS and KA. In silico analysis of the associated SNPs/haplotypes showed hits with candidate genes known to confer abiotic stress resistance in model species and crops. Potential candidate genes include those coding for sulfite exporter TauE/SafE family in Arabidopsis thaliana, TBC domain containing protein in Oryza sativa subsp. Japonica and heat shock proteins in Aegilops tauschii subsp. tauschii were revealed. The SNPs linked to the promising genes identified in the study can be used for marker-assisted selection.
Mon, 17 February 2020
ARTICLE | doi:10.20944/preprints202002.0250.v1
Subject: Life Sciences, Other Keywords: microRNAs; exosomes; astrocytes; hippocampal neurons; dendritic complexity
Online: 17 February 2020 (15:53:24 CET)
In the last decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) which are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e. GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation and also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.
ARTICLE | doi:10.20944/preprints202002.0246.v1
Online: 17 February 2020 (15:21:39 CET)
Background and Objectives: The site types of Eucalyptus urophylla × Eucalyptus grandis clonal plantations in southern Yunnan were compared, aiming to provide basis for site selection and scientific plantations management. Materials and Methods: In this study, 80 standard plots were set up in the 6−9-year-old Eucalypts plantations in Pu'er City and Lincang City. Furthermore, the quantitative theory I model and canonical correlation analysis were used to analyze the relationship between dominant tree growth traits and site factors, and evaluate the growth potential of E. urophylla × E. grandis plantation. Results: The multiple correlation coefficient between 8 site factors (altitude, slope, slope level, soil thickness, slope direction, texture, soil bulk density, and litter thickness) and the quantitative growth of the dominant wood was 0.825 (P < 0.05). According to the correlation coefficient of the quantitative regression model, slope, altitude, and soil thickness were the main factors for the classification of E. urophylla × E. grandis plantations in southern Yunnan. In addition, E. urophylla × E. grandis plantations grew best downhill and mid uphill at relatively low altitude, where the soil layer was thick and composed of weathered red soil. Contrastingly, E. urophylla × E. grandis plantation growth was extremely poor in uphill sites at higher altitude, where the soil layer was thin and composed of semi-weathered purple soil. Furthermore, total N, and available B, Cu, and Zn content, as well as soil organic matter content in the soil had a great influence on the growth of E. urophylla × E. grandis. Conclusions: Nitrogen and phosphate fertilizer as well as trace elements such as B, Zn, and Cu can be properly applied in middle- and low-yield forests to promote the growth and development of E. urophylla × E. grandis plantations.
Sun, 16 February 2020
Subject: Life Sciences, Other Keywords: consciousness; cognition; life; equivalence relation; synchrony; compartmentalization; closure; connectivity
Online: 16 February 2020 (15:01:47 CET)
In an analogous manner as occurred during the development of a connected metabolism that at some point reached characteristics associated with what is called ‘life’ ―due mainly to a catalytic closure phenomenon when chemicals started to autocatalyze themselves forming a closed web of chemical reactions― it is here proposed that cognition and consciousness (or features associated with them) arose as a consequence of another type of closure within the nervous system, the brain especially. Proper brain function requires an efficient web of connections and once certain complexity is attained due to the number and coordinated activities of the brain cell networks, the emergent properties of cognition and consciousness take place. Seeking to identify main features of the nervous system organization for optimal function, it is here proposed that while catalytic closure yielded life, neuroglial closure produced cognition/consciousness.
ARTICLE | doi:10.20944/preprints202002.0221.v1
Online: 16 February 2020 (14:56:57 CET)
ACE2, the putative receptor for the novel coronavirus (2019-nCoV), played an important role in cell entry of 2019-nCoV. However, it is not yet clear what cell types within the human body express ACE2. Here, a systematic analysis was undertaken using published single cell datasets. In total, our study analyzed 229652 cells, from five different organs, derived from 88 donors. The top ACE2 expressing cells include proximal tubule cells in the kidney and enterocytes in the intestine. Other major ACE2 expressing cells in the kidney include podocytes, intercalated cells and endothelial cells. Our results offer a comprehensive atlas of ACE2 expression at the single cell level and unravel the enormous potential targets of 2019-nCoVinfection beyond the lung.
Sat, 15 February 2020
REVIEW | doi:10.20944/preprints202002.0203.v1
Subject: Life Sciences, Other Keywords: Alzheimer’s disease; biomarkers dynamics; interaction; time order
Online: 15 February 2020 (15:06:18 CET)
The Aβ cascade and alternations of biomarkers in neuro-inflammation, synaptic dysfunction and neuronal injury followed by Aβ have progressed. But the question is how to use the biomarkers. Here, we examine the evidence and pathogenic implications of protein interactions and the time order of alternation. After the deposition of Aβ, the change of tau, NfL and NG is the main alternation and connection to others. The neuro-inflammation, synaptic dysfunction and neuronal injury function is exhibited prior the structural and metabolic changes in the brain following Aβ deposition. The time order of such biomarkers compared to the tau protein is not clear. Despite the close relationship between biomarkers and plaque Aβ deposition, several factors favor one or the other. There is an interaction between the proteins that CSF SNAP-25, VILIP-1 and YKL-40 can predict the brain amyloid burden. The Aβ cascade hypothesis could be the pathway, but not all subjects are converted to AD, even with very high elevated Aβ. The interaction of biomarkers and the time order of change require further research to identify the right subjects and right molecular target for precision medicine therapies.
Thu, 13 February 2020
ARTICLE | doi:10.20944/preprints202002.0169.v1
Subject: Life Sciences, Other Keywords: bark stripping; wallabies; supplementary food; radiata pine plantations
Online: 13 February 2020 (12:35:44 CET)
Bark stripping by the Bennett’s wallaby (Macropus rufogriseus rufogriseus) from the lower stems of 3–6-year-old radiata pine (Pinus radiata) causes significant damage in Tasmanian plantations. The usual diet of this generalist herbivore is mainly grasses and broadleaved forbs. As the factors that attract wallabies to supplement its diet by eating the bark of plantation pine trees are currently not elucidated, the present study aimed to determine how the incidence and severity of bark damage in 12 Tasmanian radiata pine plantations was influenced by various inter-site factors such as the floristic composition of the surrounding forest and by various intra-site factors such as the height and circumference of individual trees, the number of branches in the first two whorls at the base of the tree, and their internode lengths. Site differences in the observed percentage of bark stripping were found to be related to ‘ease of access’ variables such as bare ground, bracken, and moss, ‘hindrance to access’ variables such as rock and woody debris, and the percentage of grass, the wallaby’s main food source, present in the five plots at each site. The difference between the mean minimum soil and air temperatures in spring, a driving force for carbohydrate production that occurs with tree growth in spring or early summer, was the only meteorological observation at the sites that was found to be statistically significant. Nevertheless, there was no direct evidence that it was the movement of sugars in the phloem tissue accompanying tree growth which provided wallabies with a supplementary food source.
Tue, 11 February 2020
REVIEW | doi:10.20944/preprints202002.0146.v1
Subject: Life Sciences, Other Keywords: data science; reuse; sequencing data; genomics; bioinformatics; databases; computational biology; open science
Online: 11 February 2020 (11:48:25 CET)
The 'big data revolution' has enabled novel types of analyses in the life sciences, facilitated by public sharing and reuse of datasets. Here, we review the prodigious potential of reusing publicly available datasets and the challenges, limitations and risks associated with it. Due to the prominence, abundance and wide distribution of sequencing results, we focus on the reuse of publicly available sequence datasets. Through selected examples of successful reuse of different data (genome, transcriptome, proteome, metabolome, phenotype and ecosystem), with their respective limitations and risks, we illustrate the enormous potential of the practice. A checklist to determine the reuse value and potential of particular dataset is also provided.
Thu, 6 February 2020
ARTICLE | doi:10.20944/preprints202002.0083.v1
Subject: Life Sciences, Other Keywords: Cardiorespiratory Fitness; Muscle Strength; Feeding Patterns; Life Style; Children
Online: 6 February 2020 (10:27:07 CET)
Background: The relationship between adherence to the Mediterranean Diet (MD) and both physical fitness (PF) and physical activity (PA) level has been analysed in several studies. The aim of this research was to describe, compare and analyse the level of PF and PA in schoolchildren aged 6-13 in the Region of Murcia, according to adherence to the MD. Methods: A descriptive and cross-sectional study was performed. A total of 370 schoolchildren (44.9% girls) aged 6-13 (8.7±1.8) from six primary schools in the Region of Murcia (Spain). Results: Only 25.9% of the schoolchildren had optimal adherence to the MD. Regarding the scores of the different PF tests in MD groups, only statistically significant differences were found for CRF (p=0.048) in boys. PA level, showed statistically significant differences in both boys (p=0.040) and girls (p=0.016). A positive relationship was found between the KIDMED index and CRF (ρ=.127), standing broad jump (ρ=.133) and PA level (ρ=.235). A higher probability of having a greater CRF (OR=1.17; CI95%=1.02–1.34) and PA level (OR=7.84; CI95%=2.84–21.60) was found in High MD group. Conclusion: These results suggest that an optimal adherence to the MD is associated with higher CRF and PA level in the selected schoolchildren.
Online: 6 February 2020 (04:02:21 CET)
Learning models of the cerebellum propose that the cerebellum implements an algorithm which makes iterative adjustments to synaptic transmission strength that collectively determine the response to input in learned patterns following training. We propose instead that pattern recognition and control of firing by output cells are separately handled functions which process independently variable data. This can account for the evidence without a machine learning algorithm. The model is a hybrid of physiological arguments and computational methods used to test and quantify the ideas. We argue inter alia that learning operates at the level of functional groups of Purkinje cells defined by their shared climbing fibre input; Golgi cells have several functions and regulation of parallel fibre activity by Golgi cells is not in the expected way; recoding of input to the cerebellum received in the granular layer converts the number of input variables (variables expressed in mossy fibre input to the system) into a much reduced number of functional variables expressed by internal signals traffic; circuits simultaneously execute separate but integrated functions of pattern memory and output coding; they are able to operate separately because the expression of data used in each varies independently of the other; output rates are not learned but controlled by recent relevant input signals in a window opened by pattern memory; the moment-to-moment probability that a Purkinje cell spikes is synchronised across a microzone; a principal function of functional organisation of Purkinje cells into microzones is to increase resolution of rate coded information received by the output cells of the circuit, and to do so in a very short integration window, so that circuit architecture can be explained partly as a device with this function.
Tue, 4 February 2020
HYPOTHESIS | doi:10.20944/preprints202002.0039.v1
Subject: Life Sciences, Other Keywords: LUCA; FUCA; horizontal biomolecule transfer; horizontal gene transfer
Online: 4 February 2020 (05:27:46 CET)
The central mechanism of biological evolution, variation-selection-inheritance (VSI), is one of the most universal mechanisms known. Much of our understanding of VSI, however, has been dominated by the Neo-Darwinian Modern Synthesis with a rather narrow understanding of what constitutes variation, selection, and inheritance. This unduly narrow understanding of VSI might have been a key cause behind our failure to adequately explain some critical puzzles in biological evolution, from the origin of the first cell to the origin of the eukaryotes, the puzzling biology of metabolism, apoptosis, aging, and cancer in metazoan.I broaden our understanding of VSI, in a spirit that is somewhat similar to several recent contributions and then extend this broadened view of VSI to its natural starting point: the origin of the First Universal Cell Ancestor (FUCA). I advance three principal arguments. First, survival comes before replication. Before the coming of reproducer and replicator, there must be survivors, to paraphrase Szathmary and Maynard Smith (1997). Second, natural selection, especially the non-Darwinian kind, can operate without replication or even metabolism, as long as different molecules, complexes, and vesicles have differential survival rate within a system. Third, merger and acquisition, via breaking-and-re-encapsulation, endocytosis, endosymbiosis, and processes similar to them, had been a far more powerful force of variation and selection in the pre-Darwinian period of evolution that led to LUCA and long before eukaryogenesis. Endosymbiosis therefore had been a far more foundational force than even Lynn Margulis and many of her supporters have appreciated. Our thesis thus goes beyond Woese’s emphasis of horizontal gene transfer (HGT) and actually subsumes HGT with Margulis’ emphasis of endosymbiosis. Combing these three new perspectives with other perspectives and evidence sheds important new light upon the origin of FUCA, the singular water-shedding moment in the evolution of life.
Fri, 31 January 2020
REVIEW | doi:10.20944/preprints202001.0378.v1
Subject: Life Sciences, Other Keywords: workflows; containers; cloud computing; Kubernetes; big data; reproducibility
Online: 31 January 2020 (05:15:01 CET)
Containers are gaining popularity in life science research as they provide a solution for encompassing dependencies of provisioned tools, simplify software installations for end users and offer a form of isolation between processes. Scientific workflows are ideal for chaining containers into data analysis pipelines to aid in creating reproducible analyses. In this manuscript we review a number of approaches to using containers as implemented in the workflow tools Nextflow, Galaxy, Pachyderm, Argo, Kubeflow, Luigi and SciPipe, when deployed in cloud environments. A particular focus is placed on the workflow tool’s interaction with the Kubernetes container orchestration framework.
Mon, 27 January 2020
Subject: Life Sciences, Other Keywords: obesity; mesenchymal stromal cells; cell cycle; senescence; differentiation
Online: 27 January 2020 (09:18:05 CET)
White adipose tissue (WAT) is distributed in several depots that have distinct metabolic and inflammatory functions. In our body there are subcutaneous (sWAT), visceral (vWAT) and bone marrow fat depots (BFAT). Obesity affects size, function and inflammatory state of WATs. This process can alter the stem cell niches present in these tissues and affect the functions of stem cells residing within. In particular, obesity may affect the activity of mesenchymal stromal cells (MSCs) present in WAT. MSCs are an heterogenous population containing stromal cells, progenitor cells, fibroblasts and stem cells that are able to differentiate in adipocytes, chondrocytes, osteocytes and other mesodermal derivatives. We performed a comparison of the effects of obesity on MSCs obtained from sWAT, vWAT and BFAT. Our study evidenced that obesity affected mainly the biological functions of MSCs obtained from bone marrow and vWAT with a decrease in proliferation rate, reduced percentage of cells in S phase and trigger of senescence. The onset of senescence was confirmed by expression of genes belonging to RB and P53 pathways. Our study evidenced that negative consequences of obesity on body physiology may be related also to impairment in the functions of stromal compartment present in the several adipose tissues. This finding provides new insights on the targets that should be considered for an effective treatment of obesity-related diseases.
ARTICLE | doi:10.20944/preprints202001.0320.v1
Subject: Life Sciences, Other Keywords: conjugated linolenic acid; Caco-2 cell; lipid peroxidation; apoptosis; pyroptosis
Online: 27 January 2020 (02:03:33 CET)
The probiotic bacterial strain Lactobacillus plantarum ZS2058 has been proved to manifest comprehensive functions, which were due to ability to synthesise conjugated fatty acids (CFAs). To investigate the specific functions of CFAs produced by this probiotic bacterium, α-linolenic acid was isomerized by Lactobacillus plantarum strain ZS2058, and two different conjugated α-linolenic acid (CLNA) isomers were successfully isolated. These isoforms, CLNA1 (c9, t11, c15-CLNA, purity 97.48%) and CLNA2 (c9, t11, t15-CLNA, purity 99.00%), both showed the ability to inhibit the growth of three types of colon cancer cells in a time- and concentration-dependent manner. In addition, the expression of MDA in Caco-2 cells was increased by CLNA1 or CLNA2, which indicated lipid peroxidation was related to the antiproliferation activity of CLNAs. Examination of the key protein of pyroptosis showed that CLNA1 induced the cleavage of caspase-1 and gasdermin-D, while CLNA2 induced the cleavage of caspase-4, 5 and gasdermin-D. The addition of relative inhibitors could alleviate the pyroptosis by CLNAs. CLNA1 and CLNA2 showed no effect on caspase-3, 7, 9 and PARP-1, which were key proteins associated with apoptosis. And no sub-diploid apoptotic peak appeared in the result of PI single staining test. In conclusion, CLNA1 activated caspase-1 and induced Caco-2 cell pyroptosis, whereas CLNA2 induced pyroptosis through the caspase-4/5-mediated pathway. The inhibition of Caco-2 cells by the two isomers was not related to apoptosis. This is the first report showing the ability of CLNAs to activate antioxidant defenses resulting in pyroptosis.
Sun, 26 January 2020
ARTICLE | doi:10.20944/preprints202001.0302.v1
Subject: Life Sciences, Other Keywords: fractional SEIR stochastic model; Caputo fractional order differential equations; measles; parameter estimation
Online: 26 January 2020 (03:38:06 CET)
In this paper, we compare the performance between systems of ordinary and (Caputo) fractional differential equations depicting the susceptible-exposed-infectious-recovered (SEIR) models of diseases. In order to understand the origins of both approaches as mean-field approximations of integer and fractional stochastic processes, we introduce the fractional differential equations as approximations of some type of fractional nonlinear birth--death processes. Then, we examine validity of the two approaches against empirical courses of epidemics; we fit both of them to case counts of three measles epidemics that occurred during the pre-vaccination era in three different locations. While FDEs appear more flexible in fitting empirical data, our ODEs offered better fits to two out of three data sets. Important differences in transient dynamics between these modeling approaches are discussed.
Sat, 25 January 2020
BRIEF REPORT | doi:10.20944/preprints202001.0292.v1
Subject: Life Sciences, Other Keywords: circadian rhythms; small molecules; luciferase reporters; period estimations
Online: 25 January 2020 (00:33:40 CET)
We present a summary of our protocol for employment of small-molecule circadian rhythm modulators. The abilities of compounds to affect oscillations have received significant attention. We outline assessments of circadian changes using indirubin-3’-oxime (IO), 5-iodo-indirubin-3’-oxime (5I-IO), and 5-sulfonic acid-indirubin-3’-oxime (5SA-IO), analyzing effects on Bmal1 and Per2 oscillations and oncogenic features.
Wed, 22 January 2020
ARTICLE | doi:10.20944/preprints202001.0259.v1
Online: 22 January 2020 (09:40:45 CET)
Background There is anecdotal evidence that ivermectin may decrease the frequency of seizures in Onchocerca volvulus-infected persons with epilepsy (PWE). Methods In October 2017, a 12-month clinical trial was initiated in rural Democratic Republic of Congo. PWE with onchocerciasis-associated epilepsy with ≥2 seizures/month were randomly allocated to receive over a one year period, ivermectin once or thrice (group 1), while other onchocerciasis-infected PWE (OIPWE) were randomized to ivermectin twice or thrice (group 2). All participants also received anti-epileptic drugs (AED). Study outcomes included seizure freedom during the last four months (primary endpoint), decrease in microfilarial density, and occurrence of adverse events. A multiple logistic regression model was used to evaluate the primary outcome. Results Of the 197 OIPWE enrolled, 100 were randomized to receive ivermectin thrice, 52 twice, and 45 once. In an intent-to-treat combined analysis of data from group 1 and 2, the probability to become seizure-free for OIPWE treated with ivermectin twice per year was significantly higher than in those treated once (OR: 5.087, 95% CI: 1.378-19.749; p=0.018) and individuals who received ivermectin twice had a 4.471 (95% CI: 0.944-6.769, p=0.075) times higher odds of seizure freedom than those received ivermectin once per year. Absence of microfilariae during the last 4 months was associated with a higher probability of seizure freedom (p=0.027). Conclusions Increasing the number of ivermectin treatments per year was found to suppress both microfilarial density and seizure frequency in OIPWE, suggesting that O. volvulus infection plays an etiological role in causing seizures. Registration: www.clinicaltrials.gov; NCT03852303
Sun, 5 January 2020
Online: 5 January 2020 (15:16:56 CET)
Photodynamic therapy has been applied endoscopically to treat early esophageal cancer. However, the long-term survival outcome of this treatment option is unknown in literature. Patients and Method: The patients of early esophageal cancer (clinical stage I) treated with photophrin based photodynamic therapy were analyzed for their long-term survival outcome and compared to those patients undergoing esophagectomy by a single surgeon for stage I disease. Results: There were 15 and 16 patients undergoing PDT and esophagectomy enrolled in the current study respectively. Complete response was achieved in 10 (66.7%) patients after PDT. After adjuvant chemoradiation (CCRT) complete response was achieved in 13 patients (86%). There is no mortality after PDT. Severe complication was detected in 3 patients including trachea-esophageal fistulae, esophageal stenosis and skin photosensitivity respectively. With a median follow-up duration of 110.2 months (+9.6 months) for the patients after PDT, there were 4 and 3 recurrence in the primary tumor site and regional lymph node respectively with 73.3% of successful local control rate of the primary tumor. There were 7 (46.7%) patients died during clinical follow-up of this cohort with 5 (33.3%) from disease progression of esophageal cancer and two from other diseases respectively. The five-year survival rate after PDT is 64.3%, whereas 70.9% of the patients after esophagectomy without significant difference of these two group of patients (P=0.72). Conclusion: Our preliminary results suggested that PDT might provide an equivalent long-term oncological outcome as compared to that done by esophagectomy for early esophageal cancer. A prospective randomized clinical trial comparing the results with esophagectomy and other endoscopic abrasive therapies is warrant in the future.
Thu, 2 January 2020
ARTICLE | doi:10.20944/preprints202001.0009.v1
Online: 2 January 2020 (04:33:47 CET)
The nervous system demands an adequate oxygen and metabolite exchange, making pericytes (PCs), the only vasoactive cells on the capillaries, essential to neural function. Loss of PCs is a hallmark of multiple diseases, including diabetes, Alzheimer’s, ALS and Parkinson’s. Platelet-Derived Growth Factor Receptors (PDGFRs) have been shown to be critical to the PC function and survival. However, how PDGFR-mediated PC activity affects vascular homeostasis is not fully understood. Here, we tested the hypothesis that Imatinib, a chemotherapeutic agent and a potent PDGFR inhibitor, alters the PC distribution and thus induces vascular atrophy. We performed a morphometric analysis of the vascular elements in sham control and Imatinib-treated NG2-DsRed mice. Vascular morphology and the integrity of the blood-retina barrier (BRB) were evaluated using blood albumin labeling. We found that Imatinib decreased the number of PCs and blood vessel (BV) coverage in all retinal vascular layers, this was accompanied by a shrinkage of BV diameters. Surprisingly, the total length of capillaries was not altered, suggesting a preferential effect of Imatinib on PCs. Furthermore, the blood-retina barrier disruption was not evident. In conclusion, our data suggests that Imatinib could help in treating neurovascular diseases and serve as a model for pericyte loss, without BRB disruption.
Wed, 25 December 2019
REVIEW | doi:10.20944/preprints201912.0332.v1
Online: 25 December 2019 (03:24:53 CET)
Natural products (NPs) have been the centre of attention of the scientific community in the last decencies and the interest around them continues to grow incessantly. As a consequence, in the last 20 years, there was a rapid multiplication of various databases and collections as generalistic or thematic resources for NP information. In this review, we establish a complete overview of these resources, and the numbers are overwhelming: over 120 different NP databases and collections were published and re-used since 2000. 98 of them are still somehow accessible and only 50 are open access. The latter include not only databases but also big collections of NPs published as supplementary material in scientific publications and collections that were backed up in the ZINC database for commercially-available compounds. Some databases, even published relatively recently are already not accessible anymore, which leads to a dramatic loss of data on NPs. The data sources are presented in this manuscript, together with the comparison of the content of open ones. With this review, we also compiled the open-access natural compounds in one single dataset a COlleCtion of Open NatUral producTs (COCONUT), which is available on Zenodo and contains structures and sparse annotations for over 400000 non-redundant NPs, which makes it the biggest open collection of NPs available to this date.
Tue, 24 December 2019
Subject: Life Sciences, Other Keywords: neural differentiation; regulatory motif; feedback regulation; signaling pathway; mathematical models
Online: 24 December 2019 (11:20:25 CET)
Computational simulation using mathematical models is a useful method for understanding the complex behavior of a living system. The majority of studies using mathematical models to reveal biological mechanisms uses one of the two main approaches: the bottom-up or the top-down approach. When we aim to analyze a large-scale network, such as a comprehensive knowledge-integrated model of a target phenomenon, for example a whole-cell model, the variation of analyses is limited to particular kind of analysis because of the size and complexity of the model. To analyze a large-scale regulatory network of neural differentiation, we developed a hybrid method that combines both approaches. To construct a mathematical model, we extracted network motifs, subgraph structures that recur more often in a metabolic network or gene regulatory network than in a random network, from a large-scale regulatory network, detected regulatory motifs among them, and combined these motifs. We confirmed that the model reproduced the known dynamics of HES1 and ASCL1 before and after differentiation, including oscillation and equilibrium of their concentrations. The model also reproduced the effects of overexpression and knockdown of the Id2 gene. Our model suggests that the characteristic change in HES1 and ASCL1 expression in the large-scale regulatory network is controlled by a combination of four feedback loops, including a large loop which has not been focused on. The model extracted by our hybrid method has the potential to reveal the critical mechanisms of neural differentiation. The hybrid method is applicable to other biological events.
Wed, 18 December 2019
CONCEPT PAPER | doi:10.20944/preprints201912.0236.v1
Subject: Life Sciences, Other Keywords: microlearning; culturally-responsive teaching; inclusion; equity; life science education
Online: 18 December 2019 (04:27:11 CET)
Some of the key features of inclusive and equitable teaching approaches encourage prompt feedback, student cooperation in communities of learning, active learning, and promotes diverse ways of knowing in the classroom. In my article, I present step-bystep tips to help instructors create guided microlearning inquiry questions within an inclusive and equitable general biology classroom setting. Microlearning is a special approach that helps students complete a specific task linked to a specific learning objective that would be completed in a short time window around five minutes. The step-by-step tips presented in my article helps instructors to develop questions aligned to specific learning objective to help clarify unclear or confusing topics in general biology using the Kahoot e-Learning platform. This guided microlearning inquiry toolkit provides a blueprint for helping instructors to infuse student-centered approaches to help clarify difficult concepts in general biology and further develop avenues refine students’ critical thinking and experimental design in biology research.
Thu, 12 December 2019
Subject: Life Sciences, Other Keywords: gene prioritization; osteosarcoma; communality analysis; pathogenesis; early recognition
Online: 12 December 2019 (05:45:18 CET)
Osteosarcoma is the most common subtype of primary bone cancers, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein-protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events such as MMP2 and MMP9 and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we could identify well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.
Tue, 10 December 2019
Subject: Life Sciences, Other Keywords: Indian pangolin; dietary; habitats; foraging intensity; faecal
Online: 10 December 2019 (03:06:05 CET)