ARTICLE | doi:10.20944/preprints202105.0553.v1
Subject: Biology, Anatomy & Morphology Keywords: mushroom; organic-debris; fruiting bodies; diversity; frequency
Online: 24 May 2021 (10:22:51 CEST)
A The present investigation was undertaken in foothill regions of Uttarakhand from July-2016 up to December-2018. A total of thirty four different sites ranging from the roadside areas, grasslands to forests were studied and Mushroom fruiting bodies were collected. A total of One Hundred sixty six fruiting counts were obtained and 68 mushroom genera belonging to 15 orders and 43 families were identified. During collection visits mushroom were apparent from organic debris of diversified habitats ranging from humid soil; grassland; leaf litter; living tree trunk; dead wood log of forest zone. Maximum fruiting bodies (75%) were obtained between July to September and minimum i.e. 6% between November – February. Among the collected mushroom Stereum rugosum, Crepidotus variabilis, Laccaria laccata, Schizophyllum commune, Ganoderma applantum, Cantharellus cibarius were more prevalent. Out of all collected mushroom sample the frequency of Mushroom belonging to order Agaricales was 45.18% followed by Polyporales i.e., 27.7%. The collected mushroom were cultured on PDA medium and their mycelial forms were preserved for further studies.
Subject: Life Sciences, Virology Keywords: Ebola virus; filovirus; inclusion bodies; CAD; pyrimidine synthesis
Online: 21 April 2020 (09:48:15 CEST)
Ebola virus (EBOV) is a zoonotic pathogen causing severe hemorrhagic fevers in humans and non-human primates with high case fatality rates. In recent years, the number and extent of outbreaks has increased, highlighting the importance of better understanding the molecular aspects of EBOV infection and host cell interactions to control this virus more efficiently. Many viruses, including EBOV, have been shown to recruit host proteins for different viral processes. Based on a genome-wide siRNA screen, we recently identified the cellular host factor carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) to be involved in EBOV RNA synthesis. However, mechanistic details of how this host factor plays a role in the EBOV life cycle remain elusive. In this study, we analyzed the functional and molecular interactions between EBOV and CAD. To this end, we used siRNA knockdowns in combination with various reverse-genetics based lifecycle-modelling systems and additionally performed co-immunoprecipitation and co immunofluorescence assays to investigate the influence of CAD on individual aspects of the EBOV life cycle and to characterize the interactions of CAD with viral proteins. Following this approach, we could demonstrate that CAD directly interacts with the EBOV nucleoprotein NP, and that NP is sufficient to recruit CAD into inclusion bodies dependent on the GLN-domain of CAD. Further, siRNA knockdown experiments indicated that CAD is important for both viral genome replication and transcription, while substrate rescue experiments showed that the function of CAD in pyrimidine synthesis is indeed required for those processes. Together this suggests that NP recruits CAD into inclusion bodies via its GLN domain in order to provide pyrimidines for EBOV genome replication and transcription. These results define a novel mechanism by which EBOV hijacks host cell pathways in order to facilitate genome replication and transcription, and provide further basis for the development of host directed broad spectrum antivirals.
REVIEW | doi:10.20944/preprints202009.0133.v1
Subject: Life Sciences, Other Keywords: Cognition; nutrition; metabolism; neurodegeneration; ketone bodies; glycaemia; nutrition therapy
Online: 5 September 2020 (08:29:52 CEST)
Although diet interventions are mostly related to metabolic disorders, nowadays they are used in wide variety of pathologies. From diabetes and obesity to cardiovascular diseases, through cancer or neurological disorders and stroke, nutritional recommendations applied to almost all diseases. Among those disorders, metabolic disturbances and brain function and/or diseases have recently been shown to be linked. Indeed, numerous neurological functions are often associated with perturbations of whole-body energy homeostasis. In this regard, specific diets are used in various neurological conditions such as epilepsy, stroke, or seizure recovery. In addition, Alzheimer’s disease or Autism Spectrum Disorders are also considered as putatively improved by diet intervention. Glycemic index diets are a novel developed indicator expected to anticipate the changes in blood glucose induced by specific foods, and how they can affect various physiological function. Several results provide indications of efficiency of low glycemic index diets in weight management, insulin sensitivity, but also cognitive function, epilepsy treatment, stroke, or neurodegenerative diseases. Overall, studies involving glycemic index could provide new insight in the relationship between energy homeostasis regulation and brain function or related disorders. Therefore, in this review we will summarize main evidences on glycemic index involvement in brain mechanisms of energy homeostasis regulation.
ARTICLE | doi:10.20944/preprints202105.0274.v1
Subject: Social Sciences, Sociology Keywords: Presidential elections; political parties; survey; democracy; supervisory bodies; Peruvian citizenship
Online: 12 May 2021 (15:58:48 CEST)
Background and objectives: In the current context, the 2021 presidential elections in Peru distance from the social objective, not being objectively represented, that is why we analyze their validity, we determine the distances between the parties if they are extreme, the correspondences with the departments and their prospects, in the surveys we propose which departments influence the results. Methods: We use a mixed methodology, qualitative analysis, it will be multidimensional with the support of statistical methods and programs such as R Studio, worddj, Gephi, and Iramuteq. The quantitative analysis will be through factor analysis, correspondence and discriminant analysis to the data of the election Results and conclusions: The textual analysis mentions that there are dimensions such as the social issue, the results of the surveys and democracy that are far apart, regarding the electoral issue. This inculcates to work both on the part of the organisms that carry out these processes, as well as the initiative of the candidates, and the media. Regarding the quantitative analysis, it is detailed that the representative parties must be greater than 4.0 million voters, to make representative parties at the national level. The classification regarding the percentage of votes is given in three groups, highlighting the independence of the Peru Libre political party in these . In the correspondence analysis we can detail that both Fuerza Popular and Peru Libre are extremist parties. The vast majority of Peruvian citizens have an ideological tendency, intermediate between both parties. The prospective projections with a cross section give a victory to the Peru Libre party. In the discriminant analysis, the sample for the surveys focuses on 7 departments that does not include the Peruvian capital.
REVIEW | doi:10.20944/preprints201911.0076.v3
Subject: Life Sciences, Genetics Keywords: phase separation; nuclear bodies; self-assembly; genome organization; gene expression
Online: 11 December 2019 (11:17:34 CET)
The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.
ARTICLE | doi:10.20944/preprints201805.0183.v1
Subject: Arts & Humanities, General Humanities Keywords: death; bodies; human rights; burial; ethics; tourism; heritage; culture; memory
Online: 14 May 2018 (05:32:40 CEST)
In The Work of the Dead: A Cultural History of Mortal Remains, Thomas Laqueur argues that the work of the dead is carried out through the living and through those who remember, honour, and mourn the dead. Further, he maintains that the brutal or careless disposal of the corpse “is an attack of extreme violence”. To treat the dead body as if it does not matter or as if it were ordinary organic matter would be to deny its humanity. From Laqueur’s point of view it is inferred that the dead are believed to have rights and dignities that are upheld through rituals, practices, and beliefs of the living. Drawing on dark tourism scholarship and cultural memory theory, this paper examines the display of human bones at Sedlec Ossuary, Czech Republic and the tourist culture that has built up around the site. Primarily, my writing calls into question the commoditization of burial places as a conceivable violation of the human rights of the dead. My research is driven by a number of questions: What is it that draws tourists to burial grounds and how do heritage sites negotiate visitor experiences? What are the ethical boundaries when a final resting place with bodies on display is also marketed as a tourist site? Do the dead have human rights and how are the living responsible for preserving those rights?
HYPOTHESIS | doi:10.20944/preprints202104.0606.v2
Subject: Life Sciences, Biophysics Keywords: Parkinson’s disease; alpha-synuclein; Lewy bodies; phase transition; thermodynamics; and mitochondria
Online: 10 January 2022 (12:23:19 CET)
I wish to suggest a physiological function for alpha-synuclein (a-syn) that has the potential to explain its role in pathology. Intraneuronal proteinaceous Lewy Bodies (LBs), the pathological hallmark of Parkinson’s disease and other synucleinopathies, consist majorly of a-syn. Ample evidence suggests that LBs are not the result of simple amyloidosis of cytosolic a-syn. Benign soluble unstructured a-syn gets converted into toxic species which preferentially accumulates in LBs. But how these aberrant a-syn molecules are produced in the cytosol, is still not clear. The present hypothesis is an effort to relate a metabolic reaction specific to neuronal function, that is, phase transition, with the pathobiology of a-syn. During high frequency stimulation, which entails rapid phase transition reactions at the presynaptic compartment, aberrant interaction of a-syn with the membrane occasionally generates toxic a-syn molecules. My conjecture is that the physiological function of a-syn is to modulate membrane fluidity by a process wherein it goes through a conformation cycle driven by a flux of energy from mitochondria. It is the range of toxic a-syn produced during aberrant phase transition reaction that is responsible for pathology, not the normal a-syn that reenters the conformation cycle, thereby, resolving the paradox of the Janus-face of a-syn.
REVIEW | doi:10.20944/preprints202212.0497.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: cognitive impairment; dementia; oral pathogens; periodontitis; inflammatory biomarkers; anti-bodies; systematic review
Online: 27 December 2022 (01:41:02 CET)
Introduction: Periodontitis is a severe oral infection that can contribute to systemic inflammation. A large body of evidence suggests a role for systemic inflammation in the initiation of neurodegenerative disease. This systematic review synthesized data from observational studies to investigate the association between periodontitis and neuroinflammation in adults. Methods and materials: A systematic literature search of PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) was performed for studies published from the date of inception up to September 2021. Search terms for the exposure “oral disease” and outcome “dementia”, “neuroinflammation” and “cognitive decline” were used. Study selection and data extraction were independently undertaken by two reviewers. The final eligible articles were included only if the exposure is periodontitis and the outcome is cognitive impairment or dementia or a topic related to this condition, and if the study was conducted in an adult population. The quality and risk of bias were assessed by Newcastle Ottawa Scale (NOS). Qualitative synthesis was used to narratively synthesize the results. Six cohort studies, three cross-sectional studies, and two case-control studies met the inclusion criteria. These eleven studies were only narratively synthesized. Meta-analysis was not performed due to the methodological heterogeneity of the studies. Results: All the included studies show evidence of an association between periodontitis and cognitive im-pairment or dementia and Alzheimer’s disease pathology. Conclusion: Nonetheless, the mechanisms responsible for the association between periodontitis and dementia are still unclear.
ARTICLE | doi:10.20944/preprints201908.0225.v1
Subject: Earth Sciences, Geoinformatics Keywords: water bodies; satellite images; vector data; SVM; positive and negative buffering; polygons
Online: 21 August 2019 (10:30:16 CEST)
The technique of obtaining information or data about any feature or object from afar, called in technical parlance as remote sensing, has proven extremely useful in diverse fields. In the ecological sphere, especially, remote sensing has enabled collection of data or information about large swaths of areas or landscapes. Even then, in remote sensing the task of identifying and monitoring of different water reservoirs has proved a tough one. This is mainly because getting correct appraisals about the spread and boundaries of the area under study and the contours of any water surfaces lodged therein becomes a factor of utmost importance. Identification of water reservoirs is rendered even tougher because of presence of cloud in satellite images, which becomes the largest source of error in identification of water surfaces. To overcome this glitch, the method of the shape matching approach for analysis of cloudy images in reference to cloud-free images of water surfaces with the help of vector data processing, is recommended. It includes the database of water bodies in vector format, which is a complex polygon structure. This analysis highlights three steps: First, the creation of vector database for the analysis; second, simplification of multi-scale vector polygon features; and third, the matching of reference and target water bodies database within defined distance tolerance. This feature matching approach provides matching of one to many and many to many features. It also gives the corrected images that are free of clouds.
ARTICLE | doi:10.20944/preprints202201.0080.v1
Subject: Life Sciences, Virology Keywords: Hantavirus; N protein; oligomerization; actin; P-Bodies; vimentin; Number&Brightness; Puumalavirus; macromolecular assemblies
Online: 6 January 2022 (11:45:52 CET)
Hantaviruses are enveloped viruses that possess a tri-segmented, negative-sense RNA genome. The viral S-segment encodes the multifunctional nucleocapsid protein (N), which is involved in genome packaging, intracellular protein transport, immunoregulation and several other crucial processes during hantavirus infection. In this study we have generated fluorescently tagged N protein constructs derived from Puumalavirus, the dominant hantavirus species in Central, Northern and Eastern Europe. We have comprehensively characterized this protein in the rodent cell line CHO-K1, monitoring the dynamics of N protein complex formation and investigating co-localization with host proteins as well as the viral glycoproteins Gc and Gn. We found a significant spatial correlation of N with vimentin, actin and P-bodies, but not with microtubules. N constructs also co-localized with Gn and Gc, albeit not as strong as the glycoproteins associated with each other. Moreover, we as-sessed oligomerization of N constructs, observing efficient and concentration-dependent multi-merization, with complexes comprising more than 10 individual proteins.
ARTICLE | doi:10.20944/preprints201804.0024.v1
Subject: Earth Sciences, Environmental Sciences Keywords: pollutant transport modelling; metals transport modelling; free surface water bodies; toxics-reaction equation
Online: 2 April 2018 (11:27:40 CEST)
This paper describes the development of a two-dimensional water quality model that solves hydrodynamic equations tied to transport equations with reactions mechanisms inherent in the processes. This enable us to perform an accurate assessment of the pollution in a coastal ecosystem. The model was developed with data drawn from the ecosystem found in Mexico's southeast state of Tabasco. The coastal ecosystem consists of the interaction of El Yucateco lagoon with the Chicozapote and Tonalá rivers, that connect the lagoon with the Gulf of Mexico. We present the results of pollutants transport simulation in the coastal ecosystem, focusing on toxic parameters for two hydrodynamic scenarios: wet and dry seasons. As it of interest in the zone, we study the transport of four metals: Cadmium, Chromium, Nickel and Lead. In order to address our objectives we solved numerically a self-posed mathematical problem,which is based on the measured data. The performed simulations show to characterise metal transport within the acceptable range of accuracy and in accordance with the measured data. The performed simulations show to characterise metals transport with an acceptable accuracy, agreeing well with measured data in total concentrations in four control points along the water body. Although for the accurate implementation of the hydrodynamic-based water quality model herein presented, boundary (geometry, tides, wind, etc.) and initial (concentrations measurements) conditions are required, it poses as an excellent option when the distribution of solutes with high accuracy is required, easing environmental, economic and social management of coastal ecosystems.
ARTICLE | doi:10.20944/preprints201810.0167.v1
Subject: Chemistry, Applied Chemistry Keywords: phytosterols; mesocarp; oilseed; maturity; pod-blast; α-tocopherol; oil bodies; campesterol; stigmasterol; β-sitosterol
Online: 9 October 2018 (04:02:35 CEST)
The seeds of cultivated peanut, Arachis hypogaea, are an agronomically important crop produced for human nutrition, oilseed and feed stock. Peanut seed is the single most expensive variable input cost and thus producers require seed with excellence performance in terms of germination efficiency. During the maturation process, triglycerides are stored in oil bodies as an energy resource during germination and seedling development. The stability of oil body membranes is essential for nutrient mobilization during germination. This study focused on evaluating the phytosterol composition in seed components including the kernel, embryo (heart), and seed coat or skin. Samples of different maturity classes were analyzed for macronutrient and phytosterol content. The three most abundant phytosterols, β-sitosterol, campesterol, and stigmasterol, comprised 82.29%, 86.39%, and 94.25% of seed hearts, kernels, and seed coats, respectively. Stigmasterol concentration was highest in the seed kernel providing an excellent source of this sterol known to have beneficial effects on human health. Peanut hearts contained the highest concentration of sterols by mass potentially providing protection and resources for the developing seedling. The amount of α-tocopherol increases in peanut hearts during the maturation process providing protection from temperature stress and stability required for seedling vigor. These results suggest that phytosterols may play a significant role in the performance of seeds and provides a possible explanation for the poor germination efficiency of immature seeds.
ARTICLE | doi:10.20944/preprints201711.0075.v1
Subject: Earth Sciences, Environmental Sciences Keywords: water quality; eutrophication; tropic state index; Landsat-8, RapidEye, tropical inland water bodies, Brazil
Online: 13 November 2017 (03:33:35 CET)
We aimed at analyzing Chlorophyll-a and CDOM dynamics from field measurements and at assessing the potential of multispectral satellite data for retrieving water-quality parameters in three small surface reservoirs in the Brazilian semiarid region. More specifically, this work comprises i) analysis of Chl-a and trophic dynamics; ii) characterization of CDOM; iii) estimation of Chl-a and CDOM from OLI/Landsat-8 and RapidEye imagery. The monitoring lasted 20 months within a multi-year drought, which contributed to water-quality deterioration. Chl-a and trophic state analysis showed a highly eutrophic status for the perennial reservoir during the entire study period, while the non-perennial reservoirs ranged from oligotrophic to eutrophic, with changes associated with the first events of the rainy season. CDOM characterization suggests that the perennial reservoir is mostly influenced by autochthonous sources, while allochthonous sources dominate the non-perennial ones. Spectral-group classification assigned the perennial as CDOM-moderate and highly eutrophic reservoir, whereas the non-perennial ones were assigned as CDOM-rich and oligotrophic-dystrophic reservoirs. The remote sensing initiative was partially successful: the Chl-a was best modelled using RapidEye for the perennial; whereas CDOM performed best with Landsat-8 for non-perennial reservoirs. This investigation showed high potential for retrieving water quality parameters in dry areas with small reservoirs.
ARTICLE | doi:10.20944/preprints202301.0238.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: induced pluripotent stem cells; embryoid bodies; light-sheet microscopy; multicolor fluorescence in situ hybridization; chromosomes
Online: 13 January 2023 (07:10:46 CET)
Embryoid bodies (EBs) are multicellular three-dimensional (3D) aggregates generated from induced pluripotent stem cells (iPSCs) in suspension and serve as useful biological sources for many downstream applications. Imaging of live EBs has been hampered mainly due to the inherent limitations of the imaging techniques applied to date. This study aimed to image human iPSC (hiPSC) derived EBs to obtain their 3D volume, determining size, morphology, and cell viability from day 7 to 14 using Light Sheet Fluorescence Microscopy (LSFM). Furthermore, chromosomal stability was assessed using Multicolor fluorescence in situ hybridization (M-FISH) from day 8 to 14. EB volume increased from day 7 to 13 which, decreased at day 14. From day 7 to 11, the EBs mainly appeared spherical and morphed into an ellipsoidal shape by day 13. All EBs showed varied external morphologies and larger cavities at day 14. The EB karyotype was diploid 46XY at day 8 and exhibited a low level of aneuploidy from day 10 to 14. This study shows that an increase in cell death affects the morphology and chromosomal stability in EBs derived from hiPSC. We demonstrate that the combination of LSFM and M-FISH helps characterize EBs that will assist future stem cell therapies.
ARTICLE | doi:10.20944/preprints202010.0367.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Human Activity Recognition; Smart Activity Sensors; Optimal Feature Selection; Colliding Bodies Optimization; Recurrent Neural Network
Online: 19 October 2020 (10:44:36 CEST)
— In a smart healthcare system," Human Activity Recognition (HAR)" is considered as an efficient approach in pervasive computing from activity sensor readings. The "Ambient Assisted Living (AAL)" in the home or community helps the people to provide independent care and enhanced living quality. However, many AAL models are restricted to multiple factors that include both the computational cost and system complexity. Moreover, the HAR concept has more relevance because of its applications, such as content-based video search, sports play analysis, crowd behavior prediction systems, patient monitoring systems, and surveillance systems. This paper attempts to implement the HAR system using a popular deep learning algorithm, namely "Recurrent Neural Network (RNN)" with the activity data collected from smart activity sensors over time, and it is publicly available in the "UC Irvine Machine Learning Repository (UCI)". The proposed model involves three processes: (1) data collection, (b) optimal feature learning, and (c) activity recognition. The data gathered from the benchmark repository was initially subjected to optimal feature selection that helped to select the most significant features. The proposed optimal feature selection method is based on a new meta-heuristic algorithm called "Colliding Bodies Optimization (CBO)". An objective function derived from the recognition accuracy has been used for accomplishing the optimal feature selection. The proposed model on the concerned benchmark dataset outperformed the conventional models with enhanced performance.
REVIEW | doi:10.20944/preprints202202.0022.v1
Subject: Life Sciences, Immunology Keywords: exosomes; T lymphocytes; immune synapse; secretory granules; multivesicular bodies; cytotoxic activity; cell death; CAR T lymphocytes
Online: 1 February 2022 (21:33:57 CET)
Extracellular vesicles (EV) are a very heterogeneous group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular communication, both locally and systemically, since they induce signals and transfer their contents (proteins, lipids, RNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. How-ever, cell surface receptor-induced EV release is limited to cells from the immune system, includ-ing T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptor for antigen and several bioactive molecules, including proapoptotic proteins. These EV are thus specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy. In this review we discuss the generation of EV by T lymphocytes and some potential therapeutic approaches of these EV.
ARTICLE | doi:10.20944/preprints202107.0025.v1
Subject: Life Sciences, Biochemistry Keywords: Orchid; Protocorm-like bodies; p-Chlorophenoxyisobutyric acid; PCIB; 3-Hydroxy-5-methyl isoxazole; HMI; light emitting diodes
Online: 1 July 2021 (12:28:44 CEST)
Dendrobium okinawense is an endangered epiphytic orchid, and there has been no scientific report so far on its propagation. Protocorm is mass of cell, and protocorm-like bodies (PLBs) look alike protocorm produced by vegetative explants in vitro. Regeneration of PLBs is the most efficient technique for the orchids micro-propagation. We used different light emitting diodes (LEDs) for the efficient PLB organogenesis of D. okinawense. PLBs regenartion under green and red LED surpassed respectively 81.1% and 71.6% in numbers, and respectively 80.8% and 57.8% in fresh weight over white fluorescent light. We manipulated the culture media by different concentrations of PCIB and HMI. PLBs organogenesis promoted by low concentration, it increased respectively 35.9% and 19.3% over control by 0.01 mg/L PCIB and 0.01 ml/L HMI in numbers. Green LED and PCIB independently produced mostly similar numbers of new PLBs. Interestingly, culture media with 0.01 mg/L of PCIB further increased 8.5% of the numbers of PLBs under green LED, whereas the culture media with 0.01 mg/L HMI reduced the number of PLBs under green LED. PLBs culture under green LED with very low concentrations of PCIB manipulated culture media can significantly increase their organogenesis of D. okinawense.
REVIEW | doi:10.20944/preprints202102.0277.v1
Subject: Life Sciences, Biochemistry Keywords: energy metabolism; oligodendrocyte; oligodendrocyte progenitor cell; myelin; remyelination; multiple sclerosis; glucose; ketone bodies; lactate; N-acetyl aspartate; demyelination
Online: 11 February 2021 (10:57:28 CET)
Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). This suggests that dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.
REVIEW | doi:10.20944/preprints201901.0081.v1
Subject: Life Sciences, Molecular Biology Keywords: gene regulation; translation; mRNA; IRES; ITAF; hnRNP; chaperone; stress; nucleocytoplasmic translocation; ribosome; lncRNA; translation initiation factor; P-bodies
Online: 9 January 2019 (08:49:45 CET)
The cellular stress response corresponds to the molecular changes that cell undergoes in response to various environmental stimuli. It induces drastic changes in the regulation of gene expression, at transcriptional and post-transcriptional levels. Actually, translation is strongly affected with a blockade of the classical cap-dependent mechanism, whereas alternative mechanisms are activated to support translation of specific mRNAs. One of the major mechanisms involved in stress-activated translation is the internal ribosome entry site (IRES)-driven initiation. IRESs, first discovered in viral mRNAs, are present in cellular mRNAs coding for master regulators of cell responses, whose expression must be tightly controlled. IRESs allow translation of these mRNAs in response to different stresses, including DNA damage, amino-acid starvation, hypoxia or endoplasmic reticulum stress, as well as to physiological stimuli such as cell differentiation or synapse network formation. Importantly, cellular mRNA IRESs are regulated by IRES trans-acting factor (ITAFs), exerting their action by at least nine different mechanisms. This review presents an update of the reported ITAFs regulating cellular mRNA translation and of the different mechanisms allowing them to control translation initiation in specific conditions. The impact of ITAFs on coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.
REVIEW | doi:10.20944/preprints202109.0167.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: extracellular vesicles; exosomes; microvesicles; apoptotic bodies; apoptotic extracellular vesicles; cell death; inflammation; sepsis; lung inflammatory disorders; SARS-CoV-2
Online: 9 September 2021 (10:31:49 CEST)
Extracellular vesicles (EVs) have been identified as novel mediators of intercellular communication. They work via delivering the sequestered cargo to cells in close vicinity as well as distant sites in the body, regulating pathophysiological processes. Cell death and inflammation are biologically crucial processes in both normal physiology and pathology. These processes are indistinguishably linked with their effectors modulating the other process. For instance, during an unresolvable infection, the upregulation of specific immune mediators leads to inflammation causing cell death and tissue damage. EVs have gained considerable interest as mediators of both cell death and inflammation during conditions such as sepsis. This review summarizes the types of extracellular vesicles known to date and their roles in mediating immune responses leading to cell death and inflammation with specific focus on sepsis and lung inflammation.
REVIEW | doi:10.20944/preprints201702.0020.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: alpha-synuclein; Parkinsons disease; dementia with Lewy bodies; multiple system atrophy; tunelling nanotube; glymphatic system; cell-to-cell spread
Online: 7 February 2017 (03:24:21 CET)
Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.
ARTICLE | doi:10.20944/preprints202201.0174.v1
Subject: Life Sciences, Other Keywords: alpha-synuclein; post-translational modifications; Parkinson’s disease; Multiple system atrophy; Lewy bodies; Lewy neurites; Glial cytoplasmic inclusions; phosphorylation; nitration; immunohistochemistry
Online: 12 January 2022 (14:31:13 CET)
Aggregated alpha-synuclein (-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of -synuclein exist, including phosphorylated and nitrated forms. It is unclear which -synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three -synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 -synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 -synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 -synuclein in MSA. Quantification of the LB scores revealed that pS129 -synuclein was the dominant and earliest -synuclein PTM followed by nY39 -synuclein, while lower amounts of pSer87 -synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.
ARTICLE | doi:10.20944/preprints201911.0399.v1
Subject: Life Sciences, Molecular Biology Keywords: olivo-ponto-cerebellar atrophy (OPCA); Purkinje cells; Calcium/calmodulin dependent protein kinase II (CAMK2); Plastin (Fimbrin); Hirano bodies; Huntington’s disease
Online: 30 November 2019 (14:47:30 CET)
Ataxin-2 (human gene symbol ATXN2, protein ATXN2) is the disease protein of Spinocerebellar Ataxia type 2 (SCA2). The large expansions of a polyglutamine (polyQ) stretch above a threshold of ~33 glutamines cause the multi-system nervous atrophy SCA2, while intermediate expansions of 29-32 glutamines contribute to the risk of the motor neuron diseases Amyotrophic Lateral Sclerosis (ALS) and Fronto-Temporal Lobar Dementia (FTLD). To elucidate the cellular function of ATXN2, we further characterized its direct interaction with alpha-Actinin-1 (symbol ACTN1), which had been observed in high-throughput yeast-two-hybrid surveys. An endogenous complex of ATXN2 and ACTN1 proteins was detected by co-immunoprecipitation. In vitro GST-tag pull-down experiments showed that the Calponin-Homology-domain at the N-terminus of ACTN1 binds to the N-terminus of ATXN2. Although an impact of the polyQ expansion on the interaction was not evident in pull-down experiments, a recent characterization of aged Atxn2-CAG100-KnockIn mice provides evidence. Both proteins associated in the cytosol and at the plasma membrane, as determined by sedimentation experiments in mouse brain, and by immunofluorescence microscopy of a transfected monkey cell line and of rat primary hippocampal neurons. In view of the roles of ACTN1 for spine plasticity and postsynaptic receptor control via reassembly of cortical actin, our data help to explain the impaired dendrite maintenance in SCA2.
REVIEW | doi:10.20944/preprints202110.0453.v3
Subject: Physical Sciences, General & Theoretical Physics Keywords: Matter; Consciousness; informational physics; fundamental physical problems; cosmology; quantum mechanics; relativity theories; Standard Model; particles; antiparticles; fundamental Nature forces; EM force; magnetic monopole; Gravity; quantum gravity; fast bodies mechanics; Lorentz transformations; spacetime; experimental testing
Online: 15 November 2022 (10:59:04 CET)
This article is some review of results that were obtained at 2007-2021 years development of “The Information as Absolute” concept and the informational physical model, which is based on the concept; including a number of fundamental physical problems are briefly considered in framework of the conception and the model. Recently in physics there are several publications, that present lists of the problems. However, those lists are essentially incomplete, for at least two reasons. Firsts of all, a number of phenomena are studied traditionally by philosophy, and so corresponding problems are usually considered to be “metaphysical”. However, they relate also to some concrete physical phenomena. For example, physics evidently studies Matter, and so the metaphysical problems “what is ontology of Matter”, “what is “Space”, “Time” and a few other physical phenomena and notions as well, are really a Meta-physical problem “what does physics study?” There are other fundamental physical problems, which are not considered as such in physics, and are absent in the “fundamental problems lists”. Those include the problems, which really exist, yet are incorporated into standard physical theories, and so are fundamental “implicitly”, which in physics are “solved by default”. Note, though, that a number of “Meta-physical”, and concrete fundamental, problems more in detail are considered in the paper “The Informational Conception and Basic Physics”, https://arxiv.org/abs/0707.4657, v5 (2021), so this paper is, in certain sense, an expanded conclusion of this paper, which includes, correspondingly, more in detail consideration of some more general physical problems, and, besides, in this [v3] version, the problem “what are Gravity and Electric Forces” is essentially clarified. Besides, the concrete problem “What is Life”, and the rational cosmological model, where a few vague points in standard cosmology rather probably are rationally clarified, while the fundamental problem “matter – antimatter asymmetry” in Matter is solved practically for sure, are considered, and one of recently published rather complete “lists of fundamental problems” is commented in Appendix.