The bacterial wilt pathogen, first known as Bacillus solanacearum, has undergone numerous taxonomic changes since its first description in 1896. The history and significance of this pathogen is covered in this review with an emphasis on the advances in technology that were used to support each reclassification that finally led to the current separation of Ralstonia solanacearum into three genomic species. Frequent name changes occurred as methodology transitioned from phenotypic, biochemical, and molecular studies, to genomics and functional genomics. The diversity, wide host range and geographical distribution of R. solanacearum has resulted in its inclusion in a “species complex” as genomic analyses of elucidated phylogenetic relationships among strains. Current advances in phylogenetics and functional genomics now open new avenues for research into the epidemiology and control of the devastating bacterial wilt disease.

The human angiotensin-converting enzyme 2 (ACE2) has a crucial role on blood pressure control; however, ACE2 is also the primary SARS-CoV-2 (S domain) virus receptor. Inhibiting or even reducing the expression of the native ACE2 might diminish the viral entry into the cells, but may cause a failure of ACE2 biological activity, primarily in patients with comorbidities, including diabetes mellitus or hypertension. Since the ACE2 catalytic site and the SARS-Cov-2 receptor are distinct, we designed a Crispr-Cas9 model system, predicting the respective sequences for a guide RNA (gRNA) and a single-stranded oligo dideoxy nucleotide (ssODN), to introduce point mutations into the exon 1 of the human ACE2 gene, which encodes the alpha-helix, implicated on the binding of the SARS-CoV-2 envelope S protein. Protein modeling predicted that the specific substitutions of residues Phe28, Lys31, and Tyr41 for Ala at the ACE2 alpha-helix do not significantly alter ACE2 native conformation. The analysis of the impact of these mutations on ACE2 receptor function predicted a weakening of the binding of the SARS-CoV-2 protein S. An experimental genome editing of cells based on these Crispr-Cas9 elements might reduce the SARS-CoV-2 ability to enter the epithelial cell, preserving the biological activity of ACE2 enzyme.

Tobacco Free Nicotine (TFN) Electronic Nicotine Delivery Systems (ENDS) are yet to be classified as tobacco products; consequently, there is ambiguity over whether Food and Drug Administration (FDA) regulatory authority can be extended to include TFN e-cigarettes. In recent years, a more significant number of e-cigarette companies have been manufacturing TFN-containing e-cigarettes and e-liquids to circumvent FDA regulations. While studies have shown that aerosols generated from tobacco-derived nicotine-containing e-cigarettes contain significant Reactive Oxygen Species (ROS) levels, no comparison studies have been conducted using TFN e-cigarettes. This study uses a single puff aerosol generator to aerosolize TFN and tobacco-derived nicotine-containing vape-products and subsequently involves semi-quantifying ROS generated by these vape products in H2O2 equivalents. We found that the differences between ROS levels generated from TFN and tobacco-derived nicotine-containing vape products vary by flavor. TFN tobacco flavors and fruit flavors are more toxic in terms of ROS generation than menthol/ice and drink/beverage flavored products using TFN. The type of salt nicotine used in vape products, TFN or tobacco-derived nicotine, impacts the level of ROS generated from flavored vape products. Thus, a better understanding of the type of salt nicotine used in e-cigarettes (tobacco-derived or synthetic), has modulating effect on lung oxidative stress.

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health. Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes. Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms. In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

Each year, the global population and agriculture suffer critical agricultural output losses as a result of severe drought devastation. Physiological drought occurs when plants are unable to extract water from the soil, even though it is available in the root zone. Apart from having a significant effect on plant physiology, drought stress has the effect of reducing crop yield. Drought stress influences plant metabolism both directly and indirectly. Drought stress alters the morpho-anatomical, physiological, and biochemical composition of plants, thereby decreasing transpiration water loss and increasing the efficiency with which plants use their water. Constant water loss through transpiration, combined with previously lost water, results in leaf water deficits. Nonetheless, drought stress has a wide variety of effects, ranging from lesions to confusion. Plant health is harmed when their ability to absorb water and nutrients, interact with their environment, and breathe is harmed. Apart from oxidative damage to plants, it may also result in cell death, which can occur under certain conditions when cells are exposed to their environment. Drought induces a plethora of physiological and molecular changes in plants, the majority of which assist them in adapting to the harsh environment. To mitigate drought's adverse effects, we must first gain a better understanding of how drought affects plant physiology. The purpose of this research is to better understand how drought affects plant development by examining the causes and effects of drought stress.

While the angiotensin converting enzyme 2 (ACE2) protein is defined as the primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, the viral serine molecule might be mobilized by the host's transmembrane protease serine subtype 2 (TMPRSS2) enzyme from the viral spike (S) protein and hijack the host’s N-acetyl-D-galactosamine (GalNAc) metabolism. The resulting hybrid, serologically A-like/Tn (T-nouvelle) structure potentially acts as a host–pathogen functional molecular bridge. In humans, this intermediate structure will hypothetically be replaced by ABO(H) blood group-specific, mucin-type structures, in the case of infection hybrid epitopes, implicating the phenotypically glycosidic accommodation of plasma proteins. The virus may, by mimicking the synthetic pathways of the ABO(H) blood groups, bind to the cell surfaces of the blood group O(H) by formation of a hybrid H-type antigen as the potential precursor of hybrid non-O blood groups, which does not affect the highly anti-glycan aggressive anti-A and anti-B isoagglutinin activities, exerted by the germline-encoded nonimmune immunoglobulin M (IgM). In the non-O blood groups, which have developed from the H-type antigen, these IgM activities are downregulated by phenotypic glycosylation, while adaptive immunoglobulins might arise in response to the hybrid A and B blood group structures, bonds between autologous carbohydrates and foreign peptides, suggesting the exertion of autoreactivity. The non-O blood groups thus become a preferred target for the virus, whereas blood group O(H) individuals, lacking the A/B phenotype-determining enzymes and binding the virus alone by hybrid H-type antigen formation, have the least molecular contact with the virus and maintain the critical anti-A and anti-B isoagglutinin activities, exerted by the ancestral IgM, which is considered the humoral spearhead of innate immunity.

The recent outbreak of Coronavirus Disease 2019 (COVID-19) is a major threat to human health and the global economy. In addition to the development of vaccines there is an urgent need for preventive and therapeutic strategies towards severe COVID-19. Key to this would be a better understanding of the molecular mechanismsoiuuuu affected by SARS-COV-2. To address this, we performed a systems biology approach by integrating available RNA-seq datasets from post-mortem lung tissue of COVID-19 patients and cell culture models infected with SARS-COV-2, Respiratory Syncytial virus or influenza virus. We identified two gene-expression modules that are commonly regulated by the three viral diseases and one that is specific to COVID-19. All 3 gene-expression modules represent key inflammatory processes. We identified several proteins within these networks that can be targeted by FDA approved drugs. Key examples are TNF, NFkB, INTERLEUKIN-1 and ALOX5 signaling pathways. Our data also suggest that Vitamin D supplementation and a ketogenic diet should be further analyzed as preventive strategies. In conclusion, our data highlights the potential of transcriptomics to unravel the pathological processes related to COVID-19 and guide the initiation of clinical trials.

SARS-CoV-2 causes severe pneumonia epidemics and probably originated in horseshoe bats, but the intermediate host is unknown. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from different species including cats, chimpanzees, dogs, cattles. Our results show, domestic cats (Felis catusc) and dogs (Canis lupus familiaris) are more susceptible to infection by SARS-CoV-2 and that they can efficiently transmit the virus to previously uninfected animals that are housed with them. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

Solanesol is a noncyclic terpene alcohol composed of nine isoprene units and it mainly accumulates in solanaceous plants, especially tobacco (Nicotiana tabacum L.). Here, RNA-seq analyses of tobacco leaves, stems, and roots were used to identify solanesol biosynthesis genes. Six 1-deoxy-d-xylulose 5-phosphate synthase, two 1-deoxy-d-xylulose 5-phosphate reductoisomerase, two 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase, four 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase, two 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase, four 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, two 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase, six isopentenyl diphosphate isomerase, and two solanesyl diphosphate synthase (SPS) genes were identified to be involved in solanesol biosynthesis. Furthermore, the two N. tabacum SPS (NtSPS1 and NtSPS2), which had two conserved aspartate-rich DDxxD domains, were highly homologous with SPS enzymes from other solanaceous plant species. In addition, the solanesol contents of three organs, and leaves from four growing stages, corresponded with the distribution of chlorophyll. Our findings provide a comprehensive evaluation of the correlation between the expression of different biosynthetic genes and the accumulation of solanesol in tobacco.

Inflammatory bowel diseases, which consist of chronic inflammatory conditions of the colon and the small intestine, are considered a global disease of our modern society. Recently, the interest toward the use of herbal therapies for the management of inflammatory bowel diseases has increased because of their effectiveness and favorable safety profile, compared to conventional drugs. Boswellia serrata Roxb. and Curcuma longa L. are amongst the most promising herbal drugs, however, their clinical use in inflammatory bowel diseases is limited and little is known on their mechanism of action. The aim of this work was to investigate the effects of two phytochemically characterized extracts of B. serrata and C. longa in an in vitro model of intestinal inflammation. Their impact on cytokine release and reactive oxygen species production, as well as the maintenance of the intestinal barrier function and on intestinal mucosa immune cells infiltration, has been evaluated. The extracts showed a good protective effect on the intestinal epithelium at 1 µg/ml, with TEER values increasing by approximately 1.5 fold, compared to LPS-stimulated cells. C. longa showed an anti-inflammatory mechanism of action, reducing IL-8, TNF-α and IL-6 production by approximately 30%, 25% and 40%, respectively, compared to the inflammatory stimuli. B. serrata action was linked to its antioxidant effect, with ROS production being reduced by 25%, compared to H₂O₂-stimulated Caco-2 cells. C. longa and B. serrata resulted to be promising agents for the management of inflammatory bowel diseases by modulating in vitro parameters which have been identified in the clinical conditions.

Traditional methods for discovery and development of new drugs can be a very time-consuming and expensive process because it includes several stages such as compound identification, pre-clinical and clinical trials before the drug is approved by the US Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug Zidovudine for the treatment of Dry Age-Related Macular Degeneration and the antidepressant Imipramine for Small-Cell Lung Carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that Imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in-silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.

Background: Capsaicinoid are a group of compounds and widely used in the food, medical, and pharmaceutical industries. Capsaicinoid are unique synthesized and accumulated in the pepper fruits. MeJA can enhance the capsaicinoid production. Temporal and spatial expression of capsaicinoid biosynthetic genes are helpful to understand the molecular mechnism of capsaicinoid biosynthesis in the fruits of pepper. Although some of the capsaicinoid biosynthetic genes in pepper have been identified, the expression of these genes at different developing stages of fruit has not been systemically investigated, and little is known about the molecular basis of MeJA inducing capsaicinoid biosynthesis. Results: HPLC study revealed that the capsaicinoid accumulation in the developing fruit of pepper initially appeared at 24 DAP (day after pollination), was actively development at 36 DAP and peaked at 48 DAP. 11 genes that encoded enzymes involved in capsaicinoid biosynthesis were isolated and characterized. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that the CaCS was unique expressed in placenta and the other 10 genes were expressed in all selected tissues and 9 of 11 genes (except CaCa4H and CaCa3H) were strongly expressed in placenta tissue. Spatial expression analysis demostrated that the 11 gene could be collectively grouped into four categories based on the patterns of relative expression of the genes during fruit development. Category I has 2 and they displayed a bell-shaped expression pattern with the peak expression at 24 DAP, Category II contains 5 genes and expression of the 5 genes was constantly increased from 0 to 36 DAP and peaked at 36 DAP. Category III comprises of 2 genes and both genes reached the peak at 48 DAP. Category IV consists of 2 genes and they showed a high expression at 36 and 48 DAF, but unexpressed from 0 to 12 DAP. The gene expressions of the 11 genes were up-regulated by MeJA. 3 genes showed a high expression at 24 h; 4 genes reached the peak at 12 h; the top expression were observed at 18 h; The last one, CaACYase, achieved the highest level at 8 h. Conclusion: The biosynthesis of capsaicinoid in pepper fruit is developmentally regulated. The expression of the majority of capsaicinoid biosynthetic genes is highly consistent with the development accumulation of capsaicinoid in pepper fruit. These results not only provide the initial information on spatial and temporal expression of capsaicinoid biosynthetic genes in pepper developing fruit, but are also valuable to identify the MeJA-induced genes for capsaicinoid biosynthesis and accumulation during pepper fruit development.

Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promote the reactive oxygen species (ROS) production leading to airway inflammation, hyper-responsiveness and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long acting β2 agonists (LABAs; salmeterol and formoterol) and a new extra-LABA (indacaterol). The human monocyte cell line THP-1 cells were pre-treated with different concentrations of the asthma medications at different time-points after hydrogen peroxide (H₂O₂) stimulation. H₂O₂ production was measured with DCFH-DA by flow cytometry. Montelukast, fluticasone and salmeterol suppressed H₂O₂-induced ROS production. Indacaterol enhanced H₂O₂-induced ROS production. Budesonide and formoterol alone had no anti-ROS effects, but the combination of these two drugs significantly suppressed H₂O₂-induced ROS production. Different asthma medications have different anti-ROS effects on monocytes. The combination therapy with LABA and ICS seemed not be the only choice for asthma control. Montelukast may be also a good supplemental treatment for the poorly-controlled asthma because of its powerful anti-ROS effects. Our findings provide a novel therapeutic view in asthma.

All life on Earth uses three integrated molecular systems in which genetic information contained in DNA base sequences is transmitted to ribosomes by RNA and a genetic code, then translated into the amino acid sequences of structural and catalytic proteins. Therefore, the most important point for understanding the origin of life is to determine how such systems could emerge from random processes on the early Earth. In this review, two alternatives are compared: the RNA world hypothesis and the [GADV]-protein world hypothesis. [GADV] refers to four amino acids, Gly [G], Ala [A], Asp [D] and Val [V] that are conserved in the amino acid sequences of many common proteins. Here I will argue that the origins of the three primary processes required for life to begin can be better explained by the GADV hypothesis than the RNA world hypothesis. The GADV hypothesis also incorporates a conversion process by which random polymers can evolve into proteins with ordered sequences.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

BACKGROUND: Chronic hepatitis B infected with Hepatitis B virus remains a major health concern worldwide. Despite standard interferon-α and nucleotide analogues have been shown to reduce the deterioration of liver disease among chronic hepatitis B patients, covalently closed circular DNA was still difficult to eradicate. METHODS: A literature search of Pubmed and Web of science was performed with the following key words: ‘CRISPR’, ‘CRISPR/Cas9’, ‘hepatitis B’, ‘HBV’, ‘chronic hepatitis B’ and ‘HBV cccDNA’. The information about CRISPR/Cas9 for the treatment of HBV cccDNA or hepatitis B was reviewed. RESULTS: CRISPR/Cas9 could treat hepatitis B through suppressing or clearing HBV cccDNA with different gRNAs. CONCLUSION: With the emergence of CRISPR/Cas9 (the RNA-guided clustered regulatory interspaced short palindromic repeats, CRISPR) editing technology, clearance of hepatitis B virus and better prevention of liver carcinoma seemed to be possible.

Build a special identical equation, use its calculation characters to prove and search for solution of any odd converging to 1 equation through (*3+1)/2^k operation, change the operation to (*3+2^m-1)/2^k, and get a solution for this equation, give a specific example to verify. Thus prove the Collatz Conjecture is true. Furthermore, analysis the sequences produced by iteration calculation during the procedure of searching for solution, build a weight function model, prove it decrease progressively to 0, build a complement weight function model, prove it increase to its convergence state. Build a (*3+2^m-1)/2^k odd tree, prove if odd in (*3+2^m-1)/2^k long huge odd sequence can not converge, the sequence must outstep the boundary of the tree after infinite steps of (*3+2^m-1)/2^k operation.

Electricity price forecasting has become a crucial element for both private and public decision-making. This importance has been growing since the wave of deregulation and liberalization of energy sector worldwide late 1990s. Given these facts, this paper tries to come up with a precise and flexible forecasting model for the wholesale electricity price for the Italian power market on an hourly basis. We utilize artificial intelligence models such as neural networks and bagged regression trees that are rarely used to forecast electricity prices. After model calibration, our final model is bagged regression trees with exogenous variables. The selected model outperformed neural network and bagged regression with single price used in this paper, it also outperformed other statistical and non-statistical models used in other studies. We also confirm some theoretical specifications of the model. As a policy implication, this model might be used by energy traders, transmission system operators and energy regulators for an enhanced decision-making process.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

XGBoost is recognized as an algorithm with exceptional predictive capacity. Models for a binary response indicating the existence of accident claims vs. no claims can be used to identify the determinants of traffic accidents. We compare the relative performances of logistic regression and XGBoost approaches for predicting the existence of accident claims using telematics data. The dataset contains information from an insurance company about individuals’ driving patterns – including total annual distance driven and percentage of total distance driven in urban areas. Our findings show that logistic regression is a suitable model given its interpretability and good predictive capacity. XGBoost requires numerous model-tuning procedures to match the predictive performance of the logistic regression model and greater effort as regards interpretation.

Global climate change requires urgent solutions. Ambitious tree-planting initiatives, many already underway, aim to sequester enormous quantities of carbon, partly compensating for the anthropogenic CO₂ emissions that are a major cause of rising global temperatures. However, poorly planned and executed tree-planting could actually increase CO₂ emissions and have long-term, deleterious impacts on biodiversity, landscapes and livelihoods. Here, we highlight the main environmental risks of large-scale tree planting and propose ten golden rules, based on some of the most recent ecological research, to implement forest ecosystem restoration that maximizes rates of both carbon sequestration and biodiversity recovery, while simultaneously improving livelihoods. These are: i) Protect existing forest first; ii) Work together (involving all stakeholders); iii) Maximize biodiversity recovery to meet multiple goals; iv) Select appropriate areas; v) Use natural regeneration wherever possible; vi) Select species to maximise biodiversity; vii) Use resilient plant material (with appropriate genetic variability and provenance); viii) Plan ahead for infrastructure, capacity and seed supply; ix) Learn by doing (using an adaptive management approach); and x) Make it pay (ensuring the economic sustainability of the project). We focus on the design of long-term strategies to tackle the climate and biodiversity crises and support livelihood needs. We emphasize the role of local communities and their dependence on benefits from successful reforestation programmes that restore ecosystem functioning and deliver a diverse range of forest products and services. While there is no simple and universal recipe for forest restoration, it is now crucial to build on the public and private interest in this topic to ensure interventions provide effective, long-term carbon sinks and maximise benefits for biodiversity and people.

One of the most common and important destructive attacks on the victim system is Advanced Persistent Threats (APT)-attack. The APT attacker can achieve his hostile goals by obtaining information and gaining financial benefits regarding the infrastructure of a network. One of the solutions to detect a secret APT attack is using network traffic. Due to the nature of the APT attack in terms of being on the network for a long time and the fact that the network may crash because of high traffic, it is difficult to detect this type of attack. Hence, in this study, machine learning methods such as C5.0 decision tree, Bayesian network and deep neural network are used for timely detection and classification of APT-attacks on the NSL-KDD data set. Moreover, 10-fold cross validation method is used to experiment these models. As a result, the accuracy (ACC) of the C5.0 decision tree, Bayesian network and 6-layer deep learning models is obtained as 95.64%, 88.37% and 98.85%, respectively, and also, in terms of the important criterion of the false positive rate (FPR), the FPR value for the C5.0 decision tree, Bayesian network and 6-layer deep learning models is obtained as 2.56, 10.47 and 1.13, respectively. Other criterions such as sensitivity, specificity, accuracy, false negative rate and F-measure are also investigated for the models, and the experimental results show that the deep learning model with automatic multi-layered extraction of features has the best performance for timely detection of an APT-attack comparing to other classification models.

Aflatoxin contaminates foods including peanuts. Aflatoxin is a carcinogenic toxin mainly produced bty Aspergillus flavus. Other Aspergillus species that rarely produce aflatoxins are A. nomius and A. niger. Aflatoxin is associated with liver failure, hepatocellular carcinoma (HCC) and death. Recent studies have shown that peanuts in Kenya are highly contaminated with aflatoxins but information gaps exist on the characterization of the Aspergillus species that produce aflatoxins in peanuts in Kenya. Therefore, this gap necessitated the determination of the Aspergillus species producing aflatoxins in peanuts from the main growing districts of Busia and Kisii Central districts. One hundred and two (102) peanuts samples were collected from farmers’ in each district Aspergillus species were isolated from the peanut samples by using the dilution plate technique on modified Rose Bengal agar. Phenotypical characterization of the identified Aspergillus section flavus isolates from the peanuts samples was determined using the procedure of Mellon and Cotty. This study identified five (5) Aspergillus species as contaminants in peanuts analyzed in this study. They were Aspergillus flavus L-strain, Aspergillus flavus S-strain, Aspergillus parasiticus, Aspergillus niger and Aspergillus tamari. Overall, the occurrence of Aspergillus flavus L- strain and A. flavus S- strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species identified in the study with a mean occurrence of 45.1%. Aspergillus flavus L- strain was the most common isolate (58.8%) in peanuts from Busia district while A. flavus S- strain was the most common strain (60.2%) in peanuts from Kisii Central district. Overall, the occurrence of Aspergillus flavus L strain and A. flavus S strain were significantly higher than other species identified (H = 15.55, df = 4, P = 0.004) in peanuts from the two districts. However, A. flavus S-strain was the most dominant species (F=3.15, df =25, P=0.031) with an overall mean occurrence of 45.1%. The confirmation of occurrence of other species that produce toxins such as A. niger and A. tamarii which also produces cyclopiazonic acid suggests the need to screen peanuts for other carcinogenic mycotoxins.

The present study was performed to examine that transforming growth factor beta (TGF-β) in root-surrounding tissues on deciduous teeth during the physiological root resorption regulates the differentiation induction into odontoclast. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1-R3 or N1-N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1-N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for RANKL-mediated osteoclast differentiation revealed that TGF-β in N1-N3 and R1-R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA level of TGF-β1 in N1 and N2 was significantly increased, and corresponded with that of osteoprotegerin (OPG). In contrast, the expression level of receptor activator of NF-κB ligand (RANKL) was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

Cistanthe subspeciosa Hershk. (Cistanthe Spach sect. Cistanthe; Montiaceae) here is described as a herbaceous to suffruticose perennial from the vicinity of Copiapó, Chile. Its epithet is juxtaposed with its rank in order to highlight its subspecific aesthetic. In particular, the specioid is infrequent, locally restricted, and lacks unique diagnostic traits. Rather, it is diagnosed by a combination of traits characteristic of different Cistanthe species from the region, none of which can be identified as the referential species to which Cs. subspeciosa might be considered subspecific. The intersection between species nomenclature and species ontology thus is discussed. I hypothesize that Cs. subspeciosa is irrigated primarily by mountain runoff rather than localized precipitation, and that it might be both resistant to and dependent upon high substrate metal concentrations characteristic of the Copiapó region. The ornamental value of this and other Cistanthe species is discussed. Finally, additional historical details pertaining to Calandrinia spectabilis Otto & Dietr. and Cistanthe philhershkovitziana are provided.

Arthropod predators preying on vertebrates is generally overlooked in ecological studies, as it is not typically observed in nature and generally considered a rare event. This is likely due to the cryptic nature of these predatory events, the relatively small size of arthropods, and the difficulty in collating published data which is scattered throughout the literature. Although arthropods are known to readily hunt and consume vertebrates, very little is known about these predatory events. In this study, a systematic literature review was conducted to provide a conceptual framework, identify global patterns, and create a searchable database of arthropod preying on vertebrates. This study represents the largest global assessment of arthropod predators and vertebrate prey with over a thousand recorded observations collated from over 80 countries across every continent except Antarctica, where no arthropod predator exists. Arthropod predators were represented by six classes (insects, arachnids, centipedes, and crustaceans: Malacostraca, Ostracoda, Hexanauplia) and over 80 families. Vertebrate prey were represented by five classes (birds, mammals, reptiles, amphibians, fish) and 160 families. The most common prey were frogs consisting of over a third of all observations. The most commonly preyed reptiles were nearly all lizards, half of mammal prey were bats, nearly a third of fish were Cypriniformes, and half of bird prey were passerines. Spiders represented over half of all predatory events found and were the main predator for all vertebrates except birds, which were preyed mostly upon praying mantises. However, prey varied between spider families. For insects, true bugs (Hemiptera) and beetles preyed mostly on amphibians while the aquatic Odonata larvae preyed on amphibians and fish. Decapod predators were observed preying equally between reptiles, birds, and amphibians; with centipedes preying mainly on reptiles and mammals. Predation was mostly recorded from the Americas and Australia, with countries and regions varying between predator and prey groups. This study demonstrates that arthropods are indeed an overlooked predator of vertebrates. Recognizing and quantifying these predator-prey interactions is vital for identifying patterns and the potential impact of these relationships on shaping vertebrate populations and communities. Understanding the possible threat of arthropod predators may be especially important to improve the success of conservation efforts by accounting for predators which may currently be overlooked.

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydoxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by significant decrease in non enzymatic antioxidants and TAS concentrations. 8-OHdG and cell proliferation level were negatively correlated with non enzymatic antioxidants viz., Vitamin A, Vitamin C, vitamin E level and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity amongst the malignant, benign and controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. Among the oxidative stress markers and cell proliferation index, decreased level of vitamin A, vitamin C, vitamin E, TAS and increased level of 8-OHdG, cell proliferation index emerged as best predicted biomarkers for subjects with malignancy and benign breast disease.

MicroRNAs (miRNAs) are a kind of conserved small non-coding RNAs that participate in regulating gene expression by targeting multiple molecules. Early studies have shown that the expression of miRNAs changes significantly in different tumor tissues and cancer cell lines. It is well acknowledged that such variation is involved in almost all biological processes, including cell proliferation, mobility, survival and differentiation. Increasing experimental data indicate that miRNA dysregulation is a biomarker of several pathological conditions including cancer, and that miRNA can exert a causal role, as oncogenes or tumor suppressor genes, in different steps of the tumorigenic process. Anticancer therapies based on miRNAs are currently being developed with a goal to improve outcomes of cancer treatment. In our present study, we review the function of miRNAs in tumorigenesis and development, and discuss the latest clinical applications and strategies of therapy targeting miRNAs in cancer.

Ectopic expression of the MYB transcription factor of AmROSEA1 from Antirrhinum majus has been reported to change anthocyanin and other metabolites in several species. In this study, we found that overexpression of AmRosea1 significantly improved the tolerance of transgenic rice to drought and salinity stress. Transcriptome analysis revealed that a considerable amount of stress-related genes were affected by exogenous AmRosea1 during both drought and salinity stress treatments. These affected genes are involved in stress signal transduction, the hormone signal pathway, ion homeostasis and the enzymes that remove peroxides. This work suggests that the AmRosea1 gene is a potential candidate for genetic engineering of crops.

Understory plants are important components of forest ecosystem productivity and diversity. Compared to biomass models of overstory canopy trees, few are available for understory saplings and shrubs and therefore their roles in estimation of forest carbon pools are often ignored. In this study, we harvested 24 understory species including 4 saplings, 9 tree-like shrubs and 11 typical shrubs in coniferous and broadleaved mixed forest in northeastern China and developed the best fit allometric equations of above- and below-ground and total biomass by species-specific or multispecies using morphological measurements of basal diameter, height and crown area as independent variables. The result showed that single basal diameter, height or crown area had good explanatory power for both species-specific and multispecies (p<0.001). The best-fit models included only basal diameter in sapling and tree-like shrubs, and combinations of crown area, height, and basal diameter in typical shrubs. The logarithmic model was most desired among the 4 model forms of linear, quadratic, multiple linear and logarithmic, for species-specific and multispecies. The models we developed should help the estimation of forest ecosystem carbon stocks, especially for belowground component, and provide tools for quantification of individual species biomass of understory plants.

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

Genome-wide epigenetic changes in plants are being reported during the development and environmental stresses, which are often correlated with gene expression at the transcriptional level. Sum total of the biochemical changes in nuclear DNA, post-translational modifications in histone proteins and variations in the biogenesis of non-coding RNAs in a cell is known as epigenome. These changes are often responsible for variation in expression of the gene without any change in the underlying nucleotide sequence. The changes might also cause variation in chromatin structure resulting into the changes in function/activity of the genome. The epigenomic changes are dynamic with respect to the endogenous and/or environmental stimuli which affect phenotypic plasticity of the organism. Both, the epigenetic changes and variation in gene expression might return to the pre-stress state soon after withdrawal of the stress. However, a part of the epigenetic changes may be retained which is reported to play role in acclimatization, adaptation as well as in the evolutionary processes. Understanding epigenome-engineering for improved stress tolerance in plants has become essential for better utilization of the genetic factors. This review delineates the importance of epigenomics towards possible improvement of plant’s responses to environmental stresses for climate resilient agriculture.

We investigated and quantified bacterial accumulation in facemasks used by the general population, using 16S rRNA (Sanger Sequencing), culture and biochemical analysis along with Rose Bengal staining. Additionally, a systematic overview of the literature on face mask contamination was undertaken. We found an average bacterial load of 4.24 × 10⁴ CFU recovered/mask, with a maximum load of 2.85 × 10⁵ CFU. This maximum is 310 times higher than the limit value for contamination of ventilation system outlet surfaces specified by the German standard VDI 6022. Biochemical and molecular identification predominantly found Staphylococcus species (80%), including Staphylococcus aureus, along with endospore-forming Bacillus spp. Literature reports also indicate contamination of masks by bacterial and fungal opportunists of the genera Acinetobacter, Aspergillus, Alternaria, Bacillus, Cadosporium, Candida, Escherichia, Enterobacter, Enterococcus, Klebsiella (including K. pneumoniae), Micrococcus, Microsporum, Mucor, Pseudomonas, Staphylococcus and Streptococcus. Bacterial counts increase linearly with wearing duration, and prolonged use may affect the skin and respiratory microbiomes, promoting consequential eye, skin, oral and airway conditions. These aspects underscore the urgent need for further research and a risk-benefit analysis in respect of mask use, particularly given their unproven efficacy in disrupting the transmission of respiratory viruses and their adverse social consequences.

With the global climate anomalies and the destruction of ecological balance, water shortage has become a serious ecological problem facing all mankind, and drought has become a key factor restricting the development of agricultural production. Therefore, it is essential to study the drought tolerance of crops. On the basis of previous studies, we reviewed the effects of drought stress on plant morphology and physiology, including the changes of external morphology and internal structure of root, stem and leaf, the effects of drought stress on osmotic regulation sub-stances, drought-induced proteins and active oxygen metabolism of plants. In this paper, the main drought stress signals and signal transduction pathways in plants are described, and the functional genes and regulatory genes related to drought stress are listed respectively. We summarize the above aspects in order to provide valuable background knowledge and theoret-ical basis for future agriculture and forestry breeding and cultivation.

Phytophthora. infestans is a well known late blight causing oomycetes pathogen. It evolves and adapts to the host background and new fungicide molecules rapidly within a few years of their release, may be due to the predominance of transposable elements in its genome. Frequent and huge applications of fungicides cause environmental concerns. Here we developed target specific RNA interference based molecules, that are capable of effectively reducing the late blight infection. cDNA microarray expression data was used for the selection of genes involved in the early stage of infection process, sporulation etc. The in vitro synthesis of double stranded RNA molecule, targeting SDH, EF-1α, GPI-HAM344, PLD-3 and HSP-90 encoding genes revealed the reduction in growth, sporulation and symptom expression, which were subsequently assessed by culture bioassay, detached leaf assay and topical application methods. The multiple genes targeted dsRNA nano clay sprayed plants showed enhanced disease resistance (4% disease severity) and least sporulation (<1x103), compared to naked dsRNA spray. Use of nano clay was assumed to be involved in the effective delivery, protection and boosting the action of RNAi in potato plants. A significant difference in the growth, sporulation count, disease severity and reduced expression of the genes and confocal microscopy imaging authenticates the effects of SIGS on late blight disease progression. Our research demonstrated that topical dsRNA nano clay spray under the open-air environment could be an alternative to chemical fungicides and transgenic approaches as a novel plant protection strategy for late blight in an environmentally friendly manner.

Human microbiome data from genomic sequencing technologies is fast accumulating, giving us insights into bacterial taxa that contribute to health and disease. Predictive modeling of such microbiota count data for classification of human infection from parasitic worms such as helminths can help in detection and management across global populations. Real-world datasets of microbiome experiments are typically sparse containing hundreds of measurements for bacterial species, of which only a few are detected in the bio-specimens that are analyzed. This feature of microbiome data produces the challenge of needing more observations for accurate predictive modeling and has been dealt with previously using different methods of feature reduction. To our knowledge, integrative methods such as transfer learning has not been explored in the microbiome domain yet, as a way to deal with data sparsity by incorporating knowledge of different but related datasets. One way of incorporating this knowledge is by using a meaningful mapping among features of these datasets. In this paper, we claim that this mapping would exist among members of each individual cluster grouped based on phylogenetic dependency among taxa and their association to the phenotype. We validate our claim by showing that models incorporating associations in such a grouped feature space result in no performance deterioration for the given classification task. In this paper, we test our hypothesis using classification models that detect helminth infection in microbiota of human fecal samples obtained from Indonesia and Liberia countries. In our experiments, we first learn binary classifiers for helminth infection detection by using Naive Bayes, Support Vector Machines, Multilayer Perceptrons, and Random Forest methods. In the next step, we add taxonomic modeling using the SMART-scan module to group the data, and learn classifiers using the same four methods, to test the validity of the achieved groupings. We observed a 6% to 23% and 7% to 26% performance improvement based on the Area Under ROC Curve (AUC) and Balanced Accuracy(Bacc) measures, respectively, over 10 runs of 10-fold cross-validation. These results show that using phylogenetic dependency for grouping our microbiota data actually results in a noticeable improvement in classification performance for helminth infection detection. These promising results from this feasibility study demonstrate that methods such as SMART-scan can be utilized in the future for knowledge transfer from different but related microbiome datasets by phylogenetically-related functional mapping, to enable novel integrative biomarker discovery.

Clock Network Design (CDN) is a critical step while designing any Integrated-Circuits (ICs). It holds vital importance in the performance of entire circuit. Due to continuous scaling, 3D ICs stacked with TSV are gaining importance, with an objective to continue with the Moore's law. Through-Silicon-Via (TSV) provides the vertical interconnection between two die, which allows the electrical signal to flow through it. 3D ICs has many advantages over conventional 2D planar ICs like reduced power, area, cost, wire-length etc. The proposed work is mainly focused on power reduction and obstacle avoidance for 3D ICs. Various techniques have already been introduced for minimizing clock power within specified clock constraints of the 3D CND network. Proposed 3D Clock Tree Synthesis (CTS) is a combination of various algorithms with an objective to meet reduction in power as well as avoidance of obstacle or blockages while routing the clock signal from one sink to other sink. These blockages like RAM, ROM, PLL etc. are fixed during the placement process. The work is carried out mainly in three steps- first is Generation of 3D Clock tree avoiding the blockages, then Buffering and Embedding and finally validating the results by SPICE simulation. The experimental result shows that our CTS approach results in significant 9% reduction in power as compare to the existing work.

Testing in animals is mandatory in drug testing and the gold standard for evaluation of toxicity. This situation is expected to change in the future because the 3Rs principle, which stands for replacement, reduction and refinement of the use of animals in science, is reinforced by many countries. On the other hand, technologies for alternatives to animals experiments have increased. The necessity to develop and use of alternatives is influenced by the complexity of the research topic and also by the fact, to which extent the currently used animal models can mimic human physiology and/or exposure. Rodent lung morphology and physiology differs markedly for that of humans and inhalation exposure of the animals are challenging. In vitro and in silico methods can assess important aspects of the in vivo action, namely particle deposition, dissolution, action at and permeation across the respiratory barrier and pharmacokinetics. Out of the numerous homemade in vitro and in silico models some are available commercially or open access. This review discusses limitations of animal models and exposure systems and proposes a panel of in vitro and in silico techniques that, in the future, may replace animal experimentation in inhalation testing.

The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and non-invasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected sub-cutaneously with Matrigel™ to generate so called pseudo tumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 hours after heating. We showed that dextran-coated magnetic iron oxide nanoparticles dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as non-invasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

The increasingly affordable price point of terrestrial laser scanners has led to a democratization of instrument availability, but the most common low-cost instruments have yet to be compared in terms of the consistency to measure forest structural attributes. Here, we compared two low-cost terrestrial laser scanners (TLS): the Leica BLK360 and the Faro Focus 120 3D. We evaluate the instruments in terms of point cloud quality, forest inventory estimates, tree-model reconstruction, and foliage profile reconstruction. Our direct comparison of the point clouds showed reduced noise in filtered Leica data. Tree diameter and height were consistent across instruments (4.4% and 1.4% error, respectively). Volumetric tree models were less consistent across instruments, with ~29% bias, depending on model reconstruction quality. In the process of comparing foliage profiles, we conducted a sensitivity analysis of factors affecting foliage profile estimates, showing a minimal effect from instrument maximum range (for forests less than ~50 m in height) and surprisingly little impact from degraded scan resolution. Filtered unstructured TLS point clouds must be artificially re-gridded to provide accurate foliage profiles. The factors evaluated in this comparison point towards necessary considerations for future low-cost laser scanner development and application in detecting forest structural parameters.

The world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

Adaptive radiations occur mostly in response to environmental variation through the evolution of key eco-morphological innovations that allow emerging species to occupy new ecological niches. However, rapid phenotypic evolution and the evolution of key novelties are likely to also occur when a couple or few species are engaged into narrow ecological interactions. To demonstrate coevolution is a difficult task; only elusive evidences confirm that coevolution is a driver of speciation and diversification. Here we propose that the adaptive radiation of the Mediterranean orchid genus Ophrys, which gave rise to ca. 350 species since the apparition of the genus is due to the particular co-evolutionary dynamics between these plants and their pollinators. We suggest that the pollination by sexual swindle used by Ophrys orchids is the main driver of this coevolution. Flowers of each Ophrys species mimic sexually receptive females of one particular insect species, mainly bees. Male bees are attracted by pseudo-pheromones emitted by Ophrys flowers that are similar to the sexual pheromones of their females. Males lured by the flower shape, color and hairiness attempt to copulate with the flower, which glues pollen on their bodies. Pollen is eventually transferred to the stigma of another flower of the same Ophrys species during similar copulation attempts. Three observations led us to propose the scenario of an asymmetric co-evolutionary relationship between Ophrys and their pollinators. Firstly, there is a strong intra-specific competition among Ophrys individuals for the attraction of their species-specific pollinators, which is due to the high learning and memorization abilities of bees that record the pheromone signatures of kin or of previously courted partner to avoid (further) copulation attempts. Mnemonic pollinators induce thus a strong selective pressure for variation in the pseudo-pheromones emitted by individual flowers, which will potentially generate shifts in pollinator species, and hence Ophrys speciation. These pollinator shifts are adaptive for new Ophrys species because they may benefit from a competitor-free space. Secondly, such shifts in pollinator species are due to the random crossing of peaks in the olfactory landscape of the pollinator guild that is syntopic to each particular Ophrys population. This selective process on individual, random variation in pseudo-pheromone bouquets is followed by directional selection on flower phenotypes that will reinforce the attraction of the new pollinator. Thirdly, pollinators use the pseudo-pheromones emitted by Ophrys to locate suitable habitats from a distance within complex landscapes. Pollinators stay fixed for a while in these habitats by the local diversity of pseudo-pheromones, which increases their probability of encounter with a receptive female and hence the reproduction probability of both sexes. Conversely, pollinators disperse out of small suitable habitats once they have memorized the local diversity of sexual pseudo-pheromone bouquet or if fecundated Ophrys flowers repel pollinators, which decreases the probability of geitonogamy (plant advantage) but limit pollinator mating with locally emergent insect females, thus limiting inbreeding and favoring gene flow (pollinator advantage). Finally, we propose several research avenues that emerged according to this scenario of adaptive radiation by assymetric coevolution between Ophrys species and their pollinators.

How did life begin on Earth? And is there life elsewhere in the Cosmos? Challenging questions, indeed. The series of conferences established by NoR CEL in 2013, addresses these very same questions. The basis for this paper is the summary report of oral presentations that were delivered by NoR CEL’s network members during the 2018 Athens conference and, as such, disseminates the latest research which they have put forward. More in depth material can be found by consulting the contributors referenced papers. Overall, the outcome of this conspectus on the conference demonstrates a case for the existence of “probable chemistry” during the prebiotic epoch.

Among the plant nutrients potassium (K) is one of the vital elements required for plant growth and physiology. Potassium is not only a constituent of plant structure but also plays regulatory function in several biochemical processes related to protein synthesis, carbohydrate metabolism, enzyme activation. There are several physiological processes like stomatal regulation and photosynthesis are dependent on K. In the recent decades K was found to provide abiotic stress tolerance. Under salt stress, K helps in maintaining ion homeostasis and regulation of osmotic balance. Under drought stress condition K regulates the stomatal opening and makes the plants adaptive to water deficit. Many reports provided the notion that K enhances the antioxidant defense in plants and therefore, protects the plants from oxidative stress under various environmental adversities. Also, it provides some cellular signaling alone or in association with other signaling molecules and phytohormones. Although a considerable progress in understanding K-induced abiotic stress tolerance in plants has been achieved the exact molecular mechanisms of such protections are still under research. In this review, we summarized the recent literature on the biological functions of K, its uptake, and translocation and its role in plant abiotic stress tolerance.

We evaluated the potential of using fish species and functional traits as indicators of land use impacts to fish assemblages. We used environmental data collected at multiple spatial scales (local, reach, and upstream catchment) for 19 tributary and main stem sites in the Nolichucky River watershed in Tennessee. Canonical correspondence analyses showed that temperature, elevation, specific conductivity, sediment yield, impervious surfaces, and row crop cover at the catchment scale were strongly associated with fish assemblage structure, as well as forest cover from all three spatial scales. Blocked indicator species analysis, with stream size as the block, showed that significantly strong indicators of the least-impacted riparian land use condition (≥60% forest cover) were Saffron Shiner (Notropis rubricroceus), Rainbow Trout (Oncorhyncus mykiss), Longnose Dace (Rhynichthys cataractae), Creek Chub (Semotilus atromaculatus), and Mottled Sculpin (Cottus bairdi). Traits indicative of the least-impacted sites were the herbivorous trophic guild, mean female age-at-maturity, longevity, rock-gravel spawners, montane geology and pelagic swimmers. Specific conductivity was strongly related to multiple catchment-scale land use variables, and was a strong local-scale influence on fish assemblage structure. Our results show promise for using a relatively common but endemic southern Appalachian fish species, the Saffron Shiner, as an indicator for land-use related impacts to these streams.

Supplier selection is an important part of supply chain management (SCM) for any organisation to achieve their objectives. The problem has attracted great interest from academics and practitioners. The selection process starts with determining the most important criteria out of a wide range. Many academic researchers apply multi-criteria decision-making (MCDM) techniques for supplier selection. However, the complexity of such approaches may increase significantly, especially when considering a large number of suppliers and selection criteria. This paper proposes an integrated approach combining machine learning classification with the Analytic Hierarchy Process (AHP) to select and evaluate the most suitable supplier. A Decision Tree (DT) classifier is used to select the most important criteria, instead of applying AHP on the complete set of criteria. The applicability of the approach is demonstrated using data from Libyan companies. Results show that decision trees can successfully lead to a most important subset of selection criteria, which would lead to a less complex application of AHP.

The oxidative stress is one of the main cause for cardiovascular diseases (like Hypertension) also one of the results of these diseases. This study involved 56 subjects matched ages and sex divided into two groups; 28 hypertensive subject and 28 healthy subject as control group. The following analysis was done: 4-Hydroxy-2-nonenal(4HNE) and albumin. The results show that there is a significant increase in (4HNE) between patients group and control group. The increase in 4HNE which is a product of lipid peroxidation is attributed to destruction in body cell caused by due to the increase in stress events. It has been concluded that is important nappy on ideal weight, because obesity considered main factors for heart disease and hardening of the arteries. The aim of this study was to investigate the relationship between of some oxidative stress markers and cardiovascular diseases.

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

RNA-guided genomic transcriptional regulation tools, namely Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) and CRISPR-mediated gene activation (CRISPRa), are a powerful technology for the field of functional genomics. Deriving from the CRISPR/Cas9 system, both systems comprise a catalytically dead Cas9 (dCas9) and a single guide RNA (sgRNA). This type of dCas9 is incapable of cleaving DNA but retains its ability to specifically bind to DNA. The binding of the dCas9/sgRNA complex to a target gene results in transcriptional interference. The CRISPR/dCas9 system has been explored as a tool for transcriptional modulation and genome imaging. Despite its potential applications and benefits, the challenges and limitations faced by the CRISPR/dCas9 system include the off-target effects, PAM sequence requirement, efficient delivery methods, and the CRISPR/dCas9-interfered crops being labeled as genetically modified organisms in several countries. This review highlights the progression of CRISPR/dCas9 technology as well as its applications and potential challenges in crop improvement.

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.

Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim of this study was to identify mutations in MSH6 from 97 subjects negative for mutations in MLH1 and MSH2. Methods: By direct sequencing, we identified 27 MSH6 variants, of which, nine were novel. To verify the pathogenicity of these novel variants we performed in silico and segregation analyses. Results: Three novel variants were predicted by in silico analysis as damaging mutations and segregated with the disease phenotype. While, a novel frameshift deletion variant that was predicted to yield a premature stop codon, did not segregate with the LS phenotype in 3 of 4 cases in the family. Interestingly, another frame-shift variant identified in this study, already described in the literature, also did not segregate with the LS phenotype in 1 of 2 affected subjects in the family. In all affected subjects of both families, no mutation was detected in other MMR genes. Therefore, it is expected that within these families other genetic factors contribute to the disease either alone or in combination with MSH6 variants. Conclusion: We conclude that caution should be exercised in counseling for MSH6-associated LS family members.

Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

Although ladybirds of European Russia and the Caucasus have been the subject of numerous ecological and faunistic investigations, there is an evident lack of appropriate identification key for them. All previous keys have been published in Russian. The most modern key was published more than 50 years ago and included only about 60 % of species. Guides for identification of Coccinellidae of other countries are not appropriate for European Russia, since do not include many species occurring in the regions. New, original key to subfamilies, genera, and species of ladybirds (Coccinellidae) of the European Russia and Russian Caucasus is presented. All native species recorded in the region and all alien species introduced to this region are included. Some species from the adjacent regions are added. In total, 110 species are keyed and illustrated with line drawings. Photographs of rare and endemic species are provided. Information on the distribution of species within the region under consideration is provided. Synonymy of Chilocorus kuwanae with Ch. renipustulatus is presented and discussed.

Many clinical research datasets have a large percentage of missing values that directly impacts their usefulness in yielding high accuracy classifiers when used for training in supervised machine learning. While missing value imputation methods have been shown to work well with smaller percentages of missing values, their ability to impute sparse clinical research data can be problem specific. We previously attempted to learn quantitative guidelines for ordering cardiac magnetic resonance imaging during the evaluation for pediatric cardiomyopathy, but missing data significantly reduced our usable sample size. In this work, we sought to determine if increasing the usable sample size through imputation would allow us to learn better guidelines. We first review several machine learning methods for estimating missing data. Then, we apply four popular methods (mean imputation, decision tree, k-nearest neighbors, and self-organizing maps) to a clinical research dataset of pediatric patients undergoing evaluation for cardiomyopathy. Using Bayesian Rule Learning (BRL) to learn ruleset models, we compared the performance of imputation-augmented models versus unaugmented models. We found that all four imputation-augmented models performed similarly to unaugmented models. While imputation did not improve performance, it did provide evidence for the robustness of our learned models.

Olive trees have been of economic and cultural value since pre-Roman times, and continue to dominate landscapes and agriculture in many mediterranean regions. Recent mass losses of olive trees in Southern Italy due to an exotic plant pathogen highlight the need for methods that to monitor the olive trees in a landscape or region operationally. Here, we develop a method for counting olive trees from aerial photographs and test it in areas with a high diversity of olive tree ages, sizes, and shapes. This heterogeneity complicates tree counting as centennial trees often have crowns that are split into multiple segments, resembling multiple crowns, while nearby crowns often form a semi-closed canopy comprising multiple trees. Comparisons with reference counts in two 20 ha sites and over three different years indicate the automated counts tend to be reasonably accurate (median error 13%, n = 6), but heavily influenced by a few olive orchards with particularly high planting densities and a relatively closed canopy in which distinguishing individual trees is challenging. Overall, the algorithm estimated tree densities well (counting 82 to 109 trees/ha versus 87 to 104 trees/ha in the reference counts), indicating the method is suitable to track the number of olive trees over large areas.

We evaluated the mono- and combination-therapy effects of valproic acid (VPA) and doxorubicin (DOX) in hepatocellular carcinoma (HCC) and identified a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of zinc fingers, and most of all the applications of CRISPR-Cas9 technology, has given researchers new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR, possibly treating more diseases such as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of HIV-1, inhibiting HIV-1 gene expression. Since 2013, several other researchers have blocked HIV replication and infection through CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells, which consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus cannot bind to T-cells, blocking the initial attachment stage, and discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improving the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission or a functional cure.

Nine crossbred finishing barrows randomly assigned to 3 dietary treatments were used to investigate the effects of dietary lysine on muscle growth related metabolic and signaling pathways. Muscle samples were collected from the longissimus dorsi of individual pigs after feeding the lysine-deficient, lysine-adequate, or lysine-excess diet for 5 weeks, and the total RNA was extracted afterwards. Affymetrix Porcine Gene 1.0 ST Array was used to quantify the expression levels of 19,211 genes. A total of 674 transcripts were differentially expressed (P ≤ 0.05); 60 out of 131 transcripts (P ≤ 0.01) were annotated in the NetAffx database. Ingenuity pathway analysis showed that dietary lysine deficiency may lead to (1) increased muscle protein degradation via the ubiquitination pathway as indicated by the up-regulated DNAJA1, HSP90AB1 and UBE2B mRNA, (2) reduced muscle protein synthesis via the up-regulated RND3 and ZIC1 mRNA, (3) increased serine and glycine synthesis via the up-regulated PHGDH and PSPH mRNA, and (4) increased lipid accumulation via the up-regulated ME1, SCD, and CIDEC mRNA. Dietary lysine excess may lead to (1) decreased muscle protein degradation via the down-regulated DNAJA1, HSP90AA1, HSPH1, and UBE2D3 mRNA, and (2) reduced lipid biosynthesis via the down-regulated CFD and ME1 mRNA.

Microorganisms belonging to the Lactobacillus genus are naturally associated or deliberately added to fermented food products and are widely used in probiotic food additives and supplements. Moreover these bacteria normally colonize mouth, gastrointestinal (GI) tract and female genitourinary tract of humans. They exert multiple beneficial effects and are regarded as safe microorganisms. However, infections caused by lactobacilli, mainly endocarditis, bacteremia and pleuropneumonia occasionally occur. The relevance of Lactobacillus spp. as opportunistic pathogens in humans and related risk factors and predisposing conditions are illustrated in this review article with more emphasis on the species L. rhamnosus, that has been more often involved in infection cases. The methods used to identify this species in clinical samples, to distinguish strains and to evaluate traits that can be associated to pathogenicity, as well as future perspectives for improving the identification of potentially pathogenic strains are outlined.

This study inscribes itself in the global discussion about the issue of environmental awareness, beliefs and behaviors. Here we focus on the role that cultural differences and scientific media dieting play in explaining heterogeneities in students' awareness and expectations about the two environmental issues of deforestation and species (plant and animal) extinction in the Middle East and North America. To this end, we use the cross-sectional survey data of the OECD's Program for International Student Assessment (PISA) 2015, along with seemingly unrelated Bi-variate ordered Probit modeling techniques. The results show that compared to their North American Counterparts, students' in the Middle East are 14.2% less aware of, and 14.5% less optimistic about the issue of deforestation, while 38.9% less aware of, and 59.0% less optimistic about the issue of species extinction. In addition, we found that science club attendance and broad science reading in books are the two most effective communication media for raising students awareness about the two environmental issues. In fact, every one level increase in students' awareness is found to raise their optimism by 20.4% for the issue of deforestation, and 15.0% for the issue of plant and animal extinction. Therefore raising young people environmental awareness and optimism through proper communication strategies, could be invaluable for achieving an economic development in line with our need to preserve the natural environment and ecosystem services for generations to come.

The eastern subterranean termite, Reticulitermes flavipes, currently inhabits previously glaciated regions of the northeastern U.S., as well as the unglaciated southern Appalachian Mountains and surrounding areas. We hypothesized that Pleistocene climatic fluctuations have influenced the distribution of R. flavipes, and thus the evolutionary history of the species. We estimated contemporary and historical geographic distributions of R. flavipes by constructing Species Distribution Models (SDM). We also inferred the evolutionary and demographic history of the species using mitochondrial (cytochrome oxidase I and II) and nuclear (endo-beta-1,4-glucanase) DNA sequence data. To do this, genetic populations were delineated using Bayesian spatial genetic clustering, competing hypotheses about population divergence were assessed using approximate Bayesian computation (ABC), and changes in population size were estimated using Bayesian skyline plots. SDMs identified areas in the north with suitable habitat during the transition from the Last Interglacial to the Last Glacial Maximum, as well as an expanding distribution from the mid-Holocene to the present. Genetic analyses identified three geographically cohesive populations, corresponding with northern, central, and southern portions of the study region. Based on ABC analyses, divergence between the Northern and Southern populations was the oldest, estimated to have occurred 64.80 thousand years ago (kya), which corresponds with the timing of available habitat in the north. The Central and Northern populations diverged in the mid-Holocene, 8.63 kya, after which the Central population continued to expand. Accordingly, phylogeographic patterns of R. flavipes in the southern Appalachians appear to have been strongly influenced by glacial-interglacial climate change.

The origin of life has not been solved as yet, in spit of the time passage more than thirty years from publication of RNA world hypothesis by W. Gilbert (1986), which is based on the “gene/replicator--first” theory. On the contrary, I have proposed [GADV]-protein world hypothesis (GADV hypothesis), assuming that life emerged from [GADV]-protein world, which is grounded on the “protein/metabolism-first” theory. However, two weak points of protein world hypothesis, (i) protein cannot be produced without gene, and (ii) protein cannot be self-replicated, have been frequently pointed out by supporters of RNA world hypothesis. Then, I examined whether the two weak points could be overcome by GADV hypothesis or not. From the results, it was confirmed that (i) [GADV]-protein could be pseudo-replicated in the absence of gene owing to protein 0^th-order structure or [GADV]-amino acids, and (ii) the replication ability is not always required from the beginning but it is sufficient to acquire it at some time point until the emergence of life. Thus, it was concluded that life emerged as [GADV]-protein world hypothesis, which is grounded on the “protein/metabolism-first” theory, expects.

Questions: Elevation, biodiversity, and forest structure are commonly correlated, but their relationships near the positive extremes of biodiversity and elevation are unclear. We asked 1) How does forest structure vary with elevation in a high biodiversity, high topographic complexity region? 2) Does forest structure predict vascular plant biodiversity? 3) Is plant biodiversity more strongly related to elevation or to forest structure? Location: Great Smoky Mountains National Park, USAMethods: We used terrestrial LiDAR scanning (TLS) to characterize vegetation structure in 12 forest plots. We combined two new canopy structural complexity metrics with traditional TLS-derived forest structural metrics and vascular plant biodiversity data to investigate correlations among forest structure metrics, biodiversity, and elevation. Results: Forest structure varied widely across plots spanning the elevational range of GRSM. Our new measures of canopy density (Depth) and structural complexity (σDepth) were sensitive to structural variations and effectively summarized horizontal and vertical dimensions of structural complexity. Vascular plant biodiversity was negatively correlated with elevation, and more strongly positively correlated with vegetation structure variables. Conclusions: The strong correlations we observed between canopy structural complexity and biodiversity suggest that structural complexity metrics could be used to assay plant biodiversity over large areas in concert with airborne and spaceborne platforms.

Knowledge-based approaches are useful alternatives to predict the Failure Probability (FP) coping with the insufficient data, process integrity, and complexity issue in manufacturing systems. This study proposes a Fault Tree Analysis (FTA) approach as proactive knowledge-based technique to estimate the FP based maintenance planning with subjective information from domain experts. However, the classical-FTA still suffers from uncertainty and static structure limitations which poses a substantial dilemma in predicting FP. To deal with the uncertainty issues, a Fuzzy-FTA (FFTA) model was developed by statistical analysing the effective attributes such as experts' trait impacts, scales variation and, assorted membership and defuzzification functions. Besides, a Bayesian Network (BN) theory was conducted to overcome the static limitation of classical-FTA. The results of FFTA model revealed that the changes in decision attributes were not statistically significant on FP variation while BN model considering conditional rules to reflect the dynamic relationship between events had more impact on predicting FP. After all, the integrated FFTA-BN model was used in the optimization model to find the optimal maintenance intervals according to estimated FP and the total expected cost. As a practical example, the proposed model was implemented in a semi-automatic filling system in an automotive production line. The outcomes could be useful for upgrading the availability and safety of complex equipment in manufacturing systems.

There have been a great number of investigations about the influence of weak magnetic fields on biological systems, such as isolated cells and whole organisms. This is also a subject of considerable medical concern since old epidemiologic observations have indicated a possible tumorigenic effect of these fields. Their mechanism of action, however, is not firmly established. A large number of biological effects of electromagnetic fields have been attributed either to the production of reactive oxygen species (ROS) or to the entrance Ca²⁺ in the cell. A new biochemical pathway is proposed that covers these two possibilities: the primary effect of the magnetic field would be by the mechanism of radical pairs resulting in the production of ROS; these could activate the ion channels TRPM2 producing cellular inflow of Ca²⁺, which would induce the calcium dependent effects. Thus, a large number of biological effects observed up to the present could be explained.

Today massive amounts of sequenced metagenomic and -transcriptomic data from different ecological niches and environmental locations are available. Scientific progress depends critically on methods that allow extracting useful information from the various types of sequence data. Here, we will first discuss types of information contained in the various flavours of biological sequence data, and how this information can be interpreted to increase our scientific knowledge and understanding. We argue that a mechanistic understanding is required to consistently interpret experimental observations, and that this understanding is greatly facilitated by the generation and analysis of dynamic mathematical models. We conclude that, in order to construct mathematical models and to test mechanistic hypotheses, time-series data is of critical importance. We review diverse techniques to analyse time-series data and discuss various approaches by which time-series of biological sequence data was successfully used to derive and test mechanistic hypotheses. Analysing the bottlenecks of current strategies in the extraction of knowledge and understanding from data, we conclude that combined experimental and theoretical efforts should be implemented as early as possible during the planning phase of individual experiments and scientific research projects.

A construction for the systems of natural and real numbers is presented in Zermelo-Fraenkel Set Thoery, that allows for simple proofs of the properties of these systems, and practical and mathematical applications. A practical application is discussed, in the form of a Simple and Linear Fast Adder (Patent Pending). Applications to finite group theory and analysis are also presented. A method is illustrated for finding the automorphisms of any finite group $G$, which consists of defining a canonical block form for finite groups. Examples are given, to illustrate the procedure for finding all groups of $n$ elements along with their automorphisms. The canonical block form of the symmetry group $\Delta_4$ is provided along with its automorphisms. The construction of natural numbers is naturally generalized to provide a simple and sound construction of the continuum with order and addition properties, and where a real number is an infinite set of natural numbers. A basic outline of analysis is proposed with a fast derivative algorithm. Under this representation, a countable sequence of real numbers is represented by a single real number. Furthermore, an infinite $\infty\times\infty$ real-valued matrix is represented with a single real number. A real function is represented by a set of real numbers, and a countable sequence of real functions is also represented by a set of real numbers. In general, mathematical objects can be represented using the smallest possible data type and these representations are calculable. In the last section, mathematical objects of all types are well assigned to tree structures in a proposed type hierarchy.

Aedes aegypti mosquito is a vector that could transmit various pathogens, such as viruses, bacteria, and parasites. Several human diseases transmitted by Ae. aegypti mosquito are dengue fever (DHF), Chikungunya, Yellow Fever and Zika. The occurance of resistance to various insecticides, including pyrethroid, is a current problem faced by various countries. In this research, a WHO bioassay test on Palembang and Jakarta Ae. aegypti was conducted using 0.25% permethrin pyrethroid insecticide. VGSC gene fragments associated with pyrethroid resistance (L982, S989, I1011, L1014, V1016 and F1534) of resistant and sensitive strains were amplified and analyzed. The test showed the presence of resistance in Ae. aegypti isolates from Palembang and Jakarta. From the results of VGSC gene fragment analyses, it was known that there were mutations (S989P and/or V1016G) on isolates from Palembang and (S989P and/or V1016G) on resistant isolates from Jakarta.

Oxidative and nitrosative stress are a common problem when manipulating gametes in vitro. In vitro development in mammalian embryos is highly affected by culture conditions, especially by reactive oxygen species (ROS) and reactive nitrogen species (RNS), because its absence or over production causes embryo arrest and changes in gene expression. Melatonin in gamete co-incubation during IVF has deleterious or positive effects depending on the concentration used in culture medium, demonstrating the delicate balance that must exist between antioxidant and pro-oxidant activity. Further research is needed to better understand the possible impact of melatonin on the different IVP steps in domestic animals, especially in seasonal breeds where this neuro-hormone system highly regulates its reproduction physiology.

In the wake of the current SARS-CoV-2 pandemic devastating the world, it is imperative to elucidate the comparative genomics of geographically-diverse strains of this novel coronavirus to gain insights into its microevolution, pathogenesis and control. Here we explore the molecular nature, genome-wide frequency, and gene-wise distribution of mutations in three distinct datasets encompassing 68 SARS-CoV-2 RNA-genomes altogether. While phylogenomic analysis revealed parallelism between the evolutionary paths charted by distinct quasispecies clusters of the virus, occurrence of mutations across genomes was found to be non-random. Whereas deletion mutations are extremely scarce and insertions totally absent, of all the instances of single nucleotide substitution detected, the overwhelming majority were transition mutations with cytidine to uridine being the most prevalent type. Propensity of this transition could be attributed to hydrolytic deamination mediated by ultra-violet irradiation or bisulfite reagent, both of which find wide usage as sterilizer/disinfectant. Transversions, albeit few and predominated by the guanosine to uridine form, were found concentrated in loci encoding the structural proteins of the virus, so might confer versatile tissue-colonization potentials. Mutation frequency of the three distinct genome-sets ranged narrowly between 0.07-1.08 × 10^-4 nucleotides positions mutated per nucleotide aligned. Gene-wise mapping of the global mutations illuminated the highly conserved nature of the genes encoding the non-structural proteins Nsp7, Nsp8 (two essential cofactors of the viral RNA-dependent RNA-polymerase) and Nsp9 (Nsp8-interacting single-strand RNA-binding protein), plus the envelope protein E (involved in SARS-CoV-2 assembly, budding and pathogenesis). These mutation-free genomic loci and/or their protein products could be potent targets for future drug designing/targeting.

Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical system theory represents a high-dimensional cell state space, in which each cell phenotype is considered as an “attractor” that is determined by interactions among multiple variables (molecular players), and is buffered against environmental fluctuations. Further, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss these phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of “cancer attractors” – hidden stable states of the underlying regulatory network that are not occupied by normal cells. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of drug/hormone resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to drug/hormone treatment. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes ‘recanalization’, i.e. the exit from “cancer attractors” and re-entry into “normal attractors”, is more likely to succeed rather than a conventional approach that targets individual molecules/pathways.

Although current antiretroviral drug therapy can suppress human immunodeficiency virus (HIV) replication, a lifelong prescription is necessary to avoid viral rebound. The problem of persistent and ineradicable viral reservoirs in HIV-infected people continues to be a global threat. In addition, some HIV-infected patients do not experience sufficient T-cell immune restoration despite being aviremic during treatment, and this is likely due to altered hematopoietic potential. To achieve global eradication of HIV disease, a cure is needed. To this end, tremendous efforts have been made in the field of anti-HIV gene therapy. This review will discuss the concepts of HIV cure and relative viral attenuation and provide an overview of various gene therapy approaches aimed at a complete or functional HIV cure and protection of hematopoietic functions.

Bent trees have been observed during the early years in juvenile plantations (less than 5 years-old) of Tectona grandis in Costa Rica. The relationship between bending and the morphological characteristics of the trees was explored. An evaluation of bent trees was conducted in six juvenile plantations (8, 17, 27, 28, 31, and 54 months old) of Tectona grandis. Site 1 with 8-month-old plantations did not display any relationship with any tree morphological variable (diameter, height, and crown weight of tree), whereas for the sites 2, 3, and 4 with 17-, 27-, and 28-month-old plantations, respectively, all the tree morphological variables were statistically correlated with the bent trees. A multiple regression analysis showed that the most influential variables were height to crown base, crown weight, diameter, and total height of the tree. An evaluation of the bending risk factor (RF) was correlated with the height to crown base, crown weight, and form factor. The modulus of elasticity and chemical compositions of bent trees differed from those of straight trees. The causes of tree bending are complex, involving, among other factors, the morphology of the trees, plantation conditions, and other factors specific to the xylem, such as the specific gravity, modulus of elasticity, and presence of calcium and magnesium in the wood.

The comprehensibility of good predictive models learned from high-dimensional gene expression data is attractive because it can lead to biomarker discovery. Several good classifiers provide comparable predictive performance but differ in their abilities to summarize the observed data. We extend a Bayesian Rule Learning (BRL-GSS) algorithm, previously shown to be a significantly better predictor than other classical approaches in this domain. It searches a space of Bayesian networks using a decision tree representation of its parameters with global constraints, and infers a set of IF-THEN rules. The number of parameters and therefore the number of rules are combinatorial to the number of predictor variables in the model. We relax these global constraints to a more generalizable local structure (BRL-LSS). BRL-LSS entails more parsimonious set of rules because it does not have to generate all combinatorial rules. The search space of local structures is much richer than the space of global structures. We design the BRL-LSS with the same worst-case time-complexity as BRL-GSS while exploring a richer and more complex model space. We measure predictive performance using Area Under the ROC curve (AUC) and Accuracy. We measure model parsimony performance by noting the average number of rules and variables needed to describe the observed data. We evaluate the predictive and parsimony performance of BRL-GSS, BRL-LSS and the state-of-the-art C4.5 decision tree algorithm, across 10-fold cross-validation using ten microarray gene-expression diagnostic datasets. In these experiments, we observe that BRL-LSS is similar to BRL-GSS in terms of predictive performance, while generating a much more parsimonious set of rules to explain the same observed data. BRL-LSS also needs fewer variables than C4.5 to explain the data with similar predictive performance. We also conduct a feasibility study to demonstrate the general applicability of our BRL methods on the newer RNA sequencing gene-expression data.

The scene for regional biogeography and human settlements in Central Amazonia is set by the river network, which presumably consolidated in the Pliocene. However, we present geomorphological and sediment chronological data showing that the river network has been anything but stable. Even during the last 50 kyr, the tributary relationships have repeatedly changed for four major rivers, together corresponding to one third of the discharge of the Amazon. The latest major river capture event converted the Japurá from a tributary of the Rio Negro to a tributary of the Amazon only 1000 years ago. Such broad-scale lability implies that rivers cannot have been as efficient biogeographical dispersal barriers as has generally been assumed, but that their effects on human societies can have been even more profound. Climate change and deforestation scenarios predict increasing water levels during peak floods, which will likely increase the risk of future river avulsions. This may have disastrous consequences for the local human societies, especially in those areas where the current floodplains are at only marginally lower elevations than the nearest water divide. We suggest that the prevailing paradigm of rivers as principal structuring elements of Amazonian biogeography needs to be re-evaluated, and that land use planning and civil risk assessment should take the possibility of river avulsions into account.

Bacteria currently included in Rhizobium leguminosarum are too diverse to be considered a single species, so we can refer to this as a species complex (the Rlc). We have found 429 publicly available genome sequences that fall within the Rlc and these show that the Rlc is a distinct entity, well separated from other species in the genus. Its sister taxon is R. anhuiense. We constructed a phylogeny based on concatenated sequences of 120 universal (core) genes, and calculated pairwise average nucleotide identity (ANI) between all genomes. From these analyses, we concluded that the Rlc includes 18 distinct genospecies, plus 7 unique strains that are not placed in these genospecies. Each genospecies is separated by a distinct gap in ANI values, usually at around 96% ANI, implying that it is a 'natural' unit. Five of the genospecies include the type strains of named species: R. laguerreae, R. sophorae, R. ruizarguesonis, "R. indicum" and R. leguminosarum itself. The 16S ribosomal RNA sequence is remarkably diverse within the Rlc, but does not distinguish the genospecies. Partial sequences of housekeeping genes, which have frequently been used to characterise isolate collections, can mostly be assigned unambiguously to a genospecies, but alleles within a genospecies do not always form a clade, so single genes are not a reliable guide to the true phylogeny of the strains. We conclude that access to a large number of genome sequences is a powerful tool for characterising the diversity of bacteria, and that taxonomic conclusions should be based on all available genome sequences, not just those of type strains.

Proper and timely segregation of cellular genome is an important and a prime requirement of all cell division programmes. Mis-segregation of chromosomes and resulting aneuploidy leads to several clinical consequences. Over the years, shugoshin emerges as a key protein factor involved in the segregation of genetic material in dividing cells. Deletion or altered level of shugoshin is reported in several human malignancies, as a result, shugoshin now emerges as an important tumour associated gene and a possible target for cancer therapy. Apart from the role in cancer, recent studies also showed the involvement of shugoshin in several other clinical disorders. Through this review, we tried to highlight the clinical relevance of shugoshin.

In both managed and unmanaged forests, termites are functionally important members of the dead-wood-associated (saproxylic) insect community. However, little is known about regional-scale environmental drivers of geographic distributions of termite species, and how these environmental factors impact co-occurrence among congeneric species. Here we focus on the southern Appalachian Mountains—a well-known center of endemism for forest biota—and use Ecological Niche Modeling (ENM) to examine the distributions of three species of Reticulitermes termites (i.e., R. flavipes, R. virginicus, and R. malletei). To overcome deficiencies in public databases, ENMs were underpinned by field-collected high-resolution occurrence records coupled with molecular taxonomic species identification. Spatial overlap among areas of predicted occurrence of each species was mapped, and aspects of niche similarity were quantified. We also identified environmental factors that most strongly contribute to among-species differences in occupancy. Overall, we found that R. flavipes and R. virginicus showed significant niche divergence, which was primarily driven by dry-season precipitation. Also, all three species were most likely to co-occur in the mid-latitudes of the study area (i.e., northern Alabama and Georgia, eastern Tennessee and western North Carolina), which is an area of considerable topographic complexity. This work provides important baseline information for follow-up studies of local-scale drivers of these species’ distributions. It also identifies specific geographic areas where future assessments of the frequency of true syntopy vs. micro-allopatry, and associated interspecific competitive interactions, should be focused.

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the ApoE gene and plasmatic apolipoprotein E (ApoE) levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: 100 participants were included (71% women, average age, 70 yrs., range 43-91). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Multivariate logistic regression models adjusted by age and gender were performed to examine the risk association of MCI with plasma ApoE and APOE methylation Results: MCI was diagnosed in 41 subjects (average age, 66.5±9.6 yrs.) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (P<0.05). Higher CpG-227 methylation correlated with lower risk for MCI (P=0.002). Only CpG-227 was significantly correlated with plasmatic ApoE levels (correlation coefficient=-0.665; P=0.008). Conclusion: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns can be used as potential biomarkers to identify early stages of MCI.

Thalassemia is genetic blood disease cause by absence or decrease of one or more of the globin chain synthesis. Beta thalassemia is characterized by one or more mutations in beta globin gene. Absence or reduced amount the of beta globin chains cause ineffective erythropoiesis which leads to anemia. Beta thalassemia has been further divided into three main forms: Thalassemia minor/silent carrier, major and intermedia. More severe form is thalassemia major in which patients depend upon blood transfusion for survival and high level of iron occur as a consequence of consistent blood transfusion. Over loaded iron invokes the synthesis of reactive oxygen species that are toxic in redundancy and triggering the impairment to vascular, endocrine and hepatic system. Thalassemia can be diagnosed and detected through various laboratory tests such as blood smear, prenatal testing (genetic testing of amniotic fluid), DNA analysis (genetic testing) and complete blood count. Treatment of thalassemia intermedia is symptomatic but it can also be managed by splenectomy and folic supplementation. While thalassemia major can be treated by transplantation of bone marrow, regular transfusion of blood and iron chelation treatment, stimulation of fetal hemoglobin production, hematopoietic stem cell transplantation and gene therapy.

Macrobrachium rosenbergii is a valuable freshwater prawn in Asian aquaculture. In recent years, a new symptom that was generally called as ‘white head’ caused high mortality in M. rosenbergii farms in China. Samples of M. rosenbergii, M. nipponense, Procambarus clarkii, M. superbum, Penaeus vannamei, and Cladocera from a farm suffering from ‘white head’ in Jiangsu Province were collected and analyzed in this study. Pathogen detection showed that all samples were positive for Shrimp hemocyte iridescent virus (SHIV). Histopathological examination revealed dark eosinophilic inclusions and pyknosis in hematopoietic tissue, hepatopancreas and gills of M. rosenbergii and M. nipponense. Blue signals of in situ DIG-labeled LAMP (ISDL) appeared in hematopoietic tissue, hemocytes, hepatopancreatic sinus, and antennal gland. TEM of ultrathin sections showed a large number of SHIV particles with a mean diameter about 157.9 nm. The virogenic stromata and budding virions were observed in hematopoietic cells. Quantitative detection by TaqMan probe based real-time PCR of different tissues in natural infected M. rosenbergii showed that hematopoietic tissue contained the highest SHIV load with a relative abundance of (25.4±16.9)%. Hepatopancreas and muscle contained the lowest SHIV load with a relative abundance at (2.44±1.24)% and (2.44±2.16)%, respectively. Above results verified that SHIV is the pathogen causing ‘white head’ in M. rosenbergii, and M. nipponense and Pr. clarkii are also the susceptible species of SHIV.

Selenocyanates form an interesting class of organic selenium compounds as they serve as multifunctional agents (being the precursors of seleninic acids and diselenides in synthetic chemistry and as antimicrobial and cytotoxic agent in biology) and, due to their similarity with better known thiocyanates promise high biological activity. Yet whilst selenocyanates are common in synthetic chemistry, they are rarely considered in pharmaceutical design. Arylmethyl selenocyanates (1-13) have been synthesized and an insight into their structural properties using X-ray crystallography has been obtained. The compounds subsequently have been evaluated for their potential antimicrobial, nematicidal and cytotoxic activity. ADMET properties in vitro, using mutagenicity (AMES) and permeability (PAMPA) tests, have been determined. The compounds exhibit pronounced activity against various strains of bacteria (both Gram-positive and Gram-negative) and yeasts. Among them, benzylselenocyanate (1) represents the most active anti-ESKAPE agent, with potent antibacterial activity, especially against multidrug resistant MRSA strains (HEMSA 5). Our results demonstrate that the arylmethyl selenocyantes are not only non-mutagenic but also possess moderate cytotoxic activity against cancer cells.

Urban forests are critical infrastructure for mitigating environmental and social challenges cities face. Municipalities and non-governmental entities, among others, often set goals (e.g., tree planting or canopy targets) to support urban forests and their benefits. We focus on canopy goals and develop conceptual underpinnings for an analysis of where additional canopy, as one important dimension of the urban forest, can fit within the landscape, while considering factors that influence where trees can be planted and where canopy can grow – ‘practical canopy.’ We apply this in New York City (NYC) to inform the setting of a canopy goal by the NYC Urban Forest Task Force (UFTF) for the NYC Urban Forest Agenda, which may trigger a virtuous cycle that supports the urban forest there. We further develop framing for a ‘priority canopy’ analysis to understand where urban forest expansion should be prioritized given more context (e.g., environmental hazards, local preferences), which can inform how expansion of the urban forest is achieved. We estimate an opportunity for 15,899 ha of new canopy in NYC given existing opportunities and constraints (practical canopy), which, if leveraged, could result in nearly doubling the canopy as of 2017 (17,253 ha). However, like existing canopy, practical canopy is not evenly distributed, in general, or across jurisdictions and land uses. Relying solely on areas identified as practical canopy to expand the urban forest would exacerbate inequities in its distribution. We discuss how the NYC UFTF established an aspirational but achievable goal of 30% canopy cover by 2035, which was informed by this analysis and guided by priorities of equity, health, and resilience. Achievement of this goal will ultimately require a combination of protecting and stewarding the existing resource, and leveraging opportunities for tree planting. Achieving a more equitable urban forest will also require identification of priority canopy, and, in cases, creation of new opportunities for tree planting and canopy expansion. Overall, the collaborative establishment of such goals based on local context can be instrumental in creating a virtuous cycle, moving conservation actors toward exercising influence and agency within the social ecological system.

Cystic Fibrosis is a rare genetic disease that affects the transmission of chloride ions due to mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Even though there are nearly 2000 mutations identified to be related to the condition, the most common mutation is F508del; deletion of a phenylalanine residue at 508. On the other hand, G542X which is a Class I mutation is also found very commonly and there are no modulator treatments available for it. Furthermore, it was investigated that R553X mutation can as well be corrected simultaneously with G542X mutation. Therefore, the main focus is on designing a gene therapy project that can correct all these three mutations at once by utilizing the prime editing technique via lipid-based delivery. In this way, the mutations can be edited through plasmids that were designed containing 2 pegRNAs and the Cas enzyme. To implement such an approach efficiently, both ex vivo, an animal model, and in vivo steps are to be designed. For the cell line, fibroblasts are selected due to their simplicity and low cost. The animal model of the experiment is determined to be a ferret concerning the high similarity to the human's CFTR protein and finally, the procedure will follow on a direct application in human Cystic Fibrosis patients. The plasmids are thought to be delivered through a cationic liposome that will reach the lungs with the aid of a nebulizer. At the last stage of the experimental procedure, Sanger Sequencing will be done to see if the desired edit within the CFTR has been performed successfully, and Next Generation Sequencing will be executed to see if there has been an off-target mutation in the remainder of the genome. Whereas for detecting the presence and expression of CFTR protein in humans, immunodetection with flow cytometry will be conducted.

Horizontal gene transfer (HGT) is the transmission of genes between organisms by other means than parental to offspring inheritance. While it is prevalent in prokaryotes, HGT is less frequent in eukaryotes and particularly in metazoan. Here, we propose Alienness, a taxonomy-aware web application that parses BLAST results against public libraries to rapidly identify candidate HGT in any genome of interest. Alienness takes as input the result of a BLAST of a whole proteome of interest against any NCBI protein library. The user defines recipient (e.g. metazoan) and donor (e.g. bacteria, fungi) branches of interest in the NCBI taxonomy. Based on the best BLAST E-values of candidate donor and recipient taxa, Alienness calculates an Alien Index (AI) for each query protein. An AI >0 indicates a better hit to candidate donor than recipient taxa and a possible HGT. Higher AI represent higher gap of E-values between candidate donor and recipient and a more likely HGT. We confirmed the accuracy of Alienness on phylogenetically confirmed HGT of non-metazoan origin in plant-parasitic nematodes. Alienness scans whole proteomes to rapidly identify possible HGT in any species of interest and thus fosters exploration of HGT more easily and largely across the tree of life.

Rice grassy stunt virus (RGSV) a member of Tenuivirus family, is very potent and destructive which effects rice crop in many countries, particularly China. Non coding RNAs have important functions in development and epigenetic regulation of gene expression in numerous organsisms. There is three type of small non coding RNAs have been found in eukaryotes, which are small interferring RNAs (siRNAs), microRNAs (miRNAs) and piwi interacting RNAs (piRNAs). Small RNAs (sRNAs) origination is from the infecting virus which is known as virus-derived small interfering RNAs (vsiRNAs), has responsibility for RNA silencing in plants. Virus-induced gene silencing (VIGS) is mainly dependent on RNA silencing (RNAi). Interestingly, RNA silencing happens in plants during viral infections. RNAi technique showed significant results in Nephotettix cincticeps. RNAi technique demonstrated the gene silencing of planthopper Nilaparvata lugens. The proteins P5, pcf4, Dnj, psn5, and pn6 act as potential movement proteins and serve as silencing suppressors for RGSV. VsiRNAs originate from dsRNA molecules which require Dicer-like (DCL) proteins, RNA dependent RNA polymerase (RdRP) proteins, and Argonaute (AGO) proteins. RdRP uses ssRNA for perfect RNA amplification process and can also be used for DCL dependent secondary vsiRNA formation. VSRs interfere with the movement of signals during silencing mechanism. Moreover, intercellular movement of viruses is facilitated by virus-encoded movement protein. RNAi is found in many eukaryotes which are related to transcriptional or post-transcriptional regulation by gene suppression. Transcription is bidirectional in ssDNA viruses which are originated from dsRNA molecules. In this review, we highlighted the biology of Rice grassy stunt virus and its insect vector and its silencing suppressors. This work will be helpful for plant virologists to understand the whole biogenesis mechanism for rice viruses especially RGSV.

Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and anti-inflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

Faba bean (Vicia faba L.), a member of the Fabaceae family, is one of the important food legumes cultivated in cool temperate regions. It holds great importance for human consumption and livestock feed because of its high protein content, dietary fibre, and nutritional value. Major faba bean breeding challenges include its mixed breeding system, unknown wild progenitor, and genome size of ~13 Gb, which is the largest among diploid field crops. The key breeding objectives in faba bean include improved resistance to biotic and abiotic stress and enhanced seed quality traits. Major progress on reduction of vicine-convicine and seed coat tannins, the main anti-nutritional factors limiting faba bean seed usage, have been recently achieved through gene discovery. Genomic resources are relatively less advanced compared to other grain legume species, but significant improvements are underway due to a recent significant increase in research activities. A number of bi-parental populations have been constructed and mapped for targeted traits in the last decade. Faba bean now benefits from saturated synteny‐based genetic maps, along with next-generation sequencing and high-throughput genotyping technologies that are paving the way for marker-assisted selection. Developing a reference genome, and ultimately a pan-genome, will provide a foundational resource for molecular breeding. In this review, we cover the recent development and deployment of genomic tools for faba bean breeding.

Researchers in different disciplines studied liver’s genetic expression of organogenesis in embryogenesis; however, organogenesis has not been studied as an independent and a complementary process during adult liver regeneration. This paper reviewed studies and extracted information related to organogenesis in adult liver regeneration because of organogenesis’ important role in cancer and tissue regeneration.

The alien invasive insect pest Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), commonly referred to as Fall Armyworm (FAW), is a polyphagous insect feeding on more than 350 host plants in addition to maize in its native habitat. Due to the voracious nature of FAW, significant yield losses on maize production were reported across the African continent since its detection in 2016. Despite being a polyphagous insect, little is known about its alternative host plants in the new habitat including Mozambique. This study aimed to assess the host range of FAW in the central province of Manica, Mozambique. A field survey was conducted from May to August 2019 (dry season of 2018/2019 cropping season) and in December 2019 and January 2020 (rainy season of 2019/2020 cropping season) in maize fields and crops often mixed with maize or located in the vicinity of maize fields. A total of 1291 fields were surveyed. In each field, 20 plants were selected in a “W” pattern and checked for the presence of FAW egg masses and/or larvae. At the time of the sampling, no evidence was found suggesting that in Manica province FAW feeds in crops other than maize because out of 35 different crops surveyed, FAW was only recorded on maize. Results from this study suggest that the strain of FAW occurring in Manica province might be the one specialized in maize or the continuous availability of maize fields throughout the year is influencing the choices of the host plants of this invasive insect pest.

Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. The effect of current chemotherapy regimens against cholangiocarcinoma is limited, and the prognosis of patients with cholangiocarcinoma is poor. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability during carcinogenesis. Studies have shown that the tumor suppressor genes and microRNAs (miRNAs) including MLH1, p14, p16, DAPK, miR-370 and miR-376c are frequently methylated in cholangiocarcinoma. Silencing of these tumor suppressor genes and miRNAs plays critical roles in the initiation and progression of cholangiocarcinoma. In addition, recent studies have demonstrated that DNA methylation inhibitors induce expression of endogenous retroviruses and exert the anti-tumor effect of via an anti-viral immune response. Aberrant DNA methylation of tumor suppressor genes and miRNAs could be a powerful biomarker for diagnosis and treatment of cholangiocarcinoma. Epigenetic therapy with DNA methylation inhibitors hold considerable promise for the treatment of cholangiocarcinoma through re-activation of tumor suppressor genes and miRNAs as well as induction of an anti-viral immune response.

During speciation-with-gene-flow, a transition from single-locus to multi-locus processes can occur, as strong coupling of multiple loci creates a barrier to gene flow. Testing predictions about such transitions with empirical data requires building upon past theoretical work and the continued development of quantitative approaches. We simulated genomes under different evolutionary scenarios of gene flow and divergent selection, extending previous work with the additions of neutral sites and coupling statistics, allowing us to investigate if and how selected and neutral sites differ in the conditions they require for transitions during speciation. As the per-locus strength of selection grew and/or migration decreased, it became easier for selected sites to show divergence – and thus to rise in linkage disequilibrium (LD) with each other as a statistical consequence – farther in advance of the conditions under which neutral sites could diverge. Indeed, even very low rates of gene flow were sufficient to prevent differentiation at neutral sites. However, once strong enough, coupling among selected sites eventually reduced gene flow at neutral sites as well. To explore whether similar transitions might be detectable in empirical data, we used published genome resequencing data from three taxa of Heliconius butterflies. We found that allele-frequency outliers and F ST outliers exhibited stronger patterns of LD than the genomic background, as expected. The statistical characteristics of LD – likely indicative of the strength of coupling of barrier loci – varied between chromosomes and taxonomic comparisons. Broad qualitative agreement between the patterns we observed in the empirical data and our simulations suggests that selection drives rapid genome-wide transitions to multi-locus coupling, illustrating how divergence and gene flow interact along the speciation continuum.

Cellular oxidation is responsive to external and internal stimulation and is generated via signal molecules in defense mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Oxidative stress is not necessarily harmful per se; it depends on the balance between oxidation and antioxidation cascades, which are induced according to stimuli and can maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and ROS production, using IV as an example. We introduce the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS production and various effects of IV infection. We also summarize the potential anti-IV agents that act by targeting oxidative stress.

Tree-killing bark beetles are the most economically important insects in conifer forests worldwide. Yet despite >200 years of research, the drivers of population eruptions or crashes are still not fully understood, precluding reliable predictions of the effects of global change on beetle population dynamics and impacts on ecosystems and humans. We critically analyze potential biotic and abiotic drivers of population dynamics of the European spruce bark beetle (Ips typographus) and present a novel ecological framework that integrates the multiple drivers governing this bark beetle system. We call for large-scale collaborative research efforts to improve our understanding of the population dynamics of this important pest; an approach that might serve as a blueprint for other eruptive forest insects.

Transposable elements (TEs), also known as mobile elements (MEs), are interspersed repeats that constitute a major fraction of the genomes of higher organisms. As one of their important functional impacts on gene function and genome evolution, TEs participate in regulating the expression of genes nearby and even far away at transcriptional and post-transcriptional levels. There are two known principal ways by which TEs regulate expression of genes. First, TEs provide cis-regulatory sequences in the genome with their intrinsic regulatory properties for their own expression making them potential factors for regulating the expression of the host genes. TE-derived cis-regulatory sites are found in promoter and enhancer elements, providing binding sites for a wide range of trans-acting factors. Second, TEs encode for regulatory RNAs with their sequences showed to be present in a substantial fraction of miRNAs and long non-coding RNAs (lncRNAs), indicating the TE origin of these RNAs. Furthermore, TEs sequences were found to be critical for regulatory functions of these RNAs including binding to the target mRNA. TEs thus provide crucial regulatory roles by being part of cis-regulatory and regulatory RNA sequences. Moreover, both TE-derived cis-regulatory sequences and TE-derived regulatory RNAs, have been implicated to provide evolutionary novelty to gene regulation. These TE-derived regulatory mechanisms also tend to function in tissue-specific fashion. In this review, we aim to comprehensively cover the studies regarding these two aspects of TE-mediated gene regulation, mainly focusing on the mechanisms, contribution of different types of TEs, differential roles among tissue types, and lineage specificity, based on data mostly in humans.

Molecular classifications of colorectal cancer (CRC) are benefitting cancer research by providing insights into subtype-specific disease prognosis and better therapeutic intervention. So far different conventional DNA markers such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), chromosomal instability (CIN), and BRAF and KRAS mutations have been used to classify CRC patients but have not shown promising prognostic values. Here, for the first time, we show classification of CRC tumors from Saudi Arabian patients based on gene expression profile (GEP). An existing method of CRC subtyping has been applied to the GEP of tumors from Saudi CRC patients. Survival analysis was carried out on predicted CRC subtypes. In-silico functional analyses were conducted on the gene signature used for subtype prediction. The predicted subtypes showed distinct but statistically insignificant overall survival distribution (log-rank test, p = 0.069). Comparison of predicted subtypes in Saudi CRC patients with that of the French one showed significant dissimilarity in the two populations (Chi-square test, p = 0.0091). Functional analyses of the gene signature used for subtyping suggest their association with “cancer” and “gastrointestinal diseases”. Most of the signature genes were found differentially expressed in CRC tumors compared to adjacent normal tissues. Such a classification framework might help improve the treatment of colorectal cancer patients.

In the present work we present a methodology for teaching the basis of the genetic code through music composition, with the aim to combine science and arts learning. The project was carried out by 155 students, the so-called MARGA Consortium, with ages comprised between 10 and 17 years from different public schools located in the Principality of Asturias, Spain. The different groups generated 8 different music works using a short genetic sequence obtained from the human notch1 gene, receptor of mutations leading to chronic lymphocytic leukemia.

Local cryotherapy is widely used as a treatment for sports-related skeletal muscle injury. However, its molecular mechanisms are unknown. To clarify these mechanisms, in this study, we applied one to three 15-min cold stimulations at 4 °C to various cell lines (in vitro), the tibialis anterior (TA) muscle (ex vivo), and mouse limbs (in vivo). In the in vitro assay, cAMP response element-binding protein 1 (CREB1) was markedly phosphorylated (as pCREB1) and CREB-binding protein (CBP) was recruited to pCREB-1 in response to two or three cold stimulations. In a reporter assay with the cAMP-responsive element, the signals significantly increased after two to three cold stimulations at 4 °C. In the ex vivo study, CREB-targeting genes were significantly upregulated following two or three cold stimulations. The in vivo experiment disclosed that cold stimulation of a mouse limb for 9 days significantly increased mitochondrial DNA copy number and upregulated genes such as Pgc-1α involved in mitochondrial biogenesis. The foregoing results suggest that local cryotherapy increases CREB transcription and upregulates CREB-targeting genes in a manner dependent on cold stimulation frequency and duration. This information may serve as an impetus for further investigations into local cryotherapy as a treatment for sports-related skeletal muscle trauma.

Many dioecious plants have sex chromosomes that are cytologically heteromorphic, but about half of species lack cytological differences between males and females and are thus homomorphic. Very little is known about the size and content of the non-recombining sex-determining region (SDR) in these species. Here, we assess the size and content of the SDR of the diploid dioecious herb Mercurialis annua, which has homomorphic sex chromosomes and shows signatures of mild Y-chromosome degeneration. We used RNAseq to identify new Y-linked markers for M. annua. Twelve of 24 transcripts with male-specific and male-biased expression could only be PCR-amplified from males and are thus Y-linked. We found a further six Y-linked sequences that were present in males but not females using genome capture data from multiple populations. We used the Y-linked sequences to identify and sequence 17 sex-linked bacterial artificial chromosomes (BACs), which form 11 groups of non-overlapping sequence, covering a total sequence length of about 1.5 Mb. Content analysis of this region suggests it is enriched for repeats, has a low gene density and contains few candidate sex-determining genes. The BACs map to a subset of the sex-linked region of the genetic map, which is estimated to be at least 14.5 Mb. This is substantially larger than estimates for other dioecious plants with homomorphic sex chromosomes, especially given the small genome size of M. annua. Our data provide a rare, high-resolution view of the homomorphic Y chromosome of a dioecious plant.