Artificial Intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use ChatGPT holds a prom-inent position using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for gen-erating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT in-tegration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex data sets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with an array of acute and chronic diseases, in humans. However, their specific effects on the stem cells remain unclear. Here, we report the effects of PM collected from Jeddah city on bone marrow mesenchymal stem cells (BM-MSCs) on proliferation, cell death, related gene expression and systems biological analysis aiming to understand the underlying mechanisms. Two different sizes (PM_2.5-₁₀) were tested in vitro at various concentrations (15 to 300 µg/ml) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM_2.5 increased BM-MSCs proliferation, while higher concentrations decreased it. PM₁₀ decreased BM-MSCs proliferation in a concentration-dependant manner. The X-Ray Fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses showed that heavy metals were associated with signalling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential regulation of the apoptosis genes (BCL2, BAX); upregulation of inflammation associated genes (TNF-a and IL-6) and downregulation of cell cycle regulation gene (P53). We conclude that PM could affect different cellular functions and predispose to debilitating diseases.

Cerebellar ataxia, neuronopathy, and vestibular areflexia syndrome (CANVAS) is caused by biallelic pathogenic expansions, or compound heterozygosity with other pathogenic variants in the RFC1 gene. CANVAS is estimated to be underdiagnosed, both because of the lack of formal diagnostic criteria and molecular challenges that translate to lesser access and high cost of routine testing. Our aim was to address the need for making CANVAS genetic testing routine, by designing a streamlined two-step PCR consisting of a short-allele screening PCR and a confirmatory PCR with fragment capillary electrophoresis detection. Exome sequencing of RFC1 was additionally foreseen to resolve potential compound heterozygosity cases. Specificity of our approach was evaluated using ataxia patients with known non-CANVAS diagnoses, and optimized using Southern blot confirmed CANVAS patients. We evaluated our approach by testing patients consecutively referred for clinically suspected CANVAS using first the two-step PCR, followed by exome sequencing. Our approach was able to accurately identify negative and confirm positive cases in prospectively collected suspected CANVAS patients presenting with at least three typical clinical signs. The proposed testing approach provides an alternative method able to clearly distinguish between CANVAS negative and positive cases and can be easily incorporated into the genetic diagnostic laboratory workflow.

Background: Alfalfa, the most economically important forage legume worldwide, features modest genetic progress due to long selection cycles and large extent of non-additive genetic variance associated with its autotetraploid genome. Methods: To improve the efficiency of genomic selection in alfalfa, we explored the effects of genome parametrization (as autotetraploid and diploid dosage, plus allele ratios) and SNP marker subsetting (all available SNPs; only genic regions; only non-genic regions) on genomic regressions, together with various levels of filtering on reading depth and missing rates. We used Genotyping by Sequencing-generated data and focused on traits of different genetic complexity, i.e., dry biomass yield in moisture-favorable (FE) and drought stress (SE) environments, leaf size, and onset of flowering, assessed on 143 genotyped plants from a genetically-broad European reference population and their phenotyped half-sib progenies. Results: On average, allele ratio improved the predictive ability compared with other genome parametrizations (+7.9% vs. tetraploid dosage, +12.6% vs. diploid dosage), SNP subsetting offered an advantage compared with any tested subsettings (+3.7% vs. genic regions, +7.6% vs. non-genic regions). However, when focusing on specific traits, different combinations of genome parametrization and subsetting reached better performances. We also released Legpipe2, a SNP calling pipeline tailored for reduced representation (GBS, RAD) medium-sized genotyping experiments.

Bacteriophages (phages) are potential alternatives to chemical antimicrobials against pathogens of public health significance. Understanding the diversity and host specificity of phages is important for developing effective phage biocontrol approaches. Here, we assessed the host range, morphology, and genetic diversity of eight Salmonella enterica phages isolated from a wastewater treatment plant. The host range analysis revealed that six out of eight phages lysed more than 81% of the 43 Salmonella enterica isolates tested. The genomic sequences of all phages were determined. Whole genome sequencing data (WGS) data revealed that phage genome sizes ranged from 41 to 114 kb with GC contents be-tween 39.9 and 50.0 %. Two of the phages SB13 and SB28 represent new species Epsep-timavirus SB13 and genera Macdonaldcampvirus, respectively as designated by the In-ternational Committee for the Taxonomy of Viruses (ICTV) as per genome based taxonomic classification. One phage (SB18) belonged to the Myoviridae morphotype while the re-maining phages belonged to the Siphoviridae morphotype. The gene content analyses showed that none of the phages possessed virulence, toxin, antibiotic resistance, type I-VI toxin-antitoxin modules or lysogeny genes. Three (SB3, SB15 and SB18) out of the eight phages possessed tailspike proteins. Whole genome-based phylogeny of the eight phages with their 113 homologs revealed three clusters A, B, C and seven subclusters (A1, A2, A3, B1, B2, C1 and C2). While cluster C1 phages were predominantly isolated from animal sources, cluster B contained phages from both wastewater and animal sources. The broad host range of these phages highlights their potential use to control the presence of S. enterica in foods.

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of estrogen signaling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear estrogen signaling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of estrogen in CRC through various genomic and non-genomic signaling pathways involving membrane and nuclear estrogen receptors. Furthermore, we examine the interplay between estrogen receptors and other signaling pathways, in particular the Wnt/-catenin proliferative pathway and hypoxia in shaping biological sex differences and estrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting estrogen signaling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

Canine mammary tumors (CMTs) are among the most common disease in female dogs and share similarities with human breast cancer, which have placed these animals as a model of study in comparative oncology. Metabolic reprogramming is one of them and is known as a hallmark of carcinogenesis whereby cells undergo adjustments to supply the high bioenergetic and biosynthetic demands of rapidly proliferating cells. However, such alterations are also vulnerabilities that may serve as therapeutic strategies which have been tested mostly in human clinical trials, but poorly explored in CMTs. In this dedicated review, we compilated the metabolic changes described for CMTs emphasizing the metabolism of carbohydrates, amino acids, lipids, and mitochondrial function. We observed here key factors associated with the presence and aggressiveness of CMTs, such as the increase in glucose uptake followed by enhanced anaerobic glycolysis via upregulation of glycolytic enzymes, changes in glutamine catabolism due to overexpression of glutaminases, raise in fatty acid oxidation and distinct effects depending on the lipid saturation, in addition to mitochondrial DNA which is a hotspot for mutations. Therefore, more attention should be paid to this topic given that targeting metabolic fragilities could improve the outcome of CMTs.

Pediatric obstructive sleep apnea (OSA) has significant negative effects on health and behavior in childhood including depression, failure to thrive, neurocognitive impairment, and behavioral issues. It is strongly associated with an increased risk for chronic adult disease such as obesity and diabetes, accelerated atherosclerosis, and endothelial dysfunction. Accumulating evidence suggests that adult-onset non-communicable diseases may originate from early life through a process by which an insult applied at a critical developmental window causes long-term effects on the structure or function of an organism. Recently, much attention has been paid to the role of epigenetic mechanisms in the pathogenesis of adult disease susceptibility. Epigenetic mechanisms that influence adaptive variability include histone modifications, non-coding RNAs, and DNA methylation. This review will highlight what is currently known about the phenotypic associations of epigenetic modifications in pediatric OSA and will emphasize the importance of epigenetic changes as both modulators of chronic disease and potential therapeutic targets.

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. Pancreatic ductal adenocarcinoma (PDA) is the most common (90%) and aggressive type of pancreatic cancer. Genomic analyses of PDA specimens have identified the recurrent genetic mutations that drive PDA initiation and progression. However, the underlying mechanisms that further drive PDA metastasis remain elusive. Despite many attempts, no recurrent genetic mutation driving PDA metastasis has been found, suggesting that PDA metastasis is driven by epigenetic fluctuations rather than genetic factors. Therefore, establishing epigenetic mechanisms of PDA metastasis would facilitate the development of successful therapeutic interventions. In this review, we provide a comprehensive overview on the role of epigenetic mechanisms in PDA as a critical contributor on PDA progression and metastasis. In particular, we explore the recent advancements elucidating the role of nucleosome remodeling, histone modification, and DNA methylation in the process of cancer metastasis.

Huntington's disease (HD) is an inherited neurodegenerative disorder that usually starts during midlife with progressive alterations of motor and cognitive functions. The disease is caused by a CAG repeat expansion within the huntingtin gene leading to severe striatal neurodegeneration. Recent studies conducted on pre-HD children highlight early striatal developmental alterations starting as soon as 6 years old, the earliest age assessed. These findings, in line with data from mouse models of HD, raise the question of when during development do the first disease-related striatal alterations emerge or whether they contribute to the later appearance of the neurodegenerative features of the disease. In this review we will describe the different stages of striatal network development and then discuss recent evidence for its alterations in rodent models of the disease. We argue that a better understanding of the striatum’s development should help in assessing aberrant neurodevelopmental processes linked to the HD mutation.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

Wastewater-based epidemiology (WBE) has emerged as a key method for continuous monitoring of COVID-19 prevalence including circulating SARS-CoV-2 lineages. WBE addresses limitations of traditional clinical COVID-19 surveillance such as clinical test availability, fluctuating testing rates and increased reliance on rapid antigen tests. Our study in Perth, Western Australia, found a significant positive correlation between SARS-CoV-2 concentrations in wastewater and clinical PCR positivity rates (rs = 0.772; p < 0.001) over an 18-month period that included four successive COVID-19 waves. A strong positive correlation was apparent between the proportions of SARS-CoV-2 lineages in wastewater and clinical cases within the same region (rs = 0.728; p < 0.001), including earlier detection of Omicron and recombinant lineages in wastewater before clinical case confirmation. The successful integration of WBE with healthcare data underscores its critical role in enhancing public health decision-making and pandemic management. This approach not only demonstrates the value of WBE in current global health surveillance efforts but also highlights the potential of WBE to address future public health challenges, as a comprehensive disease monitoring and response approach.

Toxins present in cigarette and e-cigarette smoke constitute a significant cause of illnesses and are known to have fatal health impacts. Specific mechanisms by which toxins present in smoke impair cell repair are still being researched and are of prime interest for developing more effective treatments. Current literature suggests toxins present in cigarette smoke and aerosolized e-vapor trigger abnormal intercellular responses, damage mitochondrial function, and consequently disrupt the homeostasis of the organelle’s biochemical processes by increasing reactive oxidative species. Increased oxidative stress sets off a cascade of molecular events, disrupting optimal mitochondrial morphology and homeostasis. Furthermore, smoking-induced oxidative stress may also amalgamate with other health factors to contribute to various pathophysiological processes. An increasing number of studies show that toxins may affect mitochondria even though exposure to secondhand or thirdhand smoke. This review assesses the impact of toxins present in tobacco smoke and e-vapor on mitochondrial health, networking, and critical structural processes including mitochondria fission, fusion, hyperfusion, fragmentation, and mitophagy. The efforts are focused on discussing current evidence linking toxins present in first, second, and thirdhand smoke to mitochondrial dysfunction

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes asso-ciated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with non-alcoholic fatty liver disease (MAFLD). We did not observe a significant association between the investigated SNPs and COVID-19 severity. While the IFNAR2 rs2236757 A allele correlated with higher creatinine levels upon admission and the G allele with lower band neu-trophils upon discharge, these findings require further investigation. The distribution of OAS gene polymorphisms (rs10774671, rs10735079 did not differ between MAFLD and non-MAFLD patients. Our study population's distribution of ACE2 rs2074192 genotypes and alleles differed from the European reference population. Overall, our findings suggest that these specific SNPs may not be major contributors to COVID-19 severity in our patient population, highlighting the potential role of other genetic factors and environmental influences.

After human genome sequencing and rapid changes in genome sequencing methods, we have entered in the era of rapidly accumulating genome-sequencing data. This has poses development of several types of methods for representing results of genome sequencing data. Circular genome visualizations tools are also critical in this area as they provide rapid interpretation and simple visualization of overall data. In the last 15 years, we have seen rapid changes in circular visualization tools after the development of the circos tool with 1–2 tools published per year. Herein we have summarized and revisited all these tools until the third quarter of 2018.

The cornea is the optical window to the brain. Its optical and structural properties are responsible for optical transparency and vision. The shape, elasticity, rigidity or stiffness are given by its biomechanical properties, whose stability results in ocular integrity and intraocular pressure dynamics. Here, we report in vivo observation of structural changes and biomechanical alterations of the human cornea induced by acoustic wave pressure within the frequency range of 50-350 Hz and 90 dB of sound pressure level. Central corneal thickness (CCT) and eccentricity (e2) were measured using Scheimpflug imaging and biomechanical properties [corneal hysteresis (CH) and intraocular pressure (IOP] were assessed with air-puff tonometry in 6 young healthy subjects. At the specific 150 Hz acoustic frequency, the variation in CCT and e2 were of 0.058 and 7.33 µm, respectively. Biomechanical alterations were also observed in both IOP (decrease of 3.60 mmHg) and CH that showed an increase of 0.40 mmHg.

The field of epigenetics, which explores how heritable traits or stable alterations of cell functions occur without changes to the DNA sequence and how environmental factors affect gene expression, is rapidly advancing. Epigenetics plays a critical role in memory formation, learning, and cognitive functioning, effectively bridging genetics with environmental influence. Maternal behavior in rats, for instance, can modify the stress response of their offspring through epigenetic mechanisms such as histone acetylation and DNA methylation. Understanding neurodegenerative diseases like Parkinson's disease (PD) depends on comprehending the mechanisms of epigenetic regulation. Epigenetic modifications, which alter proteins and DNA structure without changing the DNA sequence, can activate or suppress gene expression, assisting organisms in adapting to environmental changes. These modifications may influence genes involved in inflammation, synaptic plasticity, and neuroprotection, potentially contributing to cognitive deficits in PD patients. MicroRNAs (miRNAs), histone modifications, and DNA methylation are the epigenetic mechanisms that significantly influence cell differentiation and maintain normal cellular activity. Understanding the intricate molecular processes of epigenetics could lead to more targeted and effective therapies. Despite numerous findings on how epigenetics affects cognitive alterations in PD patients, only some studies coordinate and integrate these results. Here, we summarize recent findings on how epigenetic changes impact gene expression linked to cognitive impairments in PD.

Legionella pneumophila can cause a large panel of symptoms beside the classic pneumonia presentation. We present here a case of fatal nosocomial cellulitis in an immunocompromised patient followed, a year later, by a second case of legionnaires’ disease in the same ward. While the first one was easily assumed as nosocomial based on the date of symptoms onset, the other case needed to rely on clear typing results to be either assigned as nosocomial and related to the same environmental source as the first one, or community acquired. To untangle this specific question, we applied Core-genome MultiLocus Typing (MLST), whole-genome Single Nucleotide Polymorphism and whole-genome MLST methods to a collection of 36 Belgian and 41 international sequence-type 1 (ST1) isolates using both thresholds recommended in the literature and tailored threshold based on local epidemiological data. Based on the thresholds applied to cluster isolates together, the three methods gave different results and no firm conclusion about the nosocomial setting of the second case could been drawn. Our data highlight that despite promising results in the study of outbreaks and for large scale epidemiological investigations, NGS typing methods applied to ST1 outbreak investigation still need standardization regarding both wet-lab protocols and bioinformatics. A deeper evaluation of L. pneumophila evolutionary clock is also required to increase our understanding of genomic differences between isolates sampled during a clinical infection and in environment.

Functional copy number alterations (fCNAs) are DNA copy number changes with concordant differential gene expression. These are less likely to be bystander genetic lesions and could serve as robust and reproducible tumor biomarkers. To identify candidate fCNAs in neuroendocrine tumors (NETs), we integrated chromosomal microarray (CMA) and RNA-seq differential gene expression data from 31 pancreatic (pNET) and 33 small bowel neuroendocrine tumors (sbNET). Tumors were resected from 47 early disease progression (24 months) patients. Candidate fCNAs that accurately differentiated these groups in this discovery cohort were then replicated using fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded (FFPE) tissues in a larger validation cohort of 60 pNETs and 82 sbNETs (52 early and 65 late disease progression samples). Logistic regression analysis determined the predictive ability of these biomarkers as well as the assay performance metrics of sensitivity, specificity, and area under the curve. Our results indicate that copy number changes at chromosomal loci 4p16.3, 7q31.2, 9p21.3, 17q12, 18q21.2, and 19q12 may be used as diagnostic and prognostic NET biomarkers. This involves a rapid, cost-effective approach to determine primary tumor site for patients with metastatic liver NETs and to guide risk stratified therapeutic decisions.

Molecular markers, including Simple Sequence Repeat (SSR), Single Nucleotide Polymorphism (SNP), and Intron Length Polymorphism (ILP), are widely utilized in crop improvement and population genetics studies. However, these marker resources remain insufficient for Musa species. In this study, we developed genome-wide SSR, SNP, and ILP markers from Musa and its sister species, creating a comprehensive molecular marker repository for the improvement of Musa species. This database contains 2115474 SSR, 63588 SNP, and 91547 ILP markers developed from thirteen Musa species and two of its relative species. We found that 77% of the SSR loci are suitable for marker development; 38% of SNP markers originated from the genic region, and transition mutations (C↔T; A↔G) were more frequent than transversion. The database is freely accessible and follows a ‘three-tier architecture,’ organizing marker information in MySQL tables. It has a user-friendly interface, written in JavaScript, PHP, and HTML code. Users can employ flexible search parameters, including marker location in the chromosome, transferability, polymorphism, and functional annotation, among others. These distinctive features distinguish the Musa Marker Database (MMdb) from existing marker databases by offering a novel approach that is tailored to the precise needs of the Musa research community. Despite being an in silico method, searching for markers based on various attributes holds promise for Musa research. These markers serve various purposes, including germplasm characterization, gene discovery, population structure analysis, and QTL mapping.

Chronic exposure to noise can cause several extraordinary effects and involve all the systems of the human organism. In addition to cardiovascular, gastrointestinal and immune effects, the data in the literature show alterations in behavioral disturbances, in memory capacity and cognitive performance. Through this systematic review, the authors try to find out which are the main neurobehavioral alterations, in case of occupational exposure to noise. Literature review included articles published in the major databases (PubMed, Cochrane Library, Scopus), using a combina-tion of some relevant keywords. This online search yielded 4434 references; after selection, the authors analyzed 41 articles (4 narrative reviews and 37 original articles). From this analysis, it appears that main symptoms are related to psychological distress, annoyance, sleep disturbances, cognitive performance. Regarding tasks, the most frequent employments concern school staff, followed by employees from various industrial sectors and office workers. Although the causes are still widely debated, it is essential to protect these workers against chronic exposure to noise. In fact, in addition to a hearing loss, they can manifest many other related discomforts over time and compromise their full working capacity, as well as expose them to a greater risk of accidents or absences from work.

Genomic selection (GS) can accelerate variety improvement when training set (TS) size, and its relationship with the breeding set (BS) are optimized for prediction accuracies (PA) of genomic prediction (GP) models. Sixteen GP algorithms were run on phenotypic best linear unbiased predictors (BLUPs) and estimators (BLUEs) of resistance to both fall armyworm (FAW) and maize weevil (MW) in a tropical maize panel. For MW resistance, 37% of the panel was the TS, and BS was the remainder whilst for FAW, random-based training sets (RBTS) and pedigree-based training sets (PBTS) were designed. PAs achieved with BLUPs varied from 0.66 to 0.82 for MW resistance traits, and, for FAW resistance, 0.694 to 0.714 for RBTS of 37%, and 0.843 to 0.844 for RBTS of 85%, and, these were at least two-fold those from BLUEs. For PBTS, FAW resistance PAs were generally higher than those for RBTS, except for one dataset. GP models generally showed similar PAs across individual traits whilst the TS designation was determinant since a positive correlation (R=0.92***) between TS size and PAs was observed for RBTS and, for the PBTS, it was negative (R=0.44**). This study pioneers the use of GS for maize resistance to insect pests in sub-Saharan Africa.

The advancement of sequencing technology and molecular breeding methods have provided technical support and assurance for accurate breeding. Genomic Selection (GS) utilizes genomic information to improve livestock breeding and, it is more accurate and more efficient than traditional selection methods. GS has been widely applied in domestic animals breeding, especially in cattle. However, there is still limited study on the application and research of GS in sheep and goat. In this paper, we outlined the principle, analysis methods, the influential factors of GS, and elaborated on the research progress, challenges, and prospects of applying GS in sheep and goat breeding. Through the review of these aspects this paper is expected to provide valuable references for the implementation of GS in the field of sheep and goat breeding.

The advancement of precision medicine in medical care has led behind the conventional symptom-driven treatment process by allowing early risk prediction of disease through improved diagnostics and customization of more effective treatments. It is necessary to scrutinize overall patient data alongside broad factors to observe and differentiate between ill and relatively healthy people to take the most appropriate path toward precision medicine, resulting in an improved vision of biological indicators that can signal health changes. Precision and genomic medicine combined with artificial intelligence have the potential to improve patient healthcare. Patients with less common therapeutic responses or unique healthcare demands are using genomic medicine technologies. AI provides insights through advanced computation and inference, enabling the system to reason and learn while enhancing physician decision-making. Many cell characteristics, including gene up-regulation, proteins binding to nucleic acids, and splicing, can be measured at high throughput and used as training objectives for predictive models. Researchers can create a new era of effective genomic medicine with the improved availability of a broad range of data sets and modern computer techniques such as machine learning. This review article has elucidated the contributions of ML algorithms in precision and genome medicine.

Wheat (Triticum aestivum L.) breeding programs can take over a decade to release a new variety. However, new methods of selection such as genomic selection (GS) must be integrated to decrease the time it takes to release new varieties to meet the demand of a growing population. The implementation of GS into breeding programs is still being explored, with many studies showing its potential to change wheat breeding through achieving higher genetic gain. In this review, we explore the integration of GS for a wheat breeding program by redesigning the traditional breeding pipeline to implement GS. We propose implementing a two-part breeding strategy by differentiating between population improvement and product development. The implementation of GS in the product development pipeline can be integrated into most stages and can predict within and across breeding cycles. Additionally, we explore optimizing the population improvement strategy through GS recurrent selection schemes to reduce crossing cycle time and significantly increase genetic gain. The recurrent selection schemes can be optimized for parental selection, maintenance of genetic variation, and optimal cross-prediction. Overall, we outline the ability to increase the genetic gain of a breeding program by implementing GS and a two-part breeding strategy.

The novel respiratory disease COVID-19 has reached the status of worldwide pandemic and large efforts are currently being undertaken in molecularly characterizing the virus causing it, SARS-CoV-2. The genomic variability of SARS-CoV-2 specimens scattered across the globe can underly geographically specific etiological effects. In the present study, we gather the 48,635 SARS-CoV-2 complete genomes currently available thanks to the collection endeavor of the GISAID consortium and thousands of contributing laboratories. We analyze and annotate all SARS-CoV-2 mutations compared with the reference Wuhan genome NC_045512.2, observing an average of 7.23 mutations per sample. Our analysis shows the prevalence of single nucleotide transitions as the major mutational type across the world. There exist at least three clades characterized by geographic and genomic specificity. In particular, the clade G, prevalent in Europe, carries a D614G mutation in the Spike protein, which is responsible for the initial interaction of the virus with the host human cell. Our analysis may drive local modulation of antiviral strategies based on the molecular specificities of this novel virus.

Metabolic bone diseases cover a broad spectrum of disorders that share alterations of bone metabolism leading to a defective skeleton, associated with increasing morbidity, disability, and mortality. There is a close connection between the etiology of metabolic bone diseases and genetic factors, being TP53 one of the genes associated therewith. The single nucleotide polymorphism (SNP) Arg72Pro of TP53 is a genetic factor associated with several pathologies, including cancer, stroke and osteoporosis. Here, we aim to analyze the influence of the TP53 Arg72Pro SNP on bone mass in the humanized Tp53 Arg72Pro knock-in mice. This work reported on the influence of TP53 Arg72Pro polymorphism in bone microarchitecture, OPG gene expression and apoptosis bone status. The results showed that the proline variant of TP53 Arg72Pro polymorphism (Pro72-p53) was associated with deteriorated bone tissue, lower OPG/RANK ratio and lower apoptosis in bone tissue. In conclusion, the TP53 Arg72Pro polymorphism modulates bone microarchitecture and may be a genetic biomarker to identify individuals with an increased risk of suffering metabolic bone alterations

Background: Alcohol consumption is associated with the development of cardiovascular diseases, cancer, and liver disease. The biological mechanisms are still largely unclear. Here, we aimed to use an agnostic approach to identify phenotypes mediating the effect of alcohol on various diseases. Methods: We performed an agnostic association analysis between alcohol consumption (red, and white wine, beer/cider, fortified wine, and spirits) with over 7,800 phenotypes from the UK biobank comprising 223,728 participants. We performed Mendelian randomisation analysis to infer causality. We additionally performed a Phenome-wide association analysis and a mediation analysis between alcohol consumption as exposure, traits in causal relationship with alcohol consumption as mediators, and various diseases as outcome. Results: Of 45 traits in association with alcohol consumption, 20 were in causal relationship with alcohol consumption. Gamma glutamyltransferase (GGT; β=9.44; CI,5.94-12.93; Pfdr=9.04×10-7), mean sphered cell volume (β=0.189; CI,0.11-0.27; Pfdr=1.00×10-4), mean corpuscular volume (β=0.271; CI,0.19-0.35; Pfdr=7.09×10-10) and mean corpuscular haemoglobin (β=0.278; CI,0.19-0.36; Pfdr=1.60×10-6) showed the strongest causal relationships. We also identified GGT and physical activity as mediators causing liver cirrhosis and alcohol dependence. Conclusion: Our study provides evidence of causality between alcohol consumption and 20 traits and a mediation effect for physical activity on health consequences of alcohol consumption.

GS provides exciting opportunities to rapidly identify a diagnosis in critically ill newborns and children with rare genetic conditions. But there are good reasons to remain cautious about the broad implementation of these strategies in babies and children. At best, rapid GS leads to diagnoses in many infants in highly selected populations. It sometimes leads to beneficial and changes in management. Parents and physicians both often find these results useful. We don’t know how useful such testing will be in the general population. It is almost inevitable that genetic counseling will be more challenging in a more general population. We don’t know how often GS helps improve outcome and survival or reduce symptoms in babies who receive a molecular diagnosis. We don’t know the relative cost-effectiveness of whole genome, whole exome, or targeted panels in different populations. We don’t know the relative contribution of a molecular diagnosis to the decision to withdraw life support. Each of these concerns will require careful study of both the technology and the ethical issues to allow us to harness the potential of these new technologies while avoiding foreseeable problems. Studies are underway to see how the tests are used in general populations. These studies should generate important information to guide clinicians and policymakers. In the meantime, parents should know that genetic results sometimes confirm an already suspected dismal prognosis and sometimes yield only ambiguous findings. Anticipatory discussions should try to give parents a realistic understanding of the likely impact of a genetic diagnosis. Both doctors and parents should recognize that the clinical usefulness of diagnostic genomic testing in newborns is a work in progress. We are only a decade into the age of true genomic medicine. We still have much to learn.

Turmeric is highly tolerant to several climatic changes and can grow under high temperatures and moderate drought conditions. This herb is very much dependant on optimum rainfall, optimum heat with less chilling or freezing conditions. These conditions if are more than normal would tend to reduce the yields of the crops and also effect the productivity. To reduce such drastic yield losses certain conventional plant breeding methods were employed but were very less effective compared to plant biotechnology. To reduce these loses by stresses, extensive and effective molecular biology methods were employed which identifies the genes that are stress responsive along with certain methods like gene transfer, genetic engineering was also known to be effective. All these methods are quite helpful in mitigating the yield losses and promoting healthy growth in the plants. The maintenance of rhizome size, curcumin content, essential oils etc. is very much necessary for the turmeric crop because of its role, especially in the medical field. Therefore, the yield losses are reduced to a maximum extent so that development of smart turmeric is easy and crop designing is possible only with the advanced techniques involved in agriculture biotechnology.

Cervical cancer is the fourth common cancer amongst women worldwide. Environmental factors such as smoking and obesity, and recurrent infection by high-risk human papillomavirus subtypes are known to promote progression towards invasive cervical disease. Infection by high-risk HPV is necessary in most cases but not sufficient to develop invasive cervical cancer. Despite a predicted genetic heritability of between 27-36%, known genetic susceptibility loci that may be tumorigenic or influence host response to infection, only account for a small fraction of heritable risk factors so far. Various biobank-driven population based studies and meta-analyses have found corroborative evidence for several risk variants at the 6p21.3 locus (HLA), while many reports of variants outside the HLA region remain to be validated in other cohorts. Here, we review cervical cancer susceptibility variants arising from recent genome-wide association studies and meta-analysis in large cohorts and propose 2q14 (PAX8), 17q12 (GSDMB), and 5p15.33 (CLPTM1L) as consistently replicated non-HLA cervical cancer susceptibility loci. We further discuss the available evidence for these loci, knowledge gaps, future perspectives, and the potential impact of these findings on precision medicine strategies to combat cervical cancer.

Prostate cancer is a leading cause of death among men but its genomic characterization and best therapeutic strategy are still under debate. The Genomic Fabric Paradigm (GFP) considers the transcriptome as a multi-dimensional mathematical object subjected to a dynamic set of expression correlations among the genes. Here, GFP is applied to gene expression profiles of three (one primary, and two secondary) cancer nodules and the surrounding normal tissue from a surgically removed prostate tumor. GFP was used to determine the regulation and rewiring of the P53 signaling, apoptosis, prostate cancer and several other pathways involved in survival and proliferation of the cancer cells. Genes responsible for the block of differentiation, evading apoptosis, immortality, insensitivity to anti-growth signals, proliferation, resistance to chemotherapy and sustained angiogenesis were found as differently regulated in the three cancer nodules with respect to the normal tissue. The analysis indicates that even histo-pathologically equally graded cancer nodules from the same tumor have substantially different transcriptomic organizations, raising legitimate questions about the validity of meta-analyses comparing large populations of healthy and cancer humans. The study suggests that GFP may provide a personalized alternative to the biomarkers’ approach of cancer genomics.

Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis. This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.

Chromosomal rearrangements in N. gonorrhoeae and N. meningitidis were studied with the determination of mobile elements and their role in rearrangements. The results of whole-genome sequencing and de novo genome assembly for 50 N. gonorrhoeae isolates collected in Russia were compared with 96 genomes of N. gonorrhoeae and 138 genomes of N. meningitidis from the databases. Rearrangement events with the determination of the coordinates of syntenic blocks were analyzed using the SibeliaZ software, the minimum number of events that allow one genome to pass into another was calculated using the DCJ-indel model using the UniMoG program. Population-level analysis revealed a stronger correlation between changes in the gene order and phylogenetic proximity for N. meningitidis in contrast to N. gonorrhoeae. Mobile elements were identified, including Correa elements, Spencer-Smith elements (in N. gonorrhoeae), Neisserial intergenic mosaic elements, IS elements of IS5, IS30, IS110, IS1595 groups, Nf1-Nf3 prophages, NgoФ1-NgoФ9 prophages, Mu-like prophages Pnm1, Pnm2, MuMenB (in N. meningitidis). More than 44% of the observed rearrangements most likely occurred with the participation of mobile elements, including prophages. No differences were found between the Russian and global N. gonorrhoeae population both in terms of rearrangement events and in the number of transposable elements in genomes.

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM). Aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this aim, one hundred and seventeen T2DM patients without (n=42) and with (n=75) DKD (DKD I-III upon KDIGO classification) were evaluated; total albumin concentration (tHA) was quantified by bromocresol green assay, while structural alterations were profiled assessed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The concentrations of albumin in native (eHA, effective albumin) and reduced (rHA) forms were then assessed. HRMS analyses showed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied along the stages of progressive renal failure, and alterations dose-dependently correlated with renal dysfunction. ROC curves analysis showed a significantly higher sensitivity and specificity of eHA and rHA with respect to tHA for the diagnosis of DKD. Importantly, at multivariable logistic regression analysis, eHA was identified as independent predictor of DKD.

Heterosis plays a significant role in enhancing variety, boosting yield, and raising economic value, but the molecular mechanism is still unclear. We analyzed the transcriptomes and 3D genomes of hybrid (F1) and its parents (w30 and 082). Analysis of the expression revealed a total of 485 specially expressed genes (SEGs), 173 differentially expressed genes (DEGs) above parental expression level, more actively expressed genes and up-regulated DEGs in F1. Further study revealed that the DEGs detected in F1 and its parents were mainly involved in response to auxin, plant hormone signal transduction, DNA metabolic process, Purine metabolism, starch and sucrose metabolism, which suggested that these biological processes may play a crucial role in the heterosis of B. rapa. The analysis of 3D genome data revealed that hybrid F1 tend to contain more transcriptionally active A compartments after hybridization. Additionally, F1 had a smaller TAD (topologically associated domain) genome length, but the number was the highest, and the expression change of activated TAD was higher than repressed TAD. More specific TAD boundaries were detected between parents and F1. Subsequently, 140 DEGs with genomic structural variants were selected as potential candidate genes. Among them, we found two DEGs with consistent expression changes in A/B compartments and TADs. Our findings suggest that genomic structural variants, such as TADs and A/B compartments, may affect gene expression and contribute to heterosis in B. rapa. This study provides further insight into the molecular mechanism of heterosis in B. rapa.

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of Reactive Oxygen Species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes of gravitational force even if published data on germ cell models are scarce. To gain more insights into the mechanisms of male germ cell response to altered gravity, a 3D cell culture model has been established from TCam-2 cells, a seminoma-derived cell line considered the only human cell line available to study in vitro mitotically active human male germ cells. TCam-2 cell spheroids were cultured for 24 hours under unitary gravity (Ctr) or simulated microgravity (s-microgravity) conditions, these last ones were obtained using the Random Positioning Machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels has been observed after RPM exposure. In line with these results a trend of protein and lipid oxidation increase, and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis by Transmission Electron Microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, being GPX1, NCF1, and CYBB downregulated, whereas NOX4 and HMOX1 upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated to the observed mitochondria alteration. All together, these data demonstrate TCam-2 spheroid sensitivity to acute SM exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow to overcome the exposure to altered gravitational force.

Autism Spectrum disorder (ASD) and intellectual disability (ID) are the most frequent develop-mental disorders with a prevalence between 3% and 5% of the population. In addition, both ASD and ID can be found in the same patient. Mutations in several genes involved in the epigenetic regulation of gene expression have been linked to different ID associated with ASD features including alterations of the ly-sine-acetyltransferase 6A (KAT6A) gene in KAT6A syndrome. KAT6A enzyme participates in a wide range of critical cellular functions such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiolog-ical alterations in fibroblasts derived from three patients harboring KAT6A mutations. We ad-dressed survival in stress medium, histone acetylation, protein expression patterns and tran-scriptome analysis as well as cell bioenergetics. In addition, we evaluated the therapeutic effec-tiveness of epigenetic modulators and mitochondrial boosting agents such as pantothenate and L-carnitine in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly correct the mutant phe-notype in cellular models of KAT6A syndrome.

Aging is a complex biological process, with gradual and progressive decline in structure and function in many organ systems. Our objective is to determine if structural changes produced by aging, vary with sex, in a stressful situation such as dehydration. The expression of Slc12a3 mRNA in renal cortex, α-smooth muscle actin (α-SMA) and fibronectin, was evaluated in male and female rats aged 3 and 18 months submitted or not to water deprivation (WD) for 48 hours. When comparing ages, 18-month-old males showed lower expression of Slc12a3 mRNA than 3-month-old males, and control and WD 18-moth-old male and female rats exhibited higher expression of α-SMA than respective 3-month-old rats. Fibronectin was higher in both control and WD 18-month-old males than respective 3-month-old males. In females, only control 18-month-old rats showed higher fibronectin than control 3-month-old rats. When we compared sex, control and WD 3-month-old female rats had lower expression of Slc12a3 mRNA than re-spective males. WD 18-month-old male rats presented higher expression of fibronectin and α-SMA than WD 18-month-old female rats. When we compared hydric condition, WD 18-month-old males displayed lower relative expression of Slc12a3 mRNA and higher α-SMA expression than control 18-month-old males. Aging, sex, and dehydration lead to alteration in kidney structure.

Cells receive external stimuli to incur structural and functional damages. On scanning acoustic microscopy (SAM), speed-of-sound (SOS), attenuation-of-sound (AOS), and thickness values are plotted on the screen to create cellular images, which are related to stiffness, viscosity, and cell size, respectively. The obtained digital data compared using statistical analysis. We aimed to investigate the effects of anticancer drugs, acidic fluids, and heat effects on the cells by using SAM. Anticancer drug cisplatin induced cancer cell apoptosis/necrosis and regeneration in culture, causing elevated SOS, reduced AOS, and thickness. During a more prolonged incubation, the SAM values fluctuated differently between the cisplatin-treated and untreated cells. The tannic and acetic acid and microwave stimuli induced SOS and AOS elevations. These stimuli altered the cell size, number, differentiation, viscosity, and stiffness, which corresponded well to the fluctuation of the SOS and AOS values after incubation. Different anticancer drugs interacted with cancer cells to induce the characteristic alterations of the SAM values. These structural and mechanical alterations induced in cells was difficult to observe on light microscopy. Cellular damages were statistically compared between different stimuli and time-lapse cellular changes were observed using a SAM analysis. SAM is a useful modality to evaluate cellular damage.

We performed a comprehensive analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin. We aimed to describe the genomic landscape of AS in a cohort of 143 cases of AS profiled by Caris Life Sciences. Data of Next Generation Sequencing (NGS) with a 592 gene panel was available for the entire cohort. Fifty-three cases had data of Whole Exome Sequencing (WES) which we used to study the microenvironment phenotype. Immuno-therapy (IO) response biomarkers: Tumor Mutation Burden (TMB), Microsatellite Instability (MSI) and PD-L1 status were included. IO-response markers were present in 36.4% of the cohort and in 65% of head and neck AS (H/N-AS) (p<0.0001). H/N-AS cases had predominantly muta-tions in TP53 (50.0%, p=0.0004), POT1 (40.5%, p<0.0001) and ARID1A (33.3%, p=0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p<0.0001), HRAS (16.1%, p=0.0377), and PI3KCA (16.1%, p=0.2352). A microenvironment with a high immune signature, associated with better response to IO, was present in 13% of the cases. This signature was evenly distributed among different primary sites. We found that the molecular biology for AS varies significantly according to the primary site. Our findings can facilitate the design and optimiza-tion of therapeutic strategies for AS to overcome resistance to IO and targeted therapies.

Chickens have extensive phenotypic variation. The Wuhua yellow chicken (WHYC) is an important traditional yellow-feathered chicken in China, characterized by white tail feathers, white flight feathers, and strong disease resistance. However, the genomic basis of traits associated with WHYC is still poorly understood. In this study, whole genome resequencing was performed with an average coverage of 20.77-fold to investigate heritable variation and identify selection signals in WHYC. Reads were mapped onto the chicken reference genome (Galgal5) with a coverage of 85.95%. After quality control, 11,953,471 SNPs and 1,069,574 InDels were obtained. In addition, 41,408 structural variants and 33,278 copy number variants were found. A comparative genomic analysis of WHYC and other yellow-feathered chicken showed that selected regions were enriched in genes involved in transport and catabolism, immune system, infectious diseases, signal transduction, and signaling molecules and interaction. Several genes associated with disease resistance were identified, including IFNA, IFNB, CD86, IL18, IL11RA, VEGFC, and ATG10. Furthermore, PMEL and TYRP1 may contribute to the coloring of white feathers in WHYC. These findings improve our understanding of the genetic characteristics of WHYC and may contribute to future breed improvement.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders related to aging. Though several risk factors are shared between these two diseases, the exact relationship between these two diseases is still unknown. In this paper, we analyzed how these diseases relate to each other from a genomics viewpoint. Using an extensive literature search, we accumulated the list of genes from the major genome-wide association (GWAS) studies. However, we found only one gene (HLA-DRB5) reported in these GWAS studies that are common between AD and PD. We also listed all the miRNAs that have been previously reported for AD and PD. Here we found 15 different miRNAs that were reported in both diseases. In order to get better insights, we predicted the gene coexpression network for both AD and PD. Network analysis on these networks show six clusters of genes related to AD and four clusters of genes related to PD.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Febrile seizures in early childhood can lead to developmental disorders in the CNS. However, the specific mechanisms behind the impact of febrile seizures on the developing brain are not well-understood. To address this gap in knowledge, we employed a hyperthermic model of febrile seizures in 10-day-old rats and tracked their development over two months. Our objective was to determine the degree to which the properties of the hippocampal glutamatergic system are modified. We analyzed whether pyramidal glutamatergic neurons in the hippocampus die after febrile seizures. Our findings indicate that there is a reduction in the number of neurons in various regions of the hippocampus in the first two days after seizures. The CA1 field showed the greatest susceptibility, and the reduction in the number of neurons in post-FS rats in this area appeared to be long-lasting. Electrophysiological studies indicate that febrile seizures cause a reduction in glutamatergic transmission, leading to decreased local field potential am-plitude. This impairment could be attributable to diminished glutamate release probability as evidenced by decreases in frequency of miniature excitatory postsynaptic currents and increases in pair-pulse ratio of synaptic responses. We also found higher threshold current causing hindlimb extension in the maximal electroshock seizure threshold test of rats 2 months after febrile seizures compared to control animals. Our research suggests that febrile seizures can impair glutamatergic transmission, which may protect against future seizures.

Prostate cancer is driven by acquired genetic alterations, including those impacting the epigenetic machinery. With African ancestry a significant risk factor for aggressive disease, we hypothesize that dysregulation among the roughly 656 epigenetic genes may contribute to prostate cancer health disparities. Interrogating prostate tumor genomic data from 109 men of southern African and 56 men of European Australian ancestry, we found African-derived tumors to present with a longer tail of epigenetic driver gene candidates (72 versus 10). Biased towards African-specific drivers (63 versus 9 shared), many are novel to prostate cancer (18/63) including several putative therapeutic targets (CHD7, DPF3, POLR1B, SETD1B, UBTF and VPS72). Through clustering of all variant types and copy number alterations, we describe two epigenetic PCa taxonomies capable of differentiating patients by ancestry and predicted clinical outcomes. We identified top genes in African and European-derived tumors that represent a multifunctional “generic machinery”, alteration to which may be instrumental in epigenetic dysregulation and prostate tumorigenesis. In conclusion, numerous somatic alterations in the epigenetic machinery drive prostate carcinogenesis but African-derived tumors appear to achieve this with greater diversity amongst such alterations. The greater novelty observed in African-derived tumors illustrates the significant clinical benefit to be derived from a much needed African tailored approach to prostate cancer healthcare aimed at reducing prostate cancer health disparities.

Rat is one of the most commonly used model animals for biological research. The organs and systems of human being are somewhat similar to that of rat in structure as well as functions, making it a valuable choice for research experimentation in biological sciences. A number of studies have been conducted to evaluate the potential risks and toxicity of different elements on the physiology and histology of rats. There is need to address certain environmental factors affecting rats condition during experimentation. Reproduction along with its pathologies is under investigation on larger scale throughout the world, being central for the existence of a species. These studies focus on the major factors that influence reproductive function. Review of literature clearly indicated the unwanted consequences of over nutrition, malnutrition, high or low temperature, non-enriched housing, improper handling, intense or poor light exposure and environmental pollution on histology and hormonal profile of reproductive system of rats.

The covid-19 pandemic has generated substantial changes in the lives of the population, such as increased physical inactivity, which can lead to overweight and, consequently, repercussions on glucose homeostasis. A population-based household epidemiological survey was conducted by stratified, multistage probability cluster sampling (October and December 2020) in Brazil. Participants were classified as physically active or inactive during leisure time according to the recommendations of the World Health Organization. HbA1c levels were categorized as normal (≤6.4%) or with glycemic changes (≥ 6.5%). The mediating variable was excess weight (overweight and obese). Multivariate logistic regression analyzes were performed to examine the association between physical inactivity and glycemic changes. Mediation was analyzed using the Karlson–Holm–Breen method to verify the influence of excess weight on the association. We interviewed 1,685 individuals, mostly women (52.4%), 35–59 years old (45.8%), race/ethnicity brown (48.1%), and excess weight (56.5%). The mean HbA1c was 5.68% (95% CI: 5.58-5.77). Individuals physically inactive were 2.62 times more likely to have glycemic alterations (OR:2.62.95% CI:1.29-5.33), and 26.87% of this association was mediated by excess weight (OR:1.30:95% CI:1.06-1.57). Physical inactivity in leisure time increases the chances of glycemic alterations, and part of this association can be explained by excess weight.

Microcystins (MCs) are cyanobacterial toxins and potent inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), which are involved in plant cytoskeleton (microtubules and F-actin) organization. Therefore, studies on the toxicity of cyanobacterial products on plant cells have so far being focused on MCs. In this study, we investigated the effects of extracts from 16 (4 MC-producing and 12 non-MC-producing) cyanobacterial strains from several habitats, on various enzymes (PP1, trypsin, elastase), on the plant cytoskeleton and H2O2 levels in Oryza sativa (rice) root cells. Seedling roots were treated for various time periods (1, 12 and 24h) with aqueous cyanobacterial extracts and underwent either immunostaining for α-tubulin or staining of F-actin with fluorescent phalloidin. DCF-DA staining was performed for H2O2 imaging. The enzyme assays confirmed the bioactivity of the extracts of not only MC-rich (MC+), but also MC-devoid (MC-) extracts, which induced major time-dependent alterations on both components of the plant cytoskeleton. These findings suggest that a broad spectrum of bioactive cyanobacterial compounds, apart from MCs or other known cyanotoxins (such as cylindrospermopsin), can affect plants by disrupting the cytoskeleton.

Contamination with Arsenic, a toxic metalloid, is increasing in the marine environment. Additionally, global warming can alter metalloids toxicity. Polychaetes are key species in marine environments. By mobilizing sediments, they play vital roles in nutrient and element (including contaminants) cycles. Most studies with marine invertebrates focused on the effects of metalloids on either adults or larvae. Here we bring information on the effects of temperature increase and arsenic contamination on the polychaete Hediste diversicolor in different growth stages and water temperatures. Feeding activity and biochemical responses – neurotransmission, indicators of cell damage, antioxidant and biotransformation enzymes and metabolic capacity - were evaluated. Temperature rise combined with As imposed alterations on feeding activity and biochemical endpoints at different growth stages. Small organisms have their antioxidant enzymes increased, avoiding lipid damage. However, larger organisms are the most affected class due to inhibition of superoxide dismutase, which resulted in protein damage. Oxidative damage was observed on smaller and larger organisms exposed to As and 21 °C, demonstrating higher sensibility to the combination of temperature rise and As. The observed alterations may have ecological consequences, affecting the cycle of nutrients, sediment oxygenation and the food chain that depend on the bioturbation of this polychaete.

Pathologies of the blood brain barrier (BBB) have been linked to a multitude of CNS disorders whose pathology is poorly understood. Cortical spreading depression (CSD) has long been postulated to be involved in the underlying mechanisms of these disease states, yet full understanding remains elusive. This study utilized an in vitro model of the BBB with b.End3 murine endothelial cells to investigate the role of CSD in BBB pathology by characterizing effects of the release of major pronociceptive substances on BBB functional integrity using TEER screening, transcellular uptake, and immunoreactive methods in concert with global proteome and phospho-proteomic approaches. Findings demonstrated relocalization and functional alteration to proteins associated with the cytoskeleton and endothelial tight junctions. Pathologic mechanisms induced by individual substances released during CSD were found to have unique phosphorylation signatures in phospho-proteome analysis, identifying Zona Occludens 1 as a possible pathologic “checkpoint” of the BBB. Utilizing these phosphorylation signatures, possible novel diagnostic methods may be developed for neurological diseases and warrants further investigation.

Abstract: Fanconi anemia (FA), a chromosome instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the epitome and origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.

Mandevilla (Apocynaceae) is a greatly appreciated genus in the world ornamental market. In this study, we attempted to address the poor genetic knowledge and the huge taxonomic gaps existing in this genus by analyzing the germplasm of 55 accessions. After cytometrically determining the triploid genome size (1,512.64 Mb) of a reference sample (variety “Mandevilla 2001”), the plastidial genome (cpDNA, 0,18 Mb) and a draft of the nuclear genome (nuDNA, 207 Mb) were assembled. While cpDNA was effective in reconstructing the phylogenesis of the Apocynaceae family based on a DNA superbarcoding approach, the nuDNA assembly length was found to be only 41% of the haploid genome size (506 Mb, predicted based on the K-mer frequency distribution). Its annotation enabled the prediction of thousands of genes, of which 5,275 resulted in full CDS. Among them, we identified nine genes whose orthologs (in Catharanthus roseus) encode enzymes involved in the biosynthesis of monoterpene indole alkaloids (MIAs), including catharanthine, tabersonine and vincadifformine. The nuclear genome draft was also useful to develop a highly informative (mean PIC=0.62) set of 23 SSR markers that was validated on the Mandevilla collection. These results were integrated with cytometric measurements, nuclear ITS1 haplotyping and chloroplast DNA barcoding analyses to assess the origin, divergence and relationships existing among the 55 accessions object of the study. As expected, based on the scarce information available in the literature, the scenario was extremely intricate. A reasonable hypothesis is that most of the accessions represent interspecific hybrids sharing the same species as maternal parent (i.e., Mandevilla sanderi).

Plant geneticists and breeders have used marker technology since the 1980s in quantitative trait locus (QTL) identification. Marker-assisted selection is effective for large-effect QTL but has been challenging to use with quantitative traits controlled by multiple minor effect alleles. Therefore, genomic selection (GS) was proposed to estimate all markers simultaneously, thereby capturing all their effects. However, breeding programs are still struggling to identify the best strategy to implement it into their programs. Traditional breeding programs need to be optimized to implement GS effectively. This review explores the optimization of breeding programs for variety release based on aspects of the breeder’s equation. Optimizations include reorganizing field designs, training populations, increasing the number of lines evaluated, and leveraging the large amount of genomic and phenotypic data collected across different growing seasons and environments to increase heritability estimates, selection intensity, and selection accuracy. Breeding programs can leverage their phenotypic and genotypic data to maximize genetic gain and selection accuracy through GS methods utilizing multi-trait and, multi-environment models, high-throughput phenotyping, and deep learning approaches. Overall, this review describes various methods that plant breeders can utilize to increase genetic gains and effectively implement GS in breeding .

Term vascular dysfunctional refers to a wide spectrum of vascular abnormalities including pathogenesis of tumors, their proliferation and leading to malfunctioned conditions. The treatment of most of the vascular anomalies including peripheral arterial disease and cardiac disease is multi factor procedure which include the embolic therapy, laser-based treatments and coagulation are all plating important role in managing the disease associated with vascular breakdown. The research proposal defines the treatment and diagnosis procedures involved in treatment of vascular abnormalities with a deep emphasis on techniques, efficiency and complications resulted from various other procedure and use of mapping and sequencing techniques based on genetics of variants of selected genes PIk3CA which will ultimately be more effective.

Recently the polyvalent bacteriophage FP01, isolated from wastewater in Valparaiso, Chile, was described to have lytic activity across species against Escherichia coli and Salmonella enterica serovars. Due to it polyvalent nature the bacteriophage FP01 could have potential application in food and agri-industry. Also, fundamental aspects of polyvalent bacteriophage biology are not well known. In this study we sequenced and describe the complete genome of the polyvalent phage FP01 (MH745368) using the nanopore technology. The bacteriophage FP01 genome has a 44,900 bp, double-stranded DNA with an average G+C content of 49.41% and 90 coding sequences (CDSs). We found that the phage FP01 critically depends on host factors for replication and transcription. Also, it has a critical lysogenic repressor pseudogene. Phylogenetic analyses indicated that the phage FP01 is closely related to phages lambda and P22. These results suggest that the phage FP01 could be a lytic variant of a lysogenic phage or acquired genes from lysogenic phages during host infection.

With the continuing development of sequencing technology, genomics has been applied in a variety of biological research areas. In particular, the application of genomics to marine species, which boast a high diversity, promises great scientific and industrial potential. Significant progress has been made in marine genomics especially over the past few years. Consequently, BGI, leveraging its prominent contributions in genomics research, established BGI-Qingdao, an institute specifically aimed at exploring marine genomics. In order to accelerate marine genomics research and related applications, BGI-Qingdao initiated the International Conference on Genomics of the Ocean (ICG-Ocean) to develop international collaborations and establish a focused and coherent global research plan. Last year, the first ICG-Ocean conference was held in Qingdao, China, during which 47 scientists in marine genomics from all over the world reported on their research progress to an audience of about 300 attendees. This year, we would like to build on that success, drafting a report on marine genomics to draw global attention to marine genomics. We summarized the recent progress, proposed future directions, and we would like to enable additional profound insights on marine genomics. Similar to the annual report on plant and fungal research by Kew Gardens, and the White Paper of ethical issues on experimental animals, we hope our first report on marine genomics can provide some useful insights for researchers, funding agencies as well as industry, and that future versions will expand upon the foundation established here in both breadth and depth of knowledge.This report summarizes the recent progress in marine genomics in six parts including: marine microorganisms, marine fungi, marine algae and plants, marine invertebrates, marine vertebrates and genomics-based applications.

Anthracnose, caused by the fungus Colletotrichum lindemuthianum, poses a significant and widespread threat to the common bean crop. The use of plant genetic resistance has proven to be the most effective strategy for managing anthracnose disease. The Amendoim Cavalo (AC) Andean cultivar has resistance against multiple races of C. lindemuthianum, which is conferred by the Co-AC gene. Fine mapping of this resistance gene to common bean chromosome Pv01 enabled the identification of Phvul.001G244300, Phvul.001G244400, and Phvul.001G244500 candidate genes for further validation. In this study, we assessed the relative expression of Co-AC candidate genes, as well as other putative genes in vicinity of this locus and known resistance genes, in the AC cultivar following inoculation with the race 73 of C. lindemuthianum. Gene expression analysis revealed significantly higher expression levels of Phvul.001G244500. Notably, Phvul.001G244500 encodes a putative Basic Helix-Loop-Helix transcription factor, suggesting its involvement in the regulation of defense responses. Furthermore, we observed a significant modulation of the expression of defense related genes PR1a, PR1b, and PR2, in a time-course experiment. These findings contribute to the development of improved strategies for breeding anthracnose-resistant common bean cultivars, thereby mitigating the impact of this pathogen on crop yields and ensuring sustainable bean production.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography dynamic multiple reaction monitoring targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of Chronic Myeloid Leukaemia (CML), we found that intra- and extra-cellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), and extracellular Prostaglandin F_2α (PGF_2α), 5-Hydroxyeicosatetraenoic acid (5-HETE), Palmitic acid (PA, C16:0) and Stearic acid (SA, C18:0) were altered in response to immunomodulation by type I Interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism with potential relevance in the context of cancer inflammation and CML.

Changes in food preferences after bariatric surgery may alter its effectiveness as a treatment for obesity. We aimed to compare food reward for a comprehensive variety of food categories between patients who received a sleeve gastrectomy (SG) or a Roux-en-Y gastric bypass (RYGB) and to explore whether food reward differs according to weight loss. In this cross-sectional exploratory study, food reward was assessed using the Leeds Food Preference Questionnaire (LFPQ). We assessed liking and wanting of eleven food categories. Comparisons were done regarding type of surgery and Total Weight Loss (TWL; based on tercile distribution). Fifty-six patients (30 SG and 26 RYGB) were included (women: 70%; age: 44.0 (11.1) y). Regarding the type of surgery, scores were not significantly different between SG and RYGB, except for ‘non-dairy products – without color’ explicit liking (p = 0.04). Regarding TWL outcomes, explicit liking, explicit wanting and implicit wanting, scores were significantly higher for Good responders than Low responders for ‘No meat – High fat’ (post-hoc corrected p-value: 0.04, 0.03 and 0.04, respectively). Together, our results failed to identify major differences in liking and wanting regarding the type of surgery and tended to indicate that higher weight loss might be related to a higher reward for high protein-content food. Rather to focus only on palatable foods, future studies should also consider a broader range of food items, including protein reward.

This comprehensive review traces the transformative journey of genomic mapping, ushering in the era of "Genomic Atlas 2.0," characterized by advanced strategies and cutting-edge technologies. Beginning with a historical overview, it highlights the evolution from early linkage analysis to the current landscape shaped by high-throughput sequencing. Key breakthroughs are emphasized, showcasing the pivotal role of platforms such as Illumina and Oxford Nanopore in accelerating the identification of genetic variations. Long-read sequencing technologies, including PacBio and Oxford Nanopore, are explored as transformative elements overcoming limitations associated with short-read sequencing. The review delves into spatial genomics and chromatin conformation capture techniques, revealing the three-dimensional intricacies of the genome, with a particular focus on the revolutionary impact of Hi-C in understanding chromatin interactions. CRISPR technologies emerge as indispensable tools in Genomic Atlas 2.0, enabling targeted genome editing and the generation of precise genetic models. Functional genomics screens, utilizing RNA interference and CRISPR-based techniques, are discussed for their scalable precision in deciphering genome functions. Navigating challenges, the review addresses complexities in data integration and ethical considerations, offering strategies to ensure the robustness and ethical conduct of genetic mapping. Looking optimistically towards the future, it explores opportunities such as improved sequencing accuracy and novel applications of CRISPR technologies. Envisioning the expansion of genomics into personalized medicine, agriculture, and conservation biology, the review serves as a guiding resource for researchers, scientists, and students navigating the intricate terrain of Genomic Atlas 2.0.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as the current coronavirus pandemic is an infectious disease that initially confirmed in China in late December 2019. In this study, we analyzed 131 complete sequences of SARS-CoV-2 from Asia. Our results show that there are fifteen major mutations in Asia which most of them are co-evolved. There were five groups based on co-mutations which three of them resulted in clade G including (241C>T, 3037C>T, 14408C>T, and 23403A>G), (28881G>A, 28882G>A, 28883G>C and 23403A>G) and (25563G>T and 23403A>G). Co-mutations in (8782C>T and 28144T>C) and (1397G>A, 28688T>C, 29742G>T and 11083G>T) were clustered in clade S and a new clade outside of GISAID classification, respectively. Sequences with a mutation in 26144G>T had low variability without any co-mutation which formed clade V. In this study, we showed that Most of the circulated viruses in Asia collected in five co-mutation groups which may affect the transmissibility and vaccine designing strategies.

The MLL1 gene located on chromosome 11q23, is crucial for histone lysine-specific methylation and is frequently implicated in various leukemia types. Despite prior in silico investigations into non-synonymous single nucleotide polymorphisms (nsSNPs) associated with leukemia in the MLL1 gene, there is a dearth of comprehensive studies evaluating their impact on the protein's structure, function, and post-translational modifications. Addressing this, our study screened 2049 nsSNPs from the dbSNP database, identifying 62 high-risk variants. A thorough domain analysis revealed that these nsSNPs are distributed across seven domains of the MLL1 protein, potentially affecting their functions. Our conservation analysis highlighted 31 nsSNPs as deleterious, suggesting their potential effects on protein stability and function. Furthermore, utilizing the MutPred2 tool, we identified mutations affecting metal-binding, protein loop structures, and post-translational modifications, which could alter the MLL1 protein's native functionality. Interaction network analysis underscored the role of MLL1 in hematopoietic cell development, implying that mutations may influence hematological malignancies. Additionally, a subset of non-coding SNPs was found to possess regulatory capabilities, potentially affecting gene expression and chromatin modification. Most significantly, using CScape and CScape-somatic tools, four nsSNPs were predicted to be oncogenic, with two classified as cancer drivers, underscoring their potential role in leukemia development. The oncogenic nsSNP, D2724G, located between the FY-rich N and FY-rich C domain of the MLL1 protein, has raised significant interest due to its potential impact on proteolytic cleavage. Predictive analyses, such as those by Mutpred2, suggest a loss of cleavage at D2724 caused by this mutation, potentially affecting the formation of essential MLL1 fragments, p320 and p180. These fragments play a crucial role in creating a stable multiprotein complex that localizes to a specific subnuclear region. Therefore, mutations like D2724G can potentially alter gene expression patterns, influencing cellular behavior and possibly fostering a cancer-prone environment. In conclusion, our research provides an in-depth assessment of the effects of nsSNPs in the MLL1 gene on leukemia, offering potential avenues for personalized treatment strategies, early detection, prognosis, and a better understanding of hematological malignancy genesis.

Background: high-altitude work exposes individuals to reduced oxygen levels, imposing physi-ological adaptations. These conditions can induce alterations in the cardiovascular system, po-tentially exacerbating pre-existing health issues and impacting overall well-being of workers in such environments. This study has investigated the cardiovascular challenges for the high-altitude worker on Etna volcano. Methods: Through an observational study, ten healthy, non-smoking male participants underwent cardiovascular and pulmonary function tests at alti-tudes below 500m and above 3000m, simulating work conditions on the volcano. Results: signif-icant findings include elevated systemic blood pressure and heart rate, indicating an increased cardiovascular workload necessary for adaptation to hypoxia. Conclusions: the study highlights the importance of acclimatization to high altitude for minimizing cardiovascular risks among workers. It calls for the development of safety protocols, underlining the critical role of preven-tative measures and specific safety protocols for high-altitude workers.

Dendritic spines are essential for synaptic function because they constitute the neurons' postsynaptic compartment that receives the most excitatory input. The extracellularly shorter variant of the presynaptic cell adhesion molecules neurexins, β-neurexins, has been implicated in various aspects of synapse function including neurotransmitter release. However, its role in developing or stabilizing dendritic spines as fundamental computational units of excitatory synapses remained unclear. Here, we show by morphological analysis that the deletion of β-neurexins in hippocampal neurons in vitro and in hippocampal tissue in vivo affects presynaptic dense-core vesicles and, unexpectedly, postsynaptic spine structure. Specifically, we observed that the absence of β-neurexins led to an increase in longer spinous protrusions in vitro and more mature mushroom-type spines in the CA1 region of adult knockout mice. In addition, deletion of β-neurexins caused alterations in spine head dimension and more spines with perforations of their postsynaptic density but no change in the overall number of spines or synapses. Our results indicate that presynaptic β-neurexins play a role across the synaptic cleft, possibly by aligning with postsynaptic binding partners and glutamate receptors via transsynaptic columns.

Rabies is a fatal zoonosis that is considered a re-emerging infectious disease. Although rabies remains endemic in canines throughout much of the world, vaccination programs have essentially eliminated dog rabies in the Americas and much of Europe. However, despite the goal of eradicating dog rabies in the European Union by 2020, sporadic cases of dog rabies still occur in Eastern Europe, including Georgia. To assess the genetic diversity of strains recently circulating in Georgia, we sequenced 78 RABV-positive samples from brain tissues of rabid dogs and jackals using Illumina short-read sequencing of total RNA shotgun libraries. Seventy-seven RABV genomes were successfully assembled and annotated, 74 of them to the coding complete status. Phylogenetic analyses of the nucleoprotein (N) and attachment glycoprotein (G) genes placed all the assembled genomes into the Cosmopolitan clade, consistent with the Georgian origin of the samples. Amino acid alignment of the G glycoprotein ectodomain identified twelve different sequences for this domain among the samples. Only one of the ectodomain groups contained a residue change in an antigenic site, an R264H change in the G5 antigenic site. Three isolates were cultured, and these were found to be efficiently neutralized by human monoclonal antibody A6. Overall, our data show that recently circulating RABV isolates from Georgian canines are predominantly closely related phylogroup I viruses of the Cosmopolitan clade. Current rabies vaccines should offer protection against infection by Georgian canine RABVs. The genomes have been deposited in GenBank (accessions: OQ603609-OQ603685).

Sheep (Ovis aries) provide a vital source of protein and fibre to human populations. In coming decades, as the pressures associated with rapidly changing climates increase, breeding sheep sustainably as well as producing enough protein to feed a growing human population will pose a considerable challenge for sheep production across the globe. High quality reference genomes and other genomic resources can help to meet these challenges by: 1) informing breeding programmes by adding a priori information about the genome, 2) providing tools such as pangenomes for characterising and conserving genetic diversity, and 3) improving our understanding of fundamental biology using the power of genomic information to link cell, tissue and whole animal scale knowledge. In this review we describe recent advances in the genomic resources available for sheep, discuss how these might help to meet future challenges for sheep production, and provide some insight into what the future might hold.

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

Genomic selection (GS) is a predictive approach that was build up to increase the rate of genetic gain per unit of time in breeding programs. It has emerged as a valuable method for improving complex traits that are controlled by many genes with small effect. GS enables the prediction of breeding value of candidate genotypes for selection. In this work we address important issues related to GS and its implementation in tomato breeding context. Genomic constrains and critical parameters affecting the accuracy of prediction in such crop such as phenotyping, genotyping training population composition and size and statistical method should be carefully evaluated. Comparison of GS approaches for facilitating the selection of tomato superior genotypes during breeding program are also discussed. GS applied to tomato breeding has already shown to be feasible. We illustrated how GS can improve the rate of gain in elite lines selection, descendent and in backcross schemes. The GS schemes begin to be delineated and computer science can provide support for future selection strategies. A new breeding framework is beginning to emerge for optimizing tomato improvement procedures.

In the recent past, there has been a rise in Prostate Cancer (PCa) in Asia, particularly India. Although systematic reviews on PCa have dealt on the genetics, genomics and the environmental influence in causal of PCa, no predictive analytics in comparing the PCa from Caucasian, American to Asian population was attempted. In this review article, we have attempted to elaborate this aspect of PCa and deliberated on challenges related to next generation sequencing methods of PCa’s manifestation when compared to the west.

Cryptosporidiosis is a widespread disease caused by the parasitic protozoan Cryptosporidium spp., which infects various vertebrate species, including humans. Once unknown as a gastroenteritis-causing agent, Cryptosporidium spp. is now recognized as a pathogen causing life-threatening disease, especially in immunocompromised individuals such as AIDS patients. Advances in diagnostic methods and increased awareness have led to a significant shift in the perception of Cryptosporidium spp. as a pathogen. Nowadays, genomic and proteomic studies have played a main role in understanding the molecular biology of this complex-life-cycle parasite. Genomics has enabled the identification of numerous genes involved in the parasite's development and interaction with hosts. Proteomics has allowed for the identification of protein interactions, their function, structure, and cellular activity. The combination of these two approaches has significantly contributed to the development of new diagnostic tools, vaccines, and drugs for cryptosporidiosis. In this review, we summarize the major accomplishments in the field of Cryptosporidium research using genomics and proteomics.

Fibroepithelial lesions (FL) of the breast, in particular Phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT, and FA. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors. We compiled a series of patient-derived archival biopsy specimens reflecting the FL spectrum and histological mimickers including clinical follow-up data. DNA methylation and CNVs were determined by well-established microarrays. Comparison of the patterns with a pan-cancer dataset assembled from public resources including "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) suggests that FLs form a methylation class distinct from both control breast tissue as well as common breast cancers. Complex CNVs were enriched in clinically aggressive FLs. Subsequent fluorescence in situ hybridization (FISH) analysis detected respective aberrations in the neoplastic mesenchymal component of FLs only, confirming that the epithelial component is non-neoplastic. Of note, our approach could lead to the elimination of the diagnostically problematic category of borderline PT and allow for optimized prognostic patient stratification. Furthermore, the identified recurrent genomic aberrations such as 1q gains (including MDM4), CDKN2a/b deletions and EGFR amplifications may inform therapeutic decision-making.

COVID-19 pandemic in first seven months has led to more than 15 million confirmed infected cases and 600,000 deaths. SARS-CoV-2, the causative agent for COVID-19 has proved a great challenge for its ability to spread in asymptomatic stages and a diverse disease spectrum it has generated. This has created a challenge of unimaginable magnitude not only affecting human health and life but also potentially generating a long-lasting socioeconomic impact. Both medical sciences and biomedical research have also been challenged consequently leading to a large number of clinical trials and vaccine initiatives. While known proteins of pathobiological importance are targets for these therapeutic approaches, it is imperative to explore other factors of viral significance. Accessory proteins are one such trait that have diverse roles in coronavirus pathobiology. Here we analyze certain genomic characteristics of SARS-CoV-2 accessory protein ORF8, predict upon its protein features and review current available literature regarding its function. We have also undertaken review of ORF8 homolog ORF8ab from SARS-CoV with a purpose of developing holistic understanding of these proteins for reason that coronaviruses have been infecting humans repeatedly and might continue to do so. Despite low nucleotide and protein identity and differentiating genome level characteristics, there appears to be significant structural integrity and functional proximity between these proteins pointing towards their high significance. There is further need for comprehensive genomics and structural-functional studies to lead towards definitive conclusions regarding their criticality and that can eventually define their relevance to therapeutics development.

Background: Proteins targeted by the Ubiquitin Proteasome System (UPS) are identified for degradation by the proteasome, which has been implicated in the development of neuro-degenerative diseases. Major histocompatibility complex (MHC) molecules present peptides broken down by the proteasome and are involved in neuronal plasticity, regulating synapse number and axon regeneration in the central or peripheral nervous system during develop-ment and in brain diseases. The mechanisms governing these effects are mostly unknown, but evidence from different compartments of the cerebral cortex indicates the presence of im-mune-like MHC receptors in the central nervous system. Methods: We have used human induced pluripotent stem cells (iPSC) differentiated to neural stem cells and then to motor neurons as a developmental model to better understand the structure of the proteasome in developing motor neurons. We perform a proteomic analysis of starting human skin fibroblasts, their matching iPSC, differentiated neural stem cells and motor neurons that highlighted significant differences in the constitutive proteasome and immunoproteasome subunits during development towards motor neurons from iPSC. Results: Proteomic analysis showed that the catalytic proteasome subunits expressed in fi-broblasts differ to those in neural stem cells and motor neurons. Western blot analysis con-firmed the proteomic data, particularly the decreased expression of Beta5i (PSMB8) subunit immunoproteasome. Conclusion: The constitutive proteasome subunits are upregulated in iPSC from HFF and the immunoproteasome subunit beta 5i expression is higher in MN than NSC suggesting a im-munoproteasome phenotype in MN. The immunoproteasome may have implications on motor neuron development and neurodevelopmental diseases that warrants further investi-gation.

Environmental factors as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. The epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol HFD+RV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RV groups and their offspring. Molecularly, a significant increase in 5-mC levels, as well as increased gene expression of Dnmt1 and Dnmt3a in HFD+RV F1 group, were found. Furthermore, a significantly increased of m6A levels in HFD+RV F1 were found, and there were changes in gene expression of its enzymes (Mettl3 and Fto). Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as Il1-β, Il-6, Tnf-α, Cxcl-10, Mcp-1 and Tgf-β1 in HFD+RV and HFD+RV F1 groups. Moreover, there was increased gene expression of neurotrophins such as Ngf and Nt3 and its receptors TrkA and TrkB. Likewise, an increase in protein levels of BDNF and p-Akt in HFD+RV F1 was found. These results suggest that maternal RV supplementation under HFD intake prevents cognitive decline in SAMP8 adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, restoring the epigenetic landscape as well as synaptic plasticity.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

Significant changes have occurred at Arabian Gulf Coast of Saudi Arabia over the last three decades. The area of mangrove was reduced by about 55%. Thus the economic, social, and environmental value of mangroves must be assessed over short -to long-term scales and employ these assessments for the awareness rising at local communities. This study provides a preliminary assessment of the risks on mangrove vegetation; it will provide database to mitigate the tremendous pressures due to coastal development and urban activities. The effects of human development on the mangrove plant cover in Eastern Region of KSA were recognised, during 2013 to 2016. The mean variations of physio-chemical characteristics in water and sediment were recorded. With regard to water analyses including; nitrogen, phosphorus, TSS, TDS, BOD, and turbidity were evaluated. On the other hand, for sediment: TDS, nitrogen, phosphorus, sulphate and total organic carbon were assessed. Moreover, the growth parameters: plant height, and size index, of Avicennia marina were recorded and estimated. It is concluded that human impact and urban developments have exerted drastic effects on the coastal ecosystems and its environments.

Background. Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. Patients and Methods. To identify them, a retrospective observational study was carried out selecting patients without palpable tumour, without axillary involvement, and a genomic analysis was performed with PAM50. Results. The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90-0.93) at 20 years and 0.96 (95% CI, 0.92-1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumours and in 9 (9.47%) luminal B tumours smaller than 1 cm and in HER2 and basal type tumours there were no metastatic events (20-year DMFI of 1.00). Conclusion. Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumour size less than 1 cm. De-escalation of treatment should be considered.

Streptomyces sp. HNS054, which was previously isolated from a marine sponge, demonstrates vigorous growth and facile genetic modification. This study explores its potential as a marine ac-tinomycete chassis through complete genome sequencing and genetic engineering. With a 7.5 Mb genome containing 6678 predicted genes, 21 secondary metabolic biosynthetic gene clusters (BGCs), and 8 common site-specific recombination (SSR) system attB loci, HNS054 shows a close phylogenetic relation to S. griseoincarnatus strain RB7AG. Utilizing multiplexed site-specific ge-nome engineering (MSGE) and the CRISPR/Cas9 method, engineered strains derived from HNS054 (with three copies of the target BGCs) produce higher amounts of aborycin and ac-tinorhodin than S. coelicolor M1346 (containing three copies of the same BGCs). HNS054 stands out for its remarkable characteristics, including salt tolerance, rapid growth, and compatibility with synthetic biology tools, and positions it as a promising candidate for developing marine ac-tinomycete hosts to enhance secondary metabolite production.

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.

Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its copy number alteration (CNA) and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2 and 12p13.31 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.

This study assessed the impact of inoculation with plant growth-promoting bacteria (PGPB) on stress-resistance and growth-promoting metabolites in Salicornia europaea L. across controlled and field conditions. Salicornia europaea seeds, inoculated with Brevibacterium casei EB3 and Pseudomonas oryzihabitans RL18, were grown in controlled laboratory experiments and in a nat-ural field setting. Metabolite composition was analyzed using GC-MS and UHPLC-MS. Under controlled conditions, PGPB inoculation significantly increased levels of unsaturated fatty acids, sugars, citric acid, acetic acid, chlorogenic acids, and quercetin. Inoculation under field condi-tions increased glucose, fructose, quercetin, and apigenin, alongside decreased unsaturated fatty acids and sterols, indicating a stress response shift in plant metabolism. Under controlled condi-tions, enhanced metabolite profiles induced by inoculation likely contributed to augmented bio-mass production and environmental stress resistance. Field plants revealed distinct phytochemi-cal profiles, suggesting higher stress levels. However, the accumulated metabolites from inocula-tion could enhance the plant's ability to cope with adverse conditions and improving stress tol-erance. This study unveils the intricate metabolic adaptations of Salicornia europaea under con-trolled and field stress conditions, highlighting PGPB's potential to enhance plant stress tolerance. Elevated stress-related metabolites may fortify plant defense mechanisms, laying the ground-work for stress-resistant crop development through PGPB-based inoculants, especially in saline agriculture.

Epigenetic alterations are heritable and enduring modifications in gene expression that play a pivotal role in immune evasion. These include alterations to noncoding RNA, DNA methylation, and histone modifications. DNA methylation plays a crucial role in normal cell growth and development but alterations in methylation patterns such as hypermethylation or hypomethylation can enable tumor and viral cells to evade host immune responses. Histone modifications can also inhibit immune responses by promoting the expression of genes involved in suppressing normal immune function. In the case of T-cell lymphoma, adult T-cell Lymphomas (ALT) also undergo immune evasion through the exceptional function of its accessory and regulatory genes. Epigenetic therapies are emerging as a promising adjunct to traditional immunotherapy and chemotherapy regimens. Clinical trials are currently investigating the use of epigenetic therapies in combination with immunotherapies and chemotherapies for more effective treatment of ATL and other cancers. This review highlights epigenetic alterations that are widely found in T cell malignancies.

An increasing amount of evidence indicates the critical role of the cutaneous nervous system in the initiation and maintenance of psoriatic skin lesions by neurogenic inflammation. However, molecular mechanisms affecting cutaneous neurons are largely uncharacterized. Therefore, we reanalyzed a psoriatic RNA sequencing dataset from published transcriptome experiments of nearly 300 individuals. Using the Ingenuity Pathway Analysis software, we associated several hundreds of differentially expressed transcripts (DETs) to nervous system development and functions. Since neuronal projections were previously reported to be affected in psoriasis, we performed an in-depth analysis of neurite formation-related processed. Our in silico analysis suggests that SEMA-PLXN and ROBO-DCC-UNC5 regulating axonal growth and repulsion are differentially affected in non-lesional and lesional skin samples. We identified opposing expressional alterations in secreted ligands for axonal guidance signaling (RTN4/NOGOA, NTNs, SEMAs, SLITs) and non-conventional axon guidance regulating ligands, including WNT5A and their receptors, modulating axon formation. These differences in neuritogenesis may explain the abnormal cutaneous nerve filament formation described in psoriatic skin. The processes also influence T cell activation and infiltration, thus highlighting an additional angle of the crosstalk between the cutaneous nervous system and the immune responses in psoriasis pathogenesis, in addition to the known neurogenic pro-inflammatory mediators.

Background: Protein CCDC186 is involved in the maturation of dense core vesicles in the trans-Golgi network in neurons and endocrine cells. To date, only one patient, within a large sequencing study of 1000 cases, and a single case report with variants in CCDC186 had previously been described. However, no functional studies in any of these two cases had been performed. Methods: Exome sequencing from one affected individual of each family was performed. In addition, Sanger sequencing of the parents and one of the affected siblings was also performed. CCDC186 protein was assessed in cultured fibroblasts or muscle tissue by western blot. Transcriptomic analysis was done by means of RNA sequencing. Results. We identified three patients from two gypsy families, unrelated to each other, with the same homozygous mutations in CCDC186 gene. Clinically, all patients presented with seizures, frontotemporal atrophy, hypomyelination, recurrent infections, and endocrine disturbances such as severe non ketotic hypoglycemia. Low levels of cortisol, insulin or growth hormone could only be verified in one patient. All of them had a neonatal onset and died between 7 months and 4 years of age. WES identified a homozygous variant in CCDC186 gene (c.2215C>T, p.Arg739Ter) in the index patients of both families. Protein expression studies demonstrated that the CCDC186 was practically undetectable in fibroblasts and muscle tissue. These observations correlated perfectly with the transcriptomic analysis performed in fibroblasts in one of the patients, which showed a significant reduction of CCDC186 mRNA levels. Conclusion. Our study provides functional evidence that mutations in this gene have a pathogenic effect on the protein and reinforces CCDC186 as a new disease-associated gene. In addition, mutations in CCDC186 could explain the combined endocrine and neurologic alterations detected in our patients

Recent studies show that repetitive transcranial magnetic stimulation (rTMS) improves cognitive and motor functions in patients with Parkinson’s Disease (PD). Gamma rhythm low-field magnetic stimulation (LFMS) is a new non-invasive rTMS technique that generates diffused and low-intensity magnetic stimulation to deep cortical and subcortical areas. To investigate potential therapeutic effects of LFMS in PD, we subjected an experimental mouse model to LFMS (as early treatment). We examined the LFMS effect on motor functions as well as neuronal and glial activities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced male C57BL/6J mice. Mice received MPTP injection (30 mg/kg, i.p., once daily for 5 days) followed by LFMS treatment, 20 minutes each day for 7 days. LFMS treatment improved motor functions compared to the sham-treated MPTP mice. Further, LFMS significantly improved tyrosine hydroxylase (TH) and decreased glial fibrillary acidic protein (GFAP) levels, in substantia nigra pars compacta (SNpc) and non- significantly in striatal (ST) regions. LFMS treatment improved neuronal nuclei (NeuN) level in SNpc. Our findings suggest that early LFMS treatment improved the neuron survival and in turn, motor functions in MPTP intoxicated mice brain. Further investigation is required to clearly define the molecular mechanisms by which LFMS improves motor and cognitive function in PD patients.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep-wake cycle, locomotion and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep-wake cycle of rats increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin-A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin-A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons which may be responsible for alterations of the sleep-wake cycle.

A novel coronavirus COVID-19 was first emerged in Wuhan city of Hubei Province in China in December 2019. The COVID-19, since then spreads to 213 countries and territories, and has become a pandemic. Genomic analyses have indicated that the virus, popularly named as corona, originated through a natural process and is probably not a purposefully manipulated laboratory construct. However, currently available data are not sufficient to precisely conclude the origin of this fearsome virus. Genome-wide annotation of thousands of genomes revealed that more than 1,407 nucleotide mutations and 722 amino acids replacements occurred at different positions of the SARS-CoV-2. The spike (S) glycoprotein of SARS-CoV-2 possesses a functional polybasic (furin) cleavage site at the S1-S2 boundary through the insertion of 12 nucleotides. It leads to the predicted acquisition of 3-O-linked glycan around the cleavage site. Although real-time RT-PCR methods targeting specific gene(s) have widely been used to diagnose the COVID-19 patients, however, recently developed more convenient, rapid, and specific diagnostic tools targeting IgM/IgG or newly developed plug and play methods should be available for resource-poor developing countries. Some drugs, vaccines and therapies have shown great promise in early trials, however, these candidates of preventive or therapeutic agents have to pass a long path of trials before being released for the practical application against COVID-19. This review updates current knowledge on origin, genomic evolution, development of the diagnostic tools and the preventive or therapeutic remedies of the COVID-19, and discusses on scopes for further research and effective management and surveillance of COVID-19.

A rare genetic disorder caused by col18.a1 mutations, inherited mostly in autosomal recessive and rarely in autosomal dominant pattern, giving rise to ocular abnormalities and other associated disorders, the condition is referred to as Knobloch syndrome. This paper overviews the anterior and posterior ocular symptoms in Knobloch patients, thus demonstrating the major findings in Knobloch cases including the mutational analysis which discusses the proteins involved and exon number on which mutations are detected. Animal modeling done by knocking out col18.a1 has also been discussed to determine the functions of this gene which have been identified based on anomalies found in knock-out mice.

The COVID-19 pandemic caused by the RNA virus SARS-CoV-2, has had a significant impact not only on bodily metabolism but also at the genomic level. This study utilizes a bibliometric approach to map and identify the relationship between COVID-19 and DNA damage, genomic instability, and cell cycle deregulation. The research began with the development of in-depth research questions and conducted two rounds of literature search in the Scopus database with stringent filters to ensure relevance and accuracy. From an initial 1098 documents, 576 relevant documents were selected for further analysis. The collected data was then visualized using bibliometric methods, enabling the identification of important patterns, trends, and relationships among the research variables. Key findings indicate that DNA damage, which can induce apoptosis, is the worst impact of the infection on cells. Term frequency analysis and science mapping revealed a close relationship between "DNA damage" and "apoptosis". Furthermore, discussions on genomic instability highlight telomere regulation issues, while cell cycle deregulation during virus replication in mammalian cells indicates the importance of maintaining cell membrane integrity.This study confirms the importance of bibliometric analysis in detecting and understanding the impact of COVID-19 at the genomic level, proposing several potential research targets and enhancing our understanding of the biological response to viral infection.

Background: Human papillomavirus (HPV) infection plays a key role in the development of cervical cancer that ranks as the third most common gynecological cancer in China. We attempt to investigate the age and genotype-specific prevalence of HPV DNA in western Chinese females. Methods: A total of 301,880 woman were recruited from 4 different regions of western China. Routine cervical samples were collected and HPV screening was performed using 21 HPV Genotyping test (Hybribio). The overall prevalence, age-specific prevalence, and genotype distribution were analyzed. Results: The overall prevalence of HPV was 18.01%. The high-risk HPV infection rate was 79.14%, the low-risk HPV infection rate was 12.56%, and the mixed HPV infection rate was 8.30%. The most common 4 HR HPV subtypes were HPV-52, 16, 58 and 53, which accounted for 20.49 %, 19.93 %, 14.54 % and 10.01 %. In LR HPV genotype, HPV-6 ranked the highest (28.17 %), followed by HPV-81 (9.09 %), HPV-11 (3.78 %). HPV genotype subgroup analysis also showed that single-type infections had the highest prevalence rate (77.26%) among HPV positive individuals. Among muti-infection genotype, double infection was most common with frequencies of 76.04%. Conclusion: This large report shows that the overall prevalence of HPV was high in China, whose distribution exhibits different patterns across different particular age and regions. Viral genotypes HPV53, 6 were are frequently detected in this population, which is worth of significant clinical attention.

In 2020, the pandemic caused by the Coronaviruses (CoV) that are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV2). The Coronavirus disease (COVID-19) is a new strain that was discovered in 2019 and has not been previously identified in humans. It is the high time to investigate the quantitative and/or qualitative genomic informations of the virus SARS-CoV2 in order to strengthen the healthcare facility to fight against this viral disease. In this article, a through quantitative understanding of the purine and pyrimidine spatial distribution/organization of all 89 complete sequences of SARS-CoV (available as on date in the NCBI virus database, is made using different parameters such as fractal dimension, Hurst exponent, Shannon entropy and GC content of the nucleotide sequences of the genome of SARS-CoV2. Also a cluster among all the the SARS-CoV sequences of nucleotide have been made based on their phylogeny made through their closeness (Hamming distance) based on respective purine-pyrimidine distribution.

Pasmo (Septoria linicola) is a fungal disease causing major losses in seed yield and quality, and stem fibre quality in flax. Pasmo resistance (PR) is quantitative and has low heritability. To improve PR breeding efficiency, the accuracy of genomic prediction (GP) was evaluated using a diverse worldwide core collection of 370 accessions. Four marker sets, including three defined by 500, 134, and 67 previously identified quantitative trait loci (QTL) and one of 52,347 PR-correlated genome-wide single nucleotide polymorphisms, were used to build ridge regression best linear unbiased prediction (RR-BLUP) models using pasmo severity (PS) data collected from field experiments performed during five consecutive years. With five-fold random cross-validation, GP accuracy as high as 0.92 was obtained from the models using the 500 QTL when the average PS was used as the training dataset. GP accuracy increased with training population size, reaching values >0.9 with training population size greater than 185. Linear regression of the observed PS with the number of positive-effect QTL in accessions provided an alternative GP approach with an accuracy of 0.86. The results demonstrate the GP models based on marker information from all identified QTL and the 5-year PS average is highly effective for PR prediction.

The genetic causes of the differentiated, highly treatable and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully known. The widely accepted PTC etiology blames altered sequence or/and expression level of certain biomarker genes. However, our previous studies found that the PTC biomarkers played significantly lower roles than the personalized PTC Gene Master Regulators. Our publicly accessible gene expression data from the cancer nodule and the surrounding normal tissue of surgically removed PTC tumor were re-analyzed to determine the transcriptomic effects on the genomic fabrics responsible for the DNA replication, repair and transcription. Tumor results were compared to the gene expression profiles of the papillary (BCPAP) and the anaplastic (8505C) human thyroid cancer cell lines. The analyses were carried out from the Genomic Fabric Paradigm (GFP) perspective that provides the most theoretically possible comprehensive characterization of the transcriptome and its alterations in disease. The study indicated that, in addition to regulating numerous genes, changes in the homeostatic control of transcript abundances and remodeling of the gene networks had major contributions to the PTC occurrence, resilience and proliferation. Therefore, the molecular mechanisms responsible for gene expression control and inter-coordination should also be considered when designing personalized anti-cancer gene therapies.

Recent dramatic reductions in the timeframe in which genomic sequencing can deliver results means its application in time-sensitive screening programs such as newborn screening (NBS) is becoming a reality. As genomic NBS (gNBS) programs are developed around the world, there is an increasing need to address the ethical and social issues that such initiatives raise. This study therefore aimed to explore the Australian public’s perspectives and values regarding key gNBS characteristics and preferences for service delivery. We recruited English-speaking members of the Australian public over 18 years of age via social media; 75 people aged 23-72 participated in one of 15 focus groups. Participants were generally supportive of introducing genomic sequencing into newborn screening, with several stating that adoption of such revolutionary and beneficial technology was a moral obligation. Participants consistently highlighted receiving an early diagnosis as the leading benefit, which was frequently linked to the potential for early treatment and intervention, or access to other forms of assistance, such as peer support. Informing parents about the test during pregnancy was considered important. This study provides insights into the Australian public’s views and preferences to inform the delivery of a gNBS program in the Australian context.

The unusual occurrence and developmental diversity of asexual eukaryotes still remain a puzzle. Despite asexual organisms have a theorized two-fold reproductive advantage over sexuals, asexual lineages are rare among multicellular eukaryotes. Justification of such disparity relies on the consequences of a lack of meiosis, which restricts genotype diversity and adaptation to novel conditions while accelerating the genetic degeneration that drives asexual lineages to an early demise. However, evidence indicates asexuals use different strategies to limit negative consequences of ameiosis, and age estimates show some asexual vertebrates and plants are much older than expected. If rapid extinction is not a factor influencing asexuals lifespan, then why asexuals are not more frequent? Here we review traditional ideas and new data and provide a novel unified evolutionary frame to understand the intriguing nature, developmental diversity and maintenance of asexual lineages. As a rule, de novo formation of a functioning asexual genome requires a unique assemblage combining particular sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and affect discrete components of sexuality to produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, i.e. a non-recombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.