Miracle-dz/UniFAR-FTUs huggingface dataset:
Podosomes in endothelial cell-microenvironment interactions.

PURPOSE OF REVIEW The discovery of podosomes in endothelial cells during the process of angiogenesis in vivo opens a new era in vascular biology. Podosomes are actin-based microdomains located at the plasma membrane that have been extensively described but in vitro and in other cells. This review focuses on podosomes in endothelial cells and aims to rise hypotheses about when and how these structures mediate cell--microenvironment interactions. RECENT FINDINGS A wealth of new information regarding podosome organization and functioning has been collected in simple 2D models. Characterization of their modular architecture has unravelled their mechanics. However, context matters and podosome characteristics and functioning are shaped by the microenvironment. Although matrix degradation was seen as the typical function of podosomes, mechanosensing now appears equally prominent and involved in setting of the proteolytic machinery. Endothelial podosomes breach the basement membrane, and are thus, involved in vascular remodelling. SUMMARY In endothelial cells, podosomes are involved in breaking up the basement membrane, giving the cells the opportunity to invade adjacent tissues and to engage in new cell--cell interactions. Such functions are particularly relevant to vascular biology and the exploration of podosomes in in vivo settings should bring clues to many unanswered questions.
GADMA: Genetic algorithm for inferring demographic history of multiple populations from allele frequency spectrum data

During the last few years more and more genomic analysis of individuals of closely related species has appeared. The history of evolution and development of populations, so-called demographic history, is embedded into their genome and we can try to pull it out. Allele frequency spectrum or AFS, the distribution of allele frequency in populations, is a popular and convenient representation of the genetic information. The AFS is used to build evolution of multiple populations and there are some methods to do it, for example, well-known software ∂a∂i or recently appeared moments. Both of them provide an opportunity to simulate AFS from any specified by researcher demographic model and to fit the best-likelihood parameters using local optimizations. However there is no known global search algorithms for demographic model inferring with given AFS. We introduce here a new method of automatic unsupervised inferring of the demographic model from the allele frequency spectrum. It is based on genetic algorithm — one of the most effective algorithms for global search. Our method was implemented in software GADMA (Genetic Algorithm for Demographic Analysis, https://github.com/ctlab/GADMA) and showed itself rather efficient: it automatically finds close or even better demographic model than the one that were previously received manually. Moreover it shows different local optima close to global one, so it is possible to find more biology corrected model during further research. Our approach confirm existing history of modern people and find some new demographic models for the history of butterfly E. gillettii.
Anti-pituitary and anti-hypothalamus autoantibody associations with inflammation and hypogonadotropic hypogonadism in men with traumatic brain injury.

Traumatic brain injury (TBI) and can lead to persistent hypogonadotropic hypogonadism (PHH) and poor outcomes. We hypothesized that autoimmune and inflammatory mechanisms contribute to PHH pathogenesis. Men with moderate-to-severe TBI (n=143) were compared to healthy men (n=39). The TBI group provided blood samples 1-12 months post-injury (N=1225). TBI and healthy control (n=39) samples were assayed for testosterone (T) and luteinizing hormone (LH) to adjudicate PHH status. TBI samples 1-6 months post injury and control samples were assayed for immunoglobulin M (IgM)/immunoglobulin (IgG) anti-pituitary autoantibodies (APA) and anti-hypothalamus autoantibodies (AHA). Tissue antigen specificity for APA and AHA was confirmed via immunohistochemistry (IHC). IgM and IgG autoantibodies for glial fibrillary acid protein (GFAP) (AGA) were evaluated to gauge APA and AHA production as a generalized autoimmune response to TBI and to evaluate the specificity of APA and AHA to PHH status. An inflammatory marker panel was used to assess relationships to autoantibody profiles and PHH status. Fifty-one men with TBI (36%) had PHH. An age-related decline in T levels by both TBI and PHH status were observed. Injured men had higher APA IgM, APA IgG, AHA IgM, AHA IgG, AGA IgM, and AGA IgG versus controls (p<0.0001 all comparisons). However, only APA IgM (p=0.03) and AHA IgM (p=0.03) levels were lower in the PHH versus non-PHH group in multivariate analysis. There were no differences in IgG levels by PHH status. Multiple inflammatory markers were positively correlated with IgM autoantibody production. PHH was associated with higher soluble tumor-necrosis-factor receptors I/II, (sTNFRI, sTNFRII), regulated on activation, normal T-Cell expressed and secreted (RANTES) and soluble interleukin-2-receptor-alpha (sIL-2Rα) levels. Higher IgM APA and AHA, but not AGA, in the absence of PHH may suggest a beneficial or reparative role for neuroendocrine tissue specific IgM autoantibody production against PHH development post-TBI.
Insomnia, Hypnotic Use, and Road Collisions: A Population-Based, 5-Year Cohort Study.

STUDY OBJECTIVES The study objectives were to examined accidental risks associated with insomnia or hypnotic medications, and how these risk factors interact with sex and age. METHODS A population-based sample of 3413 adults (Mage = 49.0 years old; 61.5% female), with or without insomnia, were surveyed annually for five consecutive years about their sleep patterns, sleep medication usage, and road collisions. RESULTS There was a significant risk of reporting road collisions associated with insomnia (HR =1.20; 95% CI = 1.00-1.45) and daytime fatigue (HR =1.21; 95% CI = 1.01-1.47). Insomnia or its daytime consequences were perceived to have played some contributory role in 40% of the reported collisions. Both chronic (HR = 1.50; 95% CI = 1.17-1.91) and regular use of sleep medications (HR = 1.58; 95% CI = 1.16 - 2.14) were associated with higher accidental risks, as well as being young female with insomnia and reporting excessive daytime sleepiness. CONCLUSIONS Both insomnia and use of sleep medications are associated with significant risks of road collisions, possibly because of or in association with some of their residual daytime consequences (i.e., fatigue, poor concentration). The findings also highlight a new group of at risk patients, i.e. young women reporting insomnia and excessive daytime sleepiness.
A novel way to synthesize pantothenate in bacteria involves β‐alanine synthase present in uracil degradation pathway

Pantothenate is an indispensable vitamin precursor of the synthesis of coenzyme A (CoA), a key metabolite required in over 100 metabolic reactions. β‐Alanine (β‐ala) is an indispensable component of pantothenate. Due to the metabolic relevance of this pathway, we assumed that orthologous genes for ß‐alanine synthesis would be present in the genomes of bacteria, archaea, and eukaryotes. However, comparative genomic studies revealed that orthologous gene replacement and loss of synteny occur at high frequency in panD genes. We have previously reported the atypical plasmid‐encoded location of the pantothenate pathway genes panC and panB (two copies) in R. etli CFN42. This study also revealed the unexpected absence of a panD gene encoding the aspartate decarboxylase enzyme (ADC), required for the synthesis of β‐ala. The aim of this study was to identify the source of β‐alanine in Rhizobium etli CFN42. In this study, we present a bioinformatic analysis and an experimental validation demonstrating that the source of β‐ala in this R. etli comes from β‐alanine synthase, the last enzyme of the uracil degradation pathway.
Optimal imaging windows of indocyanine green‐assisted near‐infrared dental imaging with rat model and its comparison to X‐ray imaging

In this study, we used rat animal model to compare the efficiency of indocyanine green (ICG)‐assisted dental near‐infrared fluorescence imaging with X‐ray imaging, and we optimized the imaging window for both unerupted and erupted molars. The results show that the morphology of the dental structures was observed clearly from ICG‐assisted dental images (especially through the endoscope). A better image contrast was easily acquired at the short imaging windows (<10 minutes) for unerupted and erupted molars. For unerupted molars, there is another optimized imaging window (48‐96 hours) with a prominent glow‐in‐the‐dark effect: only the molars remain bright. This study also revealed that the laser ablation of dental follicles can disrupt the molar development, and our method is able to efficiently detect laser‐treated molars and acquire the precise morphology. Thus, ICG‐assisted dental imaging has the potential to be a safer and more efficient imaging modality for the real‐time diagnosis of dental diseases.
The Vaginal Microbiome in U.S. Black Women: A Systematic Review.

Background: Advancements in next-generation sequencing have allowed for a more complete understanding of the vaginal microbiome and its role in health and disease. The role of race/ethnicity in the composition of the vaginal microbiome and what is deemed normal/healthy microbiome is conflicting. Thus, the purpose of this review is to synthesize research that investigated the vaginal microbiome in Black women in the United States by using advanced 16S analysis. Methods: Searches of Pubmed, Google Scholar, and relevant journals for publications between January 2008 and July 2018 were conducted. Eligibility criteria were that the study: (1) used a molecular technique for sequencing of the vaginal microbiome, (2) reported the microbiome by race/ethnicity that included Black women, and (3) was conducted in the United States. Results: Our review selected 18 manuscripts that met the inclusion criteria for full review. Three themes emerged: the vaginal microbiome in healthy women versus women with bacterial vaginosis (BV); vaginal microbiome considerations in HIV; and vaginal microbiome considerations in preterm labor/birth. Overall, our review found that a majority of Black women (including HIV-positive women) have a Lactobacillus dominant group. Specifically, Lactobacillus iners was the most frequently reported Lactobacillus species. Non-Lactobacillus dominant groups were also reported to be found in healthy asymptomatic Black women. The vaginal microbiome's influence on preterm labor and/or birth among Black women was inconclusive and warrants further investigation. Conclusions: The role that the microbiome plays in health and disease among Black women warrants further research to better elucidate the definition of a healthy versus pathogenic microbiome. The wide variability in methods for BV diagnostics and defining preterm labor/birth are significant limitations that should be considered when conducting comparative studies.
Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

Abstract The traditional chronic kidney disease (CKD) biomarkers (eGFR based on serum creatinine, sex and age and albuminuria) cannot predict a patient’s individual risk for developing progressive CKD. For this reason, it is necessary to identify novel CKD biomarkers that will be able to predict which patients are prone to develop progressive disease and discriminate between disease processes in different parts of the nephron (glomeruli or tubules). A good biomarker should change before or simultaneously with lesion development and its changes should correlate strongly with lesion development. Also, there should be a close relationship between severity of injury and amount of detectable biomarker and its levels should decrease with diminishing injury. Among the large number of molecules under investigation, we have reviewed the most promising ones: NGAL and KIM-1, MCP-1, MMP-9, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1 and suPAR. All these, have been studied as biomarkers for prediction of CKD progression in cohorts of patients with chronic kidney disease of different stages and various aetiologies (proteinuric and non-proteinuric, glomerulonephritides, diabetic, hypertensive and polycystic kidney disease). There is evidence that these molecules could be useful as biomarkers for progressive chronic kidney disease, however, the available data are not enough to draw final conclusions. Further studies with large cohorts and long follow-up are required to identify appropriate biomarkers, that will be able to accurately and reliably define the risk for progressive chronic kidney disease.
Extraction, Identification, Modification, and Antibacterial Activity of Histone from Immature Testis of Atlantic salmon

In the present study, histone from immature testis of Atlantic salmon was extracted and identified, and its antibacterial activity after enzymolysis was investigated. Histone extracted from Atlantic salmon (Salmo salar) testis using the acid extraction method was successfully identified by LC-MS/MS, and revealed significant inhibitory activity on both the Gram-negative and Gram-positive bacteria. With a low concentration of 10 mg/mL, the observed inhibitory zone diameter (IZD) could significantly reach up to 15.23 mm. After modification of enzymatic hydrolysis by pepsin, histone could be digested to three fragments, while the antibacterial activity increased up to 57.7%. All the results suggested the leftovers from commercial fishing could be utilized for the extraction of antimicrobial peptides.
Mangrove blue carbon stocks and dynamics are controlled by hydrogeomorphic settings and land‐use change

Globally, carbon‐rich mangrove forests are deforested and degraded due to land‐use and land‐cover change (LULCC). The impact of mangrove deforestation on carbon emissions has been reported on a global scale; however, uncertainty remains at subnational scales due to geographical variability and field data limitations. We present an assessment of blue carbon storage at five mangrove sites across West Papua Province, Indonesia, a region that supports 10% of the world's mangrove area. The sites are representative of contrasting hydrogeomorphic settings and also capture change over a 25‐years LULCC chronosequence. Field‐based assessments were conducted across 255 plots covering undisturbed and LULCC‐affected mangroves (0‐, 5‐, 10‐, 15‐ and 25‐year‐old post‐harvest or regenerating forests as well as 15‐year‐old aquaculture ponds). Undisturbed mangroves stored total ecosystem carbon stocks of 182–2,730 (mean ± SD: 1,087 ± 584) Mg C/ha, with the large variation driven by hydrogeomorphic settings. The highest carbon stocks were found in estuarine interior (EI) mangroves, followed by open coast interior, open coast fringe and EI forests. Forest harvesting did not significantly affect soil carbon stocks, despite an elevated dead wood density relative to undisturbed forests, but it did remove nearly all live biomass. Aquaculture conversion removed 60% of soil carbon stock and 85% of live biomass carbon stock, relative to reference sites. By contrast, mangroves left to regenerate for more than 25 years reached the same level of biomass carbon compared to undisturbed forests, with annual biomass accumulation rates of 3.6 ± 1.1 Mg C ha−1 year−1. This study shows that hydrogeomorphic setting controls natural dynamics of mangrove blue carbon stocks, while long‐term land‐use changes affect carbon loss and gain to a substantial degree. Therefore, current land‐based climate policies must incorporate landscape and land‐use characteristics, and their related carbon management consequences, for more effective emissions reduction targets and restoration outcomes.
Neurodevelopment of children exposed intra-uterus by Zika virus: A case series

The main goal of this manuscript was to investigate the neurodevelopment of children exposed by Zika virus in the intrauterine period who are asymptomatic at birth. Newborns with documented Zika virus exposure during the intrauterine period who were asymptomatic at birth were followed in the first two years of life for neurodevelopment using Bayley III test. Children were classified as having normal or delayed neurodevelopment for age based on most recent Bayley III evaluation results. Eighty-four infants were included in the study. The first Bayley III evaluation was performed at a mean chronological age of 9.7±3.1 month; 13 children (15%) had a delay in one of the three domains, distributed as follow: 10 (12%) in the language domain and 3 (3.5%) in the motor domain. The most recent Bayley III evaluation was performed at a mean age 15.3±3.1 months; 42 children (50%) had a delay in one of the three domains: 4 (5%) in cognition, 31 (37%) in language, and 20 (24%) in motor performance. There were no statistical differences in Gender, Gestational Age, Birth Weight and Head Circurference at birth between children with normal and delayed neurodevelopment for age. A very high proportion of children exposed ZIKV during pregnancy who were asymptomatic at birth demonstrated a delay in neurodevelopment, mainly in the language domain, the first two years of life.
The Magnitude of the Warfarin‐Amiodarone Drug‐Drug Interaction Varies With Renal Function: A Propensity‐Matched Cohort Study

Amiodarone inhibits warfarin metabolism and is associated with major bleeding during warfarin therapy. Managing this drug‐drug interaction (DDI) is challenging because of substantial interpatient variability in DDI magnitude. Because renal dysfunction induces changes in drug metabolism and protein binding that could alter cytochrome P450 inhibition mechanisms, we hypothesized that renal dysfunction alters the impact of the warfarin‐amiodarone DDI. We tested this question in a propensity‐matched cohort study of hospitalized patients with atrial fibrillation. Patients were queried from an electronic health record database. Renal function was estimated with creatinine clearance (CrCl). Warfarin response was measured with the warfarin sensitivity index (WSI), a dose‐normalized international normalized ratio (INR) measure, and was modeled with multilevel mixed‐effects linear regression. Time to supratherapeutic INR (> 4) was modeled using Cox regression. Propensity score matching resulted in 4,518 patients administered amiodarone and 4,518 controls. Amiodarone’s effect on warfarin response varied threefold across the renal function range, increasing WSI by 36% in patients with normal renal function (CrCl 115 mL/minute), but by only 11.8% in patients with severe renal dysfunction (CrCl 15 mL/minute). Similarly, amiodarone had a strong effect in patients with normal renal function (hazard ratio (HR) 1.80; 1.23, 2.64), but a negligible effect on supratherapeutic INR hazard in patients with severe renal dysfunction (HR 1.01; 0.75, 1.37). These results suggest that renal function is a novel factor that explains substantial variability in the warfarin‐amiodarone DDI. This information could inform warfarin dosage adjustment and monitoring and may have implications for the selection of oral anticoagulation agents in patients treated with amiodarone.
RFPR-IDP: reduce the false positive rates for intrinsically disordered protein and region prediction by incorporating both fully ordered proteins and disordered proteins

Abstract As an important type of proteins, intrinsically disordered proteins/regions (IDPs/IDRs) are related to many crucial biological functions. Accurate prediction of IDPs/IDRs is beneficial to the prediction of protein structures and functions. Most of the existing methods ignore the fully ordered proteins without IDRs during training and test processes. As a result, the corresponding predictors prefer to predict the fully ordered proteins as disordered proteins. Unfortunately, these methods were only evaluated on datasets consisting of disordered proteins without or with only a few fully ordered proteins, and therefore, this problem escapes the attention of the researchers. However, most of the newly sequenced proteins are fully ordered proteins in nature. These predictors fail to accurately predict the ordered and disordered proteins in real-world applications. In this regard, we propose a new method called RFPR-IDP trained with both fully ordered proteins and disordered proteins, which is constructed based on the combination of convolution neural network (CNN) and bidirectional long short-term memory (BiLSTM). The experimental results show that although the existing predictors perform well for predicting the disordered proteins, they tend to predict the fully ordered proteins as disordered proteins. In contrast, the RFPR-IDP predictor can correctly predict the fully ordered proteins and outperform the other 10 state-of-the-art methods when evaluated on a test dataset with both fully ordered proteins and disordered proteins. The web server and datasets of RFPR-IDP are freely available at http://bliulab.net/RFPR-IDP/server.
Pluripotent Stem Cell-Based Models: A Peephole into Virus Infections during Early Pregnancy

The rubella virus (RV) was the first virus shown to be teratogenic in humans. The wealth of data on the clinical symptoms associated with congenital rubella syndrome is in stark contrast to an incomplete understanding of the forces leading to the teratogenic alterations in humans. This applies not only to RV, but also to congenital viral infections in general and includes (1) the mode of vertical transmission, even at early gestation, (2) the possible involvement of inflammation as a consequence of an activated innate immune response, and (3) the underlying molecular and cellular alterations. With the progress made in the development of pluripotent stem cell-based models including organoids and embryoids, it is now possible to assess congenital virus infections on a mechanistic level. Moreover, antiviral treatment options can be validated, and newly emerging viruses with a potential impact on human embryonal development, such as that recently reflected by the Zika virus (ZIKV), can be characterized. Here, we discuss human cytomegalovirus (HCMV) and ZIKV in comparison to RV as viruses with well-known congenital pathologies and highlight their analysis on current models for the early phase of human development. This includes the implications of their genetic variability and, as such, virus strain-specific properties for their use as archetype models for congenital virus infections. In this review, we will discuss the use of induced pluripotent stem cells (iPSC) and derived organoid systems for the study of congenital virus infections with a focus on their prominent aetiologies, HCMV, ZIKV, and RV. Their assessment on these models will provide valuable information on how human development is impaired by virus infections; it will also add new insights into the normal progression of human development through the analysis of developmental pathways in the context of virus-induced alterations. These are exciting perspectives for both developmental biology and congenital virology.