Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Scale Profiling Reveals Noncoding Loci Carry Higher Proportions of Concordant Data

Abstract Many evolutionary relationships remain controversial despite whole-genome sequencing data. These controversies arise, in part, due to challenges associated with accurately modeling the complex phylogenetic signal coming from genomic regions experiencing distinct evolutionary forces. Here, we examine how different regions of the genome support or contradict well-established relationships among three mammal groups using millions of orthologous parsimony-informative biallelic sites (PIBS) distributed across primate, rodent, and Pecora genomes. We compared PIBS concordance percentages among locus types (e.g. coding sequences (CDS), introns, intergenic regions), and contrasted PIBS utility over evolutionary timescales. Sites derived from noncoding sequences provided more data and proportionally more concordant sites compared with those from CDS in all clades. CDS PIBS were also predominant drivers of tree incongruence in two cases of topological conflict. PIBS derived from most locus types provided surprisingly consistent support for splitting events spread across the timescales we examined, although we find evidence that CDS and intronic PIBS may, respectively and to a limited degree, inform disproportionately about older and younger splits. In this era of accessible wholegenome sequence data, these results:1) suggest benefits to more intentionally focusing on noncoding loci as robust data for tree inference and 2) reinforce the importance of accurate modeling, especially when using CDS data.
Computational resources for identifying and describing proteins driving liquid–liquid phase separation

Abstract One of the most intriguing fields emerging in current molecular biology is the study of membraneless organelles formed via liquid–liquid phase separation (LLPS). These organelles perform crucial functions in cell regulation and signalling, and recent years have also brought about the understanding of the molecular mechanism of their formation. The LLPS field is continuously developing and optimizing dedicated in vitro and in vivo methods to identify and characterize these non-stoichiometric molecular condensates and the proteins able to drive or contribute to LLPS. Building on these observations, several computational tools and resources have emerged in parallel to serve as platforms for the collection, annotation and prediction of membraneless organelle-linked proteins. In this survey, we showcase recent advancements in LLPS bioinformatics, focusing on (i) available databases and ontologies that are necessary to describe the studied phenomena and the experimental results in an unambiguous way and (ii) prediction methods to assess the potential LLPS involvement of proteins. Through hands-on application of these resources on example proteins and representative datasets, we give a practical guide to show how they can be used in conjunction to provide in silico information on LLPS.
miRNAs in Microglia: Important Players in Multiple Sclerosis Pathology

Microglia are the resident immune cells of the central nervous system and important regulators of brain homeostasis. Central to this role is a dynamic phenotypic plasticity that enables microglia to respond to environmental and pathological stimuli. Importantly, different microglial phenotypes can be both beneficial and detrimental to central nervous system health. Chronically activated inflammatory microglia are a hallmark of neurodegeneration, including the autoimmune disease multiple sclerosis (MS). By contrast, microglial phagocytosis of myelin debris is essential for resolving inflammation and promoting remyelination. As such, microglia are being explored as a potential therapeutic target for MS. MicroRNAs (miRNAs) are short non-coding ribonucleic acids that regulate gene expression and act as master regulators of cellular phenotype and function. Dysregulation of certain miRNAs can aberrantly activate and promote specific polarisation states in microglia to modulate their activity in inflammation and neurodegeneration. In addition, miRNA dysregulation is implicated in MS pathogenesis, with circulating biomarkers and lesion specific miRNAs identified as regulators of inflammation and myelination. However, the role of miRNAs in microglia that specifically contribute to MS progression are still largely unknown. miRNAs are being explored as therapeutic agents, providing an opportunity to modulate microglial function in neurodegenerative diseases such as MS. This review will focus firstly on elucidating the complex role of microglia in MS pathogenesis. Secondly, we explore the essential roles of miRNAs in microglial function. Finally, we focus on miRNAs that are implicated in microglial processes that contribute directly to MS pathology, prioritising targets that could inform novel therapeutic approaches to MS.
Predicting Lymph Node Metastasis Using Computed Tomography Radiomics Analysis in Patients With Resectable Esophageal Squamous Cell Carcinoma.

OBJECTIVES We investigated the value of radiomics data, extracted from pretreatment computed tomography images of the primary tumor (PT) and lymph node (LN) for predicting LN metastasis in esophageal squamous cell carcinoma (ESCC) patients. MATERIALS AND METHODS A total 338 ESCC patients were retrospectively assessed. Primary tumor, the largest short-axis diameter LN (LSLN), and PT and LSLN interaction term (IT) radiomic features were calculated. Subsequently, the radiomic signature was combined with clinical risk factors in multivariable logistic regression analysis to build various clinical-radiomic models. Model performance was evaluated with respect to the fit, overall performance, differentiation, and calibration. RESULTS A clinical-radiomic model, which combined clinical and PT-LSLN-IT radiomic signature, showed favorable discrimination and calibration. The area under curve value was 0.865 and 0.841 in training and test set. CONCLUSIONS A venous computed tomography radiomic model based on the PT, LSLN, and IT radiomic features represents a novel noninvasive tool for prediction LN metastasis in ESCC.
Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria

ABSTRACT Introduction: In erythropoietic protoporphyria (EPP), an inherited disorder of heme biosynthesis, accumulation of protoporphyrin IX results in acute phototoxicity. EPP patients experience severe burning pain after light exposure, which results in a markedly reduced quality of life. Afamelanotide is the first effective approved medical treatment for EPP, acting on melanocortin-1 receptors. This article aims to review afamelanotide. Areas covered: This review summarizes the chemical properties, pharmacokinetics, safety, preclinical and clinical data on afamelanotide in EPP, and post-marketing surveillance. PubMed search, manufacturers’ websites, and relevant articles used for approval by authorities were used for the literature search. Expert opinion: Afamelanotide is an α-melanocyte-stimulating hormone analog. It can activate eumelanogenesis without exposure to UV radiation. Clinical studies in EPP showed that afamelanotide treatment significantly increased exposure to sunlight and QoL. In our clinical experience afamelanotide treatment is much more effective in clinical practice than demonstrated in clinical trials and should be made available for all EPP patients meeting inclusion criteria. The 60-day interval period was not based on effectiveness studies, and therefore for some of the patients the maximum of four implants per year with the 60-day interval is insufficient. Afamelanotide is well tolerated; common adverse events were headache, fatigue, and nausea.
Demographic and Mental Health Predictors of Arrests Up to 10 Years Post-Traumatic Brain Injury: A Veterans Affairs TBI Model Systems Study

Supplemental Digital Content is Available in the Text. Objective: Examine rates and predictors of arrests in Veterans and Service Members (V/SM) who received inpatient rehabilitation for traumatic brain injury (TBI). Setting: Veterans Administration (VA) Polytrauma Rehabilitation Centers. Participants: A total of 948 V/SM drawn from the VA TBI Model Systems cohort with arrest data up to 10 years post-TBI. Design: Longitudinal cohort study; secondary analysis of pre-TBI characteristics predicting post-TBI arrests. Main Measures: Disclosure of arrests pre-TBI and up to10 years post-TBI. Results: Thirty-six percent of the sample had been arrested prior to their TBI; 7% were arrested post-TBI. When considering all variables simultaneously in a multivariate model, pre-TBI mental health treatment (adjusted odds ratio [aOR] = 4.30; 95% confidence interval [CI]: 2.03-9.14), pre-TBI heavy alcohol use (aOR = 3.04; CI: 1.08-8.55), and number of follow-up interviews (aOR = 2.05; CI: 1.39-4.50) were significant predictors of post-TBI arrest. Conclusion: Arrest rates of V/SM prior to TBI were consistent with rates of arrest for people of similar ages in the United States. Post-TBI rates were lower for V/SM than published rates of post-TBI arrests in civilians with TBI. As part of rehabilitation planning for V/SM with TBI, providers should assess for preinjury mental health services and alcohol misuse to (1) identify those who may be at risk for postinjury arrests and (2) provide relevant resources and/or supports.
Usefulness of CHADS2, R2CHADS2, and CHA2DS2‐VASc scores for predicting incident atrial fibrillation in heart failure with preserved ejection fraction patients

Coexisting of atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) could increase the risk of mortality. In this study, we aimed to assess the values of the CHADS2, R2CHADS2, and CHA2DS2‐VASc scores for AF prediction in HFpEF patients.
Peripheral immune tolerance by prolactin-induced protein originated from human invariant natural killer T cells

ABSTRACT invariant natural killer T (iNKT) cells have been reported to regulate a diverse set of immunological responses. iNKT cell dysfunction in cytokine secretion is linked to the development of autoimmunity, an immune response against its own tissue. Interestingly, CD4+ iNKT cells preferentially secrete regulatory cytokines. Here we investigated what kind of secreting factors of it are involved in dendritic cell (DC) maturation to regulate immune responses. We found one of them, prolactin induced protein (PIP), from the supernatants of cultured CD4+ iNKT cells. It was validated using RT-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis. Subsequent analysis upon PIP treatment was performed using fluorescence-activated cell sorting (FACS) analysis. We identified PIP as one of strong candidates for inducing DC maturation, to similar level to lipopolysaccharide, an already known candidate molecule. Recombinant PIP recapitulated natural function, and induction of DC differentiation by both recombinant and purified PIP was blocked by anti-Toll-like receptor (TLR)2 antibody (Ab), but not by anti-TLR4/5 or anti-receptor Ab for advanced glycation end product Ab. Interestingly, PIP induced the differentiation of naïve T cells into CD4+ CD25+ Foxp3+ regulatory T cells and reduced the number of helper T (Th)1 and Th17 cells produced by Pam3CysSerLys4. Take in together, these results suggest that PIP is an important factor that mediates immunoregulation by iNKT cells through TLR2-mediated signaling. Graphical abstract
Antibiotic Resistance, Biofilm Formation, and Presence of Genes Encoding Virulence Factors in Strains Isolated from the Pharmaceutical Production Environment

The spread of bacterial resistance to antibiotics affects various areas of life. The aim of this study was to assess the occurrence of Pseudomonas aeruginosa, and other bacteria mainly from orders Enterobacterales and Staphylococcus in the pharmaceutical production sites, and to characterize isolated strains in the aspects of antibiotic resistance, biofilm formation, and presence of genes encoding virulence factors. Genes encoding selected virulence factors were detected using PCR techniques. Antimicrobial susceptibility testing was applied in accordance with the EUCAST recommendations. A total of 46 P. aeruginosa strains were isolated and 85% strains showed a strong biofilm-forming ability. The qualitative identification of genes taking part in Quorum Sensing system demonstrated that over 89% of strains contained lasR and rhlI genes. An antimicrobial susceptibility testing revealed nine strains resistant to at least one antibiotic, and two isolates were the metallo-β-lactamase producers. Moreover, the majority of P. aeruginosa strains contained genes encoding various virulence factors. Presence of even low level of pathogenic microorganisms or higher level of opportunistic pathogens and their toxic metabolites might result in the production inefficiency. Therefore, the prevention of microbial contamination, effectiveness of sanitary and hygienic applied protocols, and constant microbiological monitoring of the environment are of great importance.
Inflammatory versus Anti-Inflammatory Profiles in Major Depressive Disorders—The Role of IL-17, IL-21, IL-23, IL-35 and Foxp3

Background: The authors of this research study intended to verify whether there are any changes in gene expression in depressed patients without coexisting inflammatory diseases for selected immune-inflammatory factors that are particularly important in autoimmune disease pathogenesis (IL-17, IL-21, IL-23, IL-35, Foxp3). Methods: The study was carried out on a group of 190 patients with depression and 100 healthy volunteers. The severity of depressive symptoms was assessed using the Hamilton Depression Scale. RT-PCR was used to evaluate mRNA expression and ELISA was used to measure protein expression of these genes. Results: The level of gene expression for IL-17, IL-21, IL-23, and IL-35 was substantially higher in the group of patients with depression compared to the control group. The mean mRNA expression of Foxp3 was considerably reduced in patients suffering from depressive disorders. There was a statistically significant correlation between the number of hospitalizations and the expression of specific inflammatory factors. Conclusions: Expression of specific inflammatory genes may be a factor in the etiopathogenesis of depressive disorders. The duration of the disease seems to be more important for the expression of the genes in question than the severity of depression. These cytokines may affect the metabolism of neurotransmitters and neuroendocrine functions in the brain as well as be a marker and a new potential therapeutic target for recurrent depressive disorders.
I remember being nice: self-enhancement memory bias in middle childhood

ABSTRACT Adults tend to remember themselves in a positive way. For example, they are more likely to remember their past good deeds rather than their past bad deeds. We investigated whether children (N = 40) are also biased in how they remember information related to themselves. Using the self-reference memory paradigm, we found that 8- to 10-year-olds’ source memory for mean action phrases (e.g., “Lie to someone”) was worse when the phrases were encoded with reference to themselves compared to when they were encoded with reference to others. Source memory for self-referenced mean phrases was also worse than source memory for self-referenced nice action phrases (e.g., “Be kind to someone”) and self-referenced neutral action phrases (e.g., “Draw a circle”). These results provide some of the first experimental evidence for self-enhancement in children's memory.
MTHFR Polymorphisms in Girls with Anorexia Nervosa: Implications on Body Weight

ABSTRACT The development of atypical vs typical anorexia nervosa (AN) might be explained by the genetic background. We assessed the link between the subtypes of AN and the genetic polymorphisms of the thrombotic panel and the methyltetrahydrofolate reductase (MTHFR) gene. This cross-sectional pilot study recruited 48 girls with AN and 10 age-matched control girls with normal menstruation. We recorded anthropometric parameters and obtained blood samples for genotyping and hormonal assessment. Classification of AN was performed according to the DSM-V criteria. Girls with AN had 2.66 times higher odds of carrying at least one genetic polymorphism from the MTHFR panel (C677T and A1298C) compared with girls without AN (OR = 2.660, p-value = 0.041; CI 95% 1.057–6.720). The presence of atypical vs typical AN was associated independently with the presence of any of the assessed MTHFR polymorphisms (C677T, OR = 4.929, 95% CI 1.076–22.579, p-value = 0.040; A1298C, OR = 0.097, 95% CI 0.011–0.866, p-value = 0.037) in age and estrogen adjusted models. The atypical presentation of AN is mainly linked with higher prevalence of the MTHFR C677T and lower prevalence of the A1298C polymorphism.
Genome sequencing and analysis of plant growth-promoting attributes from Leclercia adecarboxylata

Abstract Plant growth-promoting bacteria are ecological alternatives for fertilization, mainly for gramineous. Since plant x bacteria interaction is genotype and strain dependent, searching for new strains may contribute to the development of new biofertilizers. We aim to characterize plant growth-promoting capacity of Leclercia adecarboxylata strain Palotina, formerly isolated by our group in corn. A single isolated colony was taken and its genome was sequenced using Illumina technology. The whole genome was compared to other Leclercia adecarboxylata strains, and their biological and growth-promoting traits, such as P solubilization and auxin production, were tested. Following that, a 4.8 Mb genome of L. adecarboxylata strain Palotina was assembled and the functional annotation was carried out. This paper is the first to report the genes associated with plant growth promotion demonstrating in vitro indole acid production by this strain. These results project the endophyte as a potential biofertilizer for further commercial exploitation.
Homotypic and Heterotypic Protection and Risk of Reinfection Following Natural Norovirus Infection in a Highly Endemic Setting

Abstract Background Norovirus is a leading cause of acute gastroenteritis worldwide, yet there is limited information on homotypic or heterotypic protection following natural infection to guide vaccine development. Methods A total of 6020 stools collected from 299 Peruvian children between 2010 and 2014 were tested by norovirus real-time reverse-transcription polymerase chain reaction followed by sequence-based genotyping. Cox proportional hazards models were used to derive adjusted hazard ratios (HRs) of infection among children with vs without prior exposure. Results Norovirus was detected in 1288 (21.3%) samples. GII.4 (26%), GII.6 (19%), and GI.3 (9%) viruses accounted for 54% of infections. Homotypic protection for GI.3 (HR, 0.35; P = .015), GI.7 (HR, 0.19; P = .022), GII.4 (HR, 0.39; P < .001), and GII.6 (HR, 0.52; P = .006) infections was observed. Hazard analysis showed that children with prior GII.4 infection exhibited heterotypic protection with a 48% reduction of subsequent GI.3 infection (HR, 0.52; P = .005). Prior exposure to GI.3, GII.2, and GII.17 infections enhanced susceptibility to subsequent infections with several other norovirus genotypes. Conclusions Children up to 2 years of age infected with GII.4 noroviruses demonstrated both homotypic and heterotypic protection to reinfection with other genotypes. These data support the need for ongoing vaccine development efforts with GII.4 as the main component and caution the inclusion of genotypes that may enhance susceptibility to infections.
Phage phiKZ—The First of Giants

The paper covers the history of the discovery and description of phiKZ, the first known giant bacteriophage active on Pseudomonas aeruginosa. It also describes its unique features, especially the characteristic manner of DNA packing in the head around a cylinder-shaped structure (“inner body”), which probably governs an ordered and tight packaging of the phage genome. Important properties of phiKZ-like phages include a wide range of lytic activity and the blue opalescence of their negative colonies, and provide a background for the search and discovery of new P. aeruginosa giant phages. The importance of the phiKZ species and of other giant phage species in practical phage therapy is noted given their broad use in commercial phage preparations.
In Vitro Anticoccidial Activities of the Extract and Fractions of Garcinia kola (Heckel h.) against Eimeria tenella Oocyst.

BACKGROUND Commercial poultry farming is expanding every day and contributing to the provision of affordable and high quality protein. However, this sector is confronted with many diseases of which coccidiosis is among the most important. There are many registered patents affirming the health benefits of Garcinia kola in poultry. OBJECTIVE Evaluation of In vitro anticoccidial activities of the extracts and fractions of Garcinia kola against Eimeria tenella oocyst was carried out. METHOD Fresh seeds of G. kola were collected, dried under shade at room temperature and pulverized using a mortar and a pestle. The powder was exhaustively extracted with a soxhlet apparatus using 70% methanol and the crude methanol extract (CME) was concentrated to dryness using a rotary evaporator. The CME was further partitioned using butanol, ethylacetate and n-hexane. The CME, butanol fraction (BTF), ethylacetate fraction (EAF) and hexane fraction (HXF) were concentrated in vacuo and tested for the presence of phytochemical constituents using standard procedures. Similarly the CME, butanol, ethyl acetate and hexane fractions were evaluated in vitro for oocyst sporulation inhibition. RESULTS Phytochemical analysis revealed the presence of cardiac glycosides, saponins, carbohydrates, steroids/triterpenes, tannins, flavonoids and alkaloids in the CME and BTF. The EAF contains all the metabolites mentioned except saponins. Similarly, HXF contains only cardiac glycosides, tannins and steroids/triterpenes. The CME and BTF caused a concentration dependent increase in the inhibition of sporulation of unsporulated oocysts of E. tenella. In the acute toxicity studies, the CME did not produce any toxic effect or mortality at doses between 10 and 5000 mg/kg. The CME was then considered safe and the LD50 was assumed to be >5000 mg/kg. CONCLUSION The data obtained in this study suggest that the crude methanol extract (CME) of G. kola could be appreciable beneficial effect as an anticoccidial agent against Eimeria tenella oocyst.
Trends and Applications in Plant Volatile Sampling and Analysis.

Volatile organic compounds (VOCs) released by plants serve as info- and defense chemicals in mutualistic and antagonistic interactions and mitigate effects of abiotic stress. Passive and dynamic sampling techniques combined with gas chromatography-mass spectrometry (GC-MS) analysis have become routine tools to measure emissions of VOCs and determine their various functions. More recently, knowledge of the roles of plant VOCs in the aboveground environment has led to the exploration of similar functions in the soil and rhizosphere. Moreover, VOC patterns have been recognized as sensitive and time-dependent markers of biotic and abiotic stress. This focused review addresses these developments by presenting recent progress in VOC sampling and analysis. We show advances in the use of small, inexpensive sampling devices and describe methods to monitor plant VOC emissions in the belowground environment. We further address latest trends in real-time measurements of volatilomes in plant phenotyping and most recent developments of small portable devices and VOC sensors for non-invasive VOC fingerprinting of plant disease. These technologies allow for innovative approaches to study plant VOC biology and application in agriculture.