Miracle-dz/UniFAR-FTUs huggingface dataset:
QTLbase: an integrative resource for quantitative trait loci across multiple human molecular phenotypes

Abstract Recent advances in genome sequencing and functional genomic profiling have promoted many large-scale quantitative trait locus (QTL) studies, which connect genotypes with tissue/cell type-specific cellular functions from transcriptional to post-translational level. However, no comprehensive resource can perform QTL lookup across multiple molecular phenotypes and investigate the potential cascade effect of functional variants. We developed a versatile resource, named QTLbase, for interpreting the possible molecular functions of genetic variants, as well as their tissue/cell-type specificity. Overall, QTLbase has five key functions: (i) curating and compiling genome-wide QTL summary statistics for 13 human molecular traits from 233 independent studies; (ii) mapping QTL-relevant tissue/cell types to 78 unified terms according to a standard anatomogram; (iii) normalizing variant and trait information uniformly, yielding >170 million significant QTLs; (iv) providing a rich web client that enables phenome- and tissue-wise visualization; and (v) integrating the most comprehensive genomic features and functional predictions to annotate the potential QTL mechanisms. QTLbase provides a one-stop shop for QTL retrieval and comparison across multiple tissues and multiple layers of molecular complexity, and will greatly help researchers interrogate the biological mechanism of causal variants and guide the direction of functional validation. QTLbase is freely available at http://mulinlab.org/qtlbase.
Yellow Fever Virus Reemergence and Spread in Southeast Brazil, 2016–2019

Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control. ABSTRACT The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espírito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics. IMPORTANCE Arbovirus infections in Brazil, including yellow fever, dengue, zika, and chikungunya, result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by the limited availability of genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from nonhuman primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in the field can augment traditional approaches to infectious disease surveillance and control.
Ostreolysin A and anthrolysin O use different mechanisms to control movement of cholesterol from the plasma membrane to the endoplasmic reticulum

Recent studies using two cholesterol-binding bacterial toxin proteins, perfringolysin O (PFO) and domain 4 of anthrolysin O (ALOD4), have shown that cholesterol in the plasma membranes (PMs) of animal cells resides in three distinct pools. The first pool comprises mobile cholesterol, accessible to both PFO and ALOD4, that is rapidly transported to the endoplasmic reticulum (ER) to signal cholesterol excess and maintain cholesterol homeostasis. The second is a sphingomyelin (SM)-sequestered pool inaccessible to PFO and ALOD4 but that becomes accessible by treatment with SM-degrading sphingomyelinase (SMase). The third is an essential pool also inaccessible to PFO and ALOD4 that cannot be liberated by SMase treatment. The accessible cholesterol pool can be trapped on PMs of live cells by nonlytic ALOD4, blocking its transport to the ER. However, studies of the two other pools have been hampered by a lack of available tools. Here, we used ostreolysin A (OlyA), which specifically binds SM/cholesterol complexes in membranes, to study the SM-sequestered cholesterol pool. Binding of nonlytic OlyA to SM/cholesterol complexes in PMs of live cells depleted the accessible PM cholesterol pool detectable by ALOD4. Consequently, transport of accessible cholesterol from PM to ER ceased, thereby activating SREBP transcription factors and increasing cholesterol synthesis. Thus, OlyA and ALOD4 both control movement of PM cholesterol, but through different lipid-binding mechanisms. We also found that PM-bound OlyA was rapidly internalized into cells, whereas PM-bound ALOD4 remained on the cell surface. Our findings establish OlyA and ALOD4 as complementary tools to investigate cellular cholesterol transport.
An exploration of neural dynamics of motor imagery for people with amyotrophic lateral sclerosis

Objective. Studies of the neuropathological effects of amyotrophic lateral sclerosis (ALS) on the underlying motor system have investigated abnormalities in the magnitude and timing of the event-related desynchronization (ERD) and synchronization (ERS) during motor execution (ME). However, the spatio-spectral-temporal dynamics of these sensorimotor oscillations during motor imagery (MI) have not been fully explored for these patients. This study explores the neural dynamics of sensorimotor oscillations for ALS patients during MI by quantifying ERD/ERS features in frequency, time, and space. Approach. Electroencephalogram (EEG) data were recorded from six patients with ALS and 11 age-matched healthy controls (HC) while performing a MI task. ERD/ERS features were extracted using wavelet-based time-frequency analysis and compared between the two groups to quantify the abnormal neural dynamics of ALS in terms of both time and frequency. Topographic correlation analysis was conducted to compare the localization of MI activity between groups and to identify subject-specific frequencies in the µ and β frequency bands. Main results. Overall, reduced and delayed ERD was observed for ALS patients, particularly during right-hand MI. ERD features were also correlated with ALS clinical scores, specifically disease duration, bulbar, and cognitive functions. Significance. The analyses in this study quantify abnormalities in the magnitude and timing of sensorimotor oscillations for ALS patients during MI tasks. Our findings reveal notable differences between MI and existing results on ME in ALS. The observed alterations are speculated to reflect disruptions in the underlying cortical networks involved in MI functions. Quantifying the neural dynamics of MI plays an important role in the study of EEG-based cortical markers for ALS.
Female adult zebrafish (Danio rerio) show higher levels of anxiety‐like behavior than males, but do not differ in learning and memory capacity

Zebrafish (Danio rerio) are widely used as a translational model for human neuropsychiatric conditions. Many studies have not considered sex differences in their analyses. Here, we studied sex differences of adult zebrafish in two behavioral domains: Anxiety and Memory. To assess whether sex influences anxiety‐like responses, we used two different behavioral protocols, the novel tank diving task and the light–dark test. To assess sex differences in learning and memory tasks, we explored two memory domains, short‐term spatial memory (free movement pattern Y‐maze task) and short‐term fear memory (Pavlovian fear‐conditioning task). Although we did not find any significant difference in learning and memory tasks, female zebrafish showed robust increases in anxiety‐like behavioral endpoints in both anxiety tests. Overall, our data suggest that zebrafish is a sensitive model to work with sex differences when modeling anxiety‐related disorders and this should be an important factor to consider in different experimental designs.
Morphological and Molecular Characterization of Three Endolichenic Isolates of Xylaria (Xylariaceae), from Cladonia curta Ahti & Marcelli (Cladoniaceae)

Endophyte biology is a branch of science that contributes to the understanding of the diversity and ecology of microorganisms that live inside plants, fungi, and lichen. Considering that the diversity of endolichenic fungi is little explored, and its phylogenetic relationship with other lifestyles (endophytism and saprotrophism) is still to be explored in detail, this paper presents data on axenic cultures and phylogenetic relationships of three endolichenic fungi, isolated in laboratory. Cladonia curta Ahti & Marcelli, a species of lichen described in Brazil, is distributed at three sites in the Southeast of the country, in mesophilous forests and the Cerrado. Initial hyphal growth of Xylaria spp. on C. curta podetia started four days after inoculation and continued for the next 13 days until the hyphae completely covered the podetia. Stromata formation and differentiation was observed, occurring approximately after one year of isolation and consecutive subculture of lineages. Phylogenetic analyses indicate lineages of endolichenic fungi in the genus Xylaria, even as the morphological characteristics of the colonies and anamorphous stromata confirm this classification. Our preliminary results provide evidence that these endolichenic fungi are closely related to endophytic fungi, suggesting that the associations are not purely incidental. Further studies, especially phylogenetic analyses using robust multi-locus datasets, are needed to accept or reject the hypothesis that endolichenic fungi isolated from Xylaria spp. and X. berteri are conspecific.
Targeting Angiogenesis in Pancreatic Neuroendocrine Tumors: Resistance Mechanisms

Despite being infrequent tumors, the incidence and prevalence of pancreatic neuroendocrine tumors (P-NETs) has been rising over the past few decades. In recent years, rigorous phase III clinical trials have been conducted, allowing the approval of several drugs that have become the standard of care in these patients. Although various treatments are used in clinical practice, including somatostatin analogues (SSAs), biological therapies like sunitinib or everolimus, peptide receptor radionuclide therapy (PRRT) or even chemotherapy, a consensus regarding the optimal sequence of treatment has not yet been reached. Notwithstanding, sunitinib is largely used in these patients after the promising results shown in SUN111 phase III clinical trial. However, both prompt progression as well as tumor recurrence after initial response have been reported, suggesting the existence of primary and acquired resistances to this antiangiogenic drug. In this review, we aim to summarize the most relevant mechanisms of angiogenesis resistance that are key contributors of tumor progression and dissemination. Furthermore, several targeted molecules acting selectively against these pathways have shown promising results in preclinical models, and preliminary results from ongoing clinical trials are awaited.
Association of Corneal Hysteresis With Lamina Cribrosa Curvature in Primary Open Angle Glaucoma.

Purpose To investigate whether corneal biomechanical properties are associated with the lamina cribrosa (LC) curvature in eyes with primary open angle glaucoma (POAG). Methods Corneal biomechanical properties and LC curvature were assessed in 65 treatment-naïve POAG patients. Corneal biomechanical properties, including corneal hysteresis (CH), corneal resistance factor (CRF), and corneal-compensated intraocular pressure (IOPcc), were measured using an ocular response analyzer (ORA; Reichert Ophthalmic Instruments). LC curvature was assessed by measuring the LC curvature index (LCCI) on B-scan images obtained using spectral-domain optical coherence tomography (OCT). The LCCI was determined by measuring LC curve depth on the anterior LC surface and the width of the reference line. Results The LCCI was correlated with CH (P = 0.001), CRF (P = 0.012) and IOPcc (P = 0.001) in the univariate analysis. To adjust multicollinearity, principal component analysis was performed, and multivariate regression analyses were conducted using one variable from each component. The larger LCCI was associated with larger IOPcc (P < 0.001), smaller CRF (P = 0.001) and smaller CH (P < 0.001). Conclusions Lower CH was associated with a more posteriorly curved LC in treatment naïve POAG patients. This finding may provide a basic explanation for the reported association between CH and an increased risk for glaucoma development and progression, and support a potential value of CH for risk assessment for glaucoma.
Retroelement-Linked H3K4me1 Histone Tags Uncover Regulatory Evolution Trends of Gene Enhancers and Feature Quickly Evolving Molecular Processes in Human Physiology

Background: Retroelements (REs) are mobile genetic elements comprising ~40% of human DNA. They can reshape expression patterns of nearby genes by providing various regulatory sequences. The proportion of regulatory sequences held by REs can serve a measure of regulatory evolution rate of the respective genes and molecular pathways. Methods: We calculated RE-linked enrichment scores for individual genes and molecular pathways based on ENCODE project epigenome data for enhancer-specific histone modification H3K4me1 in five human cell lines. We identified consensus groups of molecular processes that are enriched and deficient in RE-linked H3K4me1 regulation. Results: We calculated H3K4me1 RE-linked enrichment scores for 24,070 human genes and 3095 molecular pathways. We ranked genes and pathways and identified those statistically significantly enriched and deficient in H3K4me1 RE-linked regulation. Conclusion: Non-coding RNA genes were statistically significantly enriched by RE-linked H3K4me1 regulatory modules, thus suggesting their high regulatory evolution rate. The processes of gene silencing by small RNAs, DNA metabolism/chromatin structure, sensory perception/neurotransmission and lipids metabolism showed signs of the fastest regulatory evolution, while the slowest processes were connected with immunity, protein ubiquitination/degradation, cell adhesion, migration and interaction, metals metabolism/ion transport, cell death, intracellular signaling pathways.
BiomeNet: a database for construction and analysis of functional interaction networks for any species with a sequenced genome

Abstract Motivation Owing to advanced DNA sequencing and genome assembly technology, the number of species with sequenced genomes is rapidly increasing. The aim of the recently launched Earth BioGenome Project is to sequence genomes of all eukaryotic species on Earth over the next 10 years, making it feasible to obtain genomic blueprints of the majority of animal and plant species by this time. Genetic models of the sequenced species will later be subject to functional annotation, and a comprehensive molecular network should facilitate functional analysis of individual genes and pathways. However, network databases are lagging behind genome sequencing projects as even the largest network database provides gene networks for less than 10% of sequenced eukaryotic genomes, and the knowledge gap between genomes and interactomes continues to widen. Results We present BiomeNet, a database of 95 scored networks comprising over 8 million co-functional links, which can build and analyze gene networks for any species with the sequenced genome. BiomeNet transfers functional interactions between orthologous proteins from source networks to the target species within minutes and automatically constructs gene networks with the quality comparable to that of existing networks. BiomeNet enables assembly of the first-in-species gene networks not available through other databases, which are highly predictive of diverse biological processes and can also provide network analysis by extracting subnetworks for individual biological processes and network-based gene prioritizations. These data indicate that BiomeNet could enhance the benefits of decoding the genomes of various species, thus improving our understanding of the Earth’ biodiversity. Availability and implementation The BiomeNet is freely available at http://kobic.re. kr/biomenet/. Supplementary information Supplementary data are available at Bioinformatics online.
Media switching at different time periods affects the reprogramming efficiency of buffalo fetal fibroblasts

Abstract Many contrasting reports are available on generation of bovine induced pluripotent stem cells (iPSCs) employing different timelines and culture conditions which signifies reprogramming process varies between species and cell types. The present study determines an optimum time period required to re-initiate reprogramming events in buffalo fibroblasts after introduction of exogenous genes (OCT4, SOX2, KLF4 and c-MYC) by lentiviral vector. The reprogramming efficiency is cumulative result of many factors including culture conditions and addition of growth factors in culture media. In our study, we observed when stem cell culture conditions were provided Day 5 post-transduction, it results in maximum reprogramming efficiency in comparison when same conditions were provided too early or on later days. The putative iPSCs were expanded on feeder layer for 15 passages and found positive for alkaline phosphatase and pluripotency markers (OCT4, SOX2, KLF4, c-MYC, UTF, TELOMERASE, FOXD3, REX1, STAT3, NUCLEOSTAMIN and TRA1-81). Also, they produced embryoid bodies showing expression for ectodermal (NF68, MOBP), mesodermal (ASA, BMP4) and endodermal (GATA4, AFP) markers to confirm their pluripotent nature. Our results suggest that reprogramming is accompanied by time dependent events and providing stem cell culture conditions at definite time during reprogramming can help in generation of iPSCs with greater efficiency.
Comparing the potential causal influence of two indicators of early alcohol use on later alcohol use disorder symptoms.

Age of first drink (AFD) has repeatedly been found to be associated with alcohol use disorder (AUD); however, some studies suggest this is a noncausal effect that may be due to childhood risk factors or familial influences. In contrast to indicators of any early alcohol use, such as AFD, indicators of a pattern of repeated drinking may be more likely to be causally associated with later problematic alcohol use. The current study examined AFD and age of onset of regular drinking (ARD; defined as drinking at least once a month for 6 or more months) as quasicausal predictors of lifetime AUD symptoms. Participants were 3,005 adult Australian twins who reported having been regular drinkers in their lifetime. Semistructured interviews were conducted to assess AFD, ARD, AUD, externalizing symptomatology, and other substance use. Personality traits were assessed via questionnaire. Unadjusted and adjusted multilevel discordant twin models were conducted using data from 1,041 complete twin pairs; adjusted models included socioeconomic status, personality, conduct disorder, and early initiation of regular smoking and marijuana use as covariates. Results from fully adjusted models controlling for familial confounds provided evidence for a causal influence of ARD on AUD symptoms, whereby twins with an earlier age of regular drinking than their cotwin had more lifetime AUD symptoms. However, AFD did not significantly predict AUD symptoms after adjusting for confounds. These results suggest that early regular drinking may serve as a causal risk factor for future problems, while early initiation of any alcohol use may indicate genetic liability. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Growth-promoting effects of the hydrogen-sulfide compounds produced by Desulfovibrio desulfuricans subsp. desulfuricans co-cultured with Escherichia coli (DH5α) on the growth of Entamoeba and Endolimax species isolates from swine.

Certain Desulfovibrio sp. (anaerobic sulfate-reducing bacteria) are indigenous to swine cecum and colon, which are also common habitats for parasitic amoebae such as Entamoeba polecki and Entamoeba suis. In this study, we evaluated the growth-promoting effects of D. desulfuricans co-cultured with Escherichia coli (DH5α) and its products [e.g., hydrogen sulfide (H2S) and certain iron-sulfide (FeS) compounds] using Robinson's medium, on the 4 amoeba isolates from swine-Entamoeba polecki subtype (ST)-1, E. polecki ST-3, Entamoeba suis, and Endolimax sp. , and, consequently, a continuous culture system for these amoebae was established. However, this novel culture system was required to regulate the excess H2S dissolved in the medium by increasing air space as amoeba isolates thrive only in large air spaces (30-40%). The effects of air space and H2S and FeS compounds on the growth of E. polecki ST-1 (TDP-5) were determined. E. polecki ST-1 (TDP-5) thrived well in culture bottles with an air space of 30-40% (aerobic) (H2S: ~250-400 μmoles/L), but did not grow at all in an air space < 5% (microaerobic) ( H2S:~800 μmoles/L) and in anaerobic vessels (H2S: 20-30 μmoles/L). In both H2S-depleted and FeS compound-depleted conditions, the amoebae sp. could not thrive either. It was hypothesized that an appropriate concentration of H2S and FeS compounds might function as important physiologically active components of electron carriers such as FeS and ferredoxin.