bluuebunny/crossref_metadata_2025_split huggingface dataset:
Focusing on human haplotype diversity in numerous individual genomes demonstrates an evolutional feature of each locus
Authors: Shimada Makoto K. , Nishida Tsunetoshi 
Published: March 2020

AbstractThe application of current genome-wide sequencing techniques on human populations helps elucidate the considerable gene flow among genusHomo, which includes modern and archaic humans. Gene flow among current human populations has been studied using frequencies of single nucleotide polymorphisms. Unlike single nucleotide polymorphism frequency data, haplotype data are suitable for identifying and tracing rare evolutionary events. Haplotype data can also conveniently detect genomic location and estimate molecular function that may be a target of selection. We analyzed eight loci of the human genome using the same procedure for each locus to infer human haplotype diversity and reevaluate past explanations of the evolutionary mechanisms that affected these loci. These loci have been recognized by separate studies because of their unusual gene genealogy and geographic distributions that are inconsistent with the recent out-of-Africa model. For each locus, we constructed genealogies for haplotypes using sequence data of the 1000 Genomes Project. Then, we performed S* analysis to estimate distinct gene flow events other than out-of-Africa events. Furthermore, we also estimated unevenness of selective pressure between haplotypes by Extended Haplotype Homozygosity analysis. Based on the patterns of results obtained by this combination of analyses, we classified the examined loci without using a specific population model. This simple method helped clarify evolutionary events for each locus, including rare evolutionary events such as introgression, incomplete lineage sorting, selection, and haplotype recombination that may be hard to discriminate from each other.
Genetic exploration of a nuclear receptor transcriptional regulatory complex
Authors: Asahina Masako , Thurtle-Schmidt Deborah , Yamamoto Keith R. 
Published: March 2020

ABSTRACTMetazoan transcriptional regulatory factors (TFs) bind to genomic response elements and assemble with co-regulators into transcriptional regulatory complexes (TRCs) whose composition, structure and activities are gene-, cell- and physiological-context specific. Each TRC is a “regulatory logic module,” integrating incoming signaling information, which defines context and thereby recruits a distinct combination of co-regulators that together specify outgoing regulatory activity. Analyzing TRCs unique to every context is daunting, yet justified by their properties as self-contained regulatory modules. As proof-of-concept, we performed a forward genetic screen inC. eleganscarrying a synthetic simple response element for nuclear receptor NHR-25 upstream of a fluorescent reporter gene. We isolated independent mutations inuba-2, a component of the sumoylation signaling machinery, and inlir-2, which we demonstrated to be a novel co-regulator, interacting with NHR-25 through LxxLL motifs and modulating target gene expression. Our studies establish that an unbiased genetic screen readily identifies both afferent and efferent components that specify TRC function, and suggest that screening natural response elements of interest could illuminate molecular mechanisms of both context-specificity and transcriptional regulation.
Imperative role of particulate matter in innate immunity during RNA virus infection
Authors: Mishra Richa , Pandikannan K , Gangamma S , Raut Ashwin Ashok , Kumar Himanshu 
Published: March 2020

ABSTRACTSensing of pathogens by specialized receptors is the hallmark of the innate immune response. Innate immune response also mounts a defense response against various allergens and pollutants including particulate matter present in the atmosphere. Air pollution has been included as the top threat to global health declared by WHO which aims to cover more than three billion people against health emergencies from 2019-2023. Particulate matter (PM), one of the major components of air pollution, is a significant risk factor for many human diseases and its adverse effects include morbidity and premature deaths throughout the world. Several clinical and epidemiological studies have identified a key link between the PM composition and the prevalence of respiratory and inflammatory disorders. However, the underlying molecular mechanism is not well understood. Here, we investigated the influence of air pollutant, PM10during RNA virus infections using highly pathogenic avian influenza (HPAI). We thus characterized the transcriptomic profile of lung epithelial cell line, A549 treated with PM10prior to infection with (HPAI) H5N1 influenza virus, which is known to severely affect the lung and cause respiratory damage. We found that PM10regulates virus infectivity and enhances overall pathogenic burden in the lung cells. Additionally, the transcriptomic profile highlights the connection of host factors related to various metabolic pathways and immune responses which were dysregulated during virus infection. Overall our findings suggest a strong link between the prevalence of respiratory illness and the air quality.
Genomic evidence for recurrent genetic admixture during domestication mediterranean olive trees (Olea europaea)
Authors: Julca Irene , Marcet-Houben Marina , Cruz Fernando , Gómez-Garrido Jèssica , Gaut Brandon S. , Díez Concepción M. , Gut Ivo G. , Alioto Tyler S. , Vargas Pablo , Gabaldón Toni 
Published: March 2020

AbstractBackgroundThe olive tree (Olea europaeaL. subsp.europaea, Oleaceae) has been the most economic perennial crop for Mediterranean countries since its domestication around 6,000 years ago. Two taxonomic varieties are currently recognized: cultivated (var.europaea) and wild (var.sylvestris) trees. To shed light into the recent evolution and domestication of the olive tree, we sequenced the genomes of twelve individuals: ten var.europaea, one var.sylvestris, and one outgroup taxon (subsp.cuspidata). All of them were analysed together with an improved assembly of var.europaeareference genome and the available assembly of var.sylvestris.ResultsOur analyses show that cultivated olives exhibit slightly lower levels of overall genetic diversity than wild forms, and that this can be partially explained by the occurrence of a mild population bottleneck 5000-7000 years ago during the primary domestication period. We also provide the first phylogenetic analysis of genome-wide sequences, which supports a continuous process of domestication of the olive tree. This, together with population structure and introgression analyses highlights genetic admixture with wild populations across the Mediterranean Basin in the course of domestication.ConclusionsAltogether, our results suggest that a primary domestication area in the eastern Mediterranean basin was followed by numerous secondary events across most countries of southern Europe and northern Africa, often involving genetic admixture with genetically rich wild populations, particularly from the western Mediterranean Basin. Based on selection tests and a search for selective sweeps, we found that genes associated with stress response and developmental processes were positively selected in cultivars. However, we did not find evidence that genes involved in fruit size or oil content were under positive selection.
Conserved luminal C-terminal domain dynamically controls interdomain communication in sarcolipin
Authors: Aguayo-Ortiz Rodrigo , Fernández-de Gortari Eli , Espinoza-Fonseca L. Michel 
Published: March 2020

ABSTRACTSarcolipin (SLN) mediates Ca2+ transport and metabolism in muscle by regulating the activity of the Ca2+ pump SERCA. SLN has a conserved luminal C-terminal domain that contributes to the its functional divergence among homologous SERCA regulators, but the precise mechanistic role of this domain remains poorly understood. We used all-atom molecular dynamics (MD) simulations of SLN totaling 77.5 μs to show that the N- (NT) and C-terminal (CT) domains function in concert. Analysis of the MD simulations showed that serial deletions of SLN C-terminus does not affect the stability of the peptide nor induce dissociation of SLN from the membrane but promotes a gradual decrease in both tilt angle of the transmembrane helix and the local thickness of the lipid bilayer. Mutual information analysis showed that the NT and CT domains communicate with each other in SLN, and that interdomain communication is partially or completely abolished upon deletion of the conserved segment Tyr29-Tyr31 as well as by serial deletions beyond this domain. Phosphorylation of SLN at residue Thr5 also induces changes in the communication between the CT and NT domains, thus providing additional evidence for interdomain communication within SLN. We found that interdomain communication is independent of the force field used and lipid composition, thus demonstrating that communication between the NT and CT domains is an intrinsic functional feature of SLN. We propose the novel hypothesis that the conserved C-terminus is an essential element required for dynamic control of SLN regulatory function.Abstract Figure
Identification and characterization of diverse OTU deubiquitinases in bacteria
Authors: Schubert Alexander F. , Nguyen Justine V. , Franklin Tyler G. , Geurink Paul P. , Roberts Cameron G. , Sanderson Daniel J. , Miller Lauren N. , Ovaa Huib , Hofmann Kay , Pruneda Jonathan N. , Komander David 
Published: March 2020

ABSTRACTManipulation of host ubiquitin signaling is becoming an increasingly apparent evolutionary strategy among bacterial and viral pathogens. By removing host ubiquitin signals, for example, invading pathogens can inactivate immune response pathways and evade detection. The Ovarian Tumor (OTU) family of deubiquitinases regulates diverse ubiquitin signals in humans. Viral pathogens have also extensively co-opted the OTU fold to subvert host signaling, but the extent to which bacteria utilize the OTU fold was unknown. We have predicted and validated a set of OTU deubiquitinases encoded by several classes of pathogenic bacteria. Biochemical assays highlight the ubiquitin and polyubiquitin linkage specificities of these bacterial deubiquitinases. By determining the ubiquitin-bound structures of two examples, we demonstrate the novel strategies that have evolved to both thread an OTU fold and to recognize a ubiquitin substrate. With these new examples, we perform the first cross-kingdom structural analysis of the OTU fold that highlights commonalities among distantly-related OTU deubiquitinases.
An optogenetic switch for the Set2 methyltransferase provides evidence for rapid transcription-dependent and independent dynamics of H3K36 methylation
Authors: Lerner Andrew M. , Hepperla Austin J. , Keele Gregory R. , Meriesh Hashem , Yumerefendi Hayretin , Restrepo David , Zimmerman Seth , Bear James , Kuhlman Brian , Davis Ian J. , Strahl Brian D. 
Published: March 2020

ABSTRACTHistone H3 lysine 36 methylation (H3K36me) is a conserved histone modification associated with transcription and DNA repair. Although the effects of H3K36 methylation have been studied, the short-term genome-wide dynamics of H3K36me deposition and removal are not known. We established rapid and reversible optogenetic control for Set2, the sole H3K36 methyltransferase in yeast, by fusing the enzyme with the light activated nuclear shuttle (LANS) domain. Early H3K36me3 dynamics identified rapid methylationin vivo, with total H3K36me3 levels correlating with RNA abundance. Although genes exhibited disparate levels of H3K36 methylation, relative rates of H3K36me3 accumulation were largely linear and consistent across genes, suggesting a rate-limiting mechanism for H3K36me3 deposition. Removal H3K36me2/3 was also rapid and highly dependent on the demethylase Rph1. However, the per-gene rate of H3K36me3 loss weakly correlated with RNA abundance and followed exponential decay, suggesting H3K36 demethylases act in a global, stochastic manner.
Population structure and pharmacogenomic risk stratification in the United States
Authors: Nagar Shashwat Deepali , Conley Andrew B. , King Jordan I. 
Published: March 2020

AbstractPharmacogenomic (PGx) variants mediate how individuals respond to medication, and response differences among racial/ethnic groups have been attributed to patterns of PGx diversity. We hypothesized that genetic ancestry (GA) would provide higher resolution for stratifying PGx risk, since it serves as a more reliable surrogate for genetic diversity than self-identified race/ethnicity (SIRE), which includes a substantial social component. We analyzed a cohort of 8,628 individuals from the United States (US), for whom we had both SIRE information and whole genome genotypes, with a focus on the three largest SIRE groups in the US: White, Black, and Hispanic. Whole genome genotypes were used to characterize individuals’ continental ancestry fractions – European, African, and Native American – and individuals were grouped according to their GA profiles. SIRE and GA groups were found to be highly concordant. Continental ancestry predicts individuals’ SIRE with >96% accuracy, and accordingly GA provides only a marginal increase in resolution for PGx risk stratification. PGx variants are highly diverged compared to the genomic background; 82 variants show significant frequency differences among SIRE groups, and genome-wide patterns of PGx variation are almost entirely concordant with SIRE. Nevertheless, 97% of PGx variation is found within rather than between groups. Examples of highly differentiated PGx variants illustrate how SIRE partitions PGx variation based on group-specific ancestry patterns and contains valuable information for risk stratification. Finally, we show that individuals who identify as Black or Hispanic benefit more when SIRE is considered for treatment decisions than individuals from the majority White population.
Predicting Molecular Fingerprint from Electron−Ionization Mass Spectrum with Deep Neural Networks
Authors: Ji Hongchao , Lu Hongmei , Zhang Zhimin 
Published: April 2020

AbstractElectron−ionization mass spectrometry (EI-MS) hyphenated gas chromatography (GC) is the workhorse to analyze volatile compounds in complex samples. The spectral matching method can only identify compounds within spectral database. In response, we present a deep-learning-based approach (DeepEI) for structure elucidation of unknown compound with its EI-MS spectrum. DeepEI employs deep neural networks to predict molecular fingerprint from EI-MS spectrum, and searches molecular structure database with the predicted fingerprints. In addition, a convolutional neural network was also trained to filter the structures in database and improve the identification performance. Our method shows improvement on the competing method NEIMS in identification accuracy on both NIST test dataset and MassBank dataset. Furthermore, DeepEI (spectrum to fingerprint) and NEIMS (fingerprint to spectrum) can be combined to improve identification accuracy.
Host-dependent differences in replication strategy of theSulfolobusSpindle-shaped Virus strain SSV9 (a.k.a., SSVK1): Lytic replication in hosts of the family Sulfolobaceae
Authors: Ceballos Ruben Michael , Drummond Coyne , Stacy Carson Len , Crespo Elizabeth Padilla , Stedman Kenneth 
Published: April 2020

ABSTRACTTheSulfolobusSpindle-shaped Virus (SSV) system has become a model for studying thermophilic virus biology, including archaeal host-virus interactions and biogeography. Several factors make the SSV system amenable to studying archaeal genetic mechanisms (e.g., CRISPRs) as well as virus-host interactions in high temperature acidic environments. First, it has been shown that endemic populations ofSulfolobus, the reported SSV host, exhibit biogeographic structure. Second, the acidic (pH<4.5) high temperature (65-88°C) SSV habitats have low biodiversity, thus, diminishing opportunities forhost switching. Third, SSVs and their hosts are readily cultured in liquid media and on gellan gum plates. Fourth, given the wide geographic separation between the variousSSV-Sulfolobushabitats, the system is amenable for studying allopatric versus sympatric virus-host interactions. Previously, we reported that SSVs exhibit differential infectivity on allopatric and sympatric hosts. We also noticed a wide host range for virus strain SSV9 (a.k.a., SSVK1). For decades, SSVs have been described as “non-lytic” dsDNA viruses that infect species of the genusSulfolobusand release virions via “blebbing” or “budding” as a preferred strategy over host lysis. Here, we show that SSVs infect more than one genus of the family Sulfolobaceae and, in allopatric hosts, SSV9 does not appear to release virions by blebbing. Instead, SSV9 appears to lyse all susceptible allopatric hosts tested, while exhibiting canonical non-lytic viral release via “blebbing” (historically reported for all other SSVs), on a single sympatric host. Lytic versus non-lytic virion release does not appear to be driven by multiplicity of infection (MOI). Greater relative stability of SSV9 compared to other SSVs (i.e., SSV1) in high temperature, low pH environments may contribute to higher transmission rates. However, neither higher transmission rate nor relative virulence in SSV9 infection drives replication profile (i.e., lytic versus non-lytic) in susceptible hosts. Although it is known that CRISPR-Cas systems offer protection against viral infection in prokaryotes, CRISPRS are not reported to be a determinant virus replication strategy. Thus, the genetic/molecular mechanisms underlying SSV9-induced lysis are unknown. These results suggest that there are unknown genetic elements, resulting from allopatric evolution, that drive virion release strategy in specific host strain-SSV strain pairings.
Fast Cell Parasites Detection with Neural Networks
Authors: Xu X. F. , Talbot S. , Lu S. B. , Selvaraja T. 
Published: April 2020

AbstractDeep learning has dramatically improved the performance in many application areas such as image classification, object detection, speech recognition, drug discovery and etc since 2012. Where deep learning algorithms promise to discover the intricate hidden information inside the data by leveraging the large dataset, advanced model and computing power. Although deep learning techniques show medical expert level performance in a lot of medical applications, but some of the applications are still not explored or under explored due to the variation of the species. In this work, we studied the bright field based cell level Cryptosporidium and Giardia detection in the drink water with deep learning. Our experimental demonstrates that the new developed deep learning-based algorithm surpassed the handcrafted SVM based algorithm with above 97 percentage in accuracy and 700+fps in speed on embedded Jetson TX2 platform. Our research will lead to real-time and high accuracy label-free cell level Cryptosporidium and Giardia detection system in the future.
Analysis of the Worldwide Corona Virus (COVID-19) Pandemic Trend; A Modelling Study to Predict Its Spread
Authors: Qasim Muhammad , Ahmad Waqas , Yoshida Minami , Gould Maree , Yasir Muhammad 
Published: April 2020

AbstractObjectiveThe Coronavirus (COVID-19) has advanced into 197 countries and territories leaving behind a total of 372,757 confirmed cases and 16231 deaths.MethodsOne the basis of WHO situation reports data of COVID-19 along with daily official reports from the Japan, China and the Kore we modelled the spread of COVID19 by using the Successive Approximation Method. We defined the two state of data to find the mean ratio (η) of the present cases count to the sum of previous and present cases. This ratio further predicts the future state of COVID-19 pandemic.ResultsThe mean ratio (η) of expected cases were found 0.485, while the mean ratio for deaths was found to be 0.49. We calculated worldwide expected lower bound value for confirmed cases 247007 cases with maximum limit of 1667719 cases and minimum deaths count 8660 with upper limit of 117397 deaths in next 30 days. While in the case of Iran, a large increase in the number of deaths are expected in the upcoming 30 days with lower bound value of 1140 deaths and maximum value of 598478 deaths.InterpretationIran whole population is on risk.
Collapse of the hepatic gene regulatory network in the absence of FoxA factors
Authors: Reizel Yitzhak , Morgan Ashleigh , Gao Long , Lan Yemin , Manduchi Elisabetta , Waite Eric L. , Wang Amber W. , Wells Andrew , Kaestner Klaus H. 
Published: April 2020

AbstractThe FoxA transcription factors are critical for liver development through their pioneering activity, which initiates a highly complex regulatory network thought to become progressively resistant to the loss of any individual hepatic transcription factor via mutual redundancy. To investigate the dispensability of FoxA factors for maintaining this regulatory network, we ablated all FoxA genes in the adult mouse liver. Remarkably, loss of FoxA caused rapid hepatocyte dedifferentiation manifested by a massive reduction in the expression of key liver genes. Interestingly, expression of these genes was reduced back to the low levels of the fetal prehepatic endoderm stage, leading to necrosis and lethality within days. Mechanistically, we found FoxA proteins to be required for maintaining enhancer activity, chromatin accessibility, nucleosome positioning and binding by HNF4α. Thus, the FoxA factors act continuously, guarding hepatic enhancer activity throughout life.
Glucosylhydroxyceramides Modulate Secretion Machinery of a Subset of Plasmodesmata Proteins and a Change in the Callose Accumulation
Authors: Iswanto Arya Bagus Boedi , Shon Jong Cheol , Vu Minh Huy , Kumar Ritesh , Liu Kwang Hyeon , Kim Jae-Yean 
Published: April 2020

AbstractThe plasma membranes encapsulated in the plasmodesmata (PDs) with symplasmic nano-channels contain abundant lipid rafts, which are enriched by sphingolipids and sterols. The attenuation of sterol compositions has demonstrated the role played by lipid raft integrity in the intercellular trafficking of glycosylphosphatidylinositol (GPI)-anchored PD proteins, particularly affecting in the callose enhancement. The presence of callose at PD is tightly attributed to the callose metabolic enzymes, callose synthases (CalSs) and β-1,3-glucanases (BGs) in regulating callose accumulation and callose degradation, respectively. Sphingolipids have been implicated in signaling and membrane protein trafficking, however the underlying processes linking sphingolipid compositions to the control of symplasmic apertures remain unknown. A wide variety of sphingolipids in plants prompts us to investigate which sphingolipid molecules are important in regulating symplasmic apertures. Here, we demonstrate that perturbations of sphingolipid metabolism by introducing several potential sphingolipid (SL) pathway inhibitors and genetically modifying SL contents from two independent SL pathway mutants are able to modulate callose deposition to control symplasmic connectivity. Our data from pharmacological and genetic approaches show that the alteration in glucosylhydroxyceramides (GlcHCers) particularly disturb the secretory machinery for GPI-anchored PdBG2 protein, resulting in an over accumulated callose. Moreover, our results reveal that SL-enriched lipid rafts link symplasmic channeling to PD callose homeostasis by controlling the targeting of GPI-anchored PdBG2. This study elevates our understanding of the molecular linkage underlying intracellular trafficking and precise targeting to specific destination of GPI-anchored PD proteins incorporated with GlcHCers contents.