bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data-driven large-scale genomic analysis reveals an intricate phylogenetic and functional landscape in J-domain proteins
Authors: Malinverni Duccio , Zamuner Stefano , Rebeaud Mathieu E. , Barducci Alessandro , Nillegoda Nadinath B. , De Los Rios Paolo 
Published: March 2022

AbstractThe 70 kDalton Heat shock protein (Hsp70) chaperone system is emerging as a central hub of the proteostasis network that helps maintain protein homeostasis in all organisms. The recruitment of Hsp70 to perform a vast array of different cellular functions is regulated by a family of co-chaperones known as J-domain proteins (JDP) that bear a small namesake J-domain, which is required to interact and drive the ATPase cycle of Hsp70s. Both prokaryotic and eukaryotic JDPs display staggering diversity in domain architecture (besides the ubiquitous J-domain), function, and cell localization. On the contrary, a relatively small number of Hsp70 paralogs exist in cells, suggesting a high degree of specificity, but also promiscuity, in the partnering between JDPs and Hsp70s. Very little is known about the JDP family, despite their essential role in cellular proteostasis, development, and the link to a broad range of human diseases. The number of JDP gene sequences identified across all kingdoms as a consequence of advancements in sequencing technology has exponentially increased, where it is now beyond the ability of careful manual curation. In this work, we first provide a broad overview of the JDP repertoire accessible from public databases, and then we use an automated classification scheme, based on Artificial Neural Networks (ANNs), to demonstrate that the sequences of J-domains carry sufficient discriminatory information to recover with high reliability the phylogeny, localization, and domain composition of the corresponding full-length JDP. By harnessing the interpretability of the ANNs, we find that many of the discriminatory sequence positions match to residues that form the interaction interface between the J-domain and Hsp70. This reveals that key residues within the J-domains have coevolved with their obligatory Hsp70 partners to build chaperone circuits for specific functions in cells.
Organism-wide mapping of MHC class I and II expression in mouse lemur cells and tissues
Authors: Guethlein Lisbeth A. , Ezran Camille , Liu Shixuan , Krasnow Mark A. , Parham Peter 
Published: March 2022

ABSTRACTThe major histocompatibility complex (MHC) class I and II glycoproteins have been associated with numerous disease phenotypes, mechanisms and outcomes. These associations can be due to allotypic polymorphism or to altered levels of allotype expression. Although well studied in a range of cell types and microenvironments, no study has encompassed all cell-types present in an individual mouse lemur. In this study the droplet-based single cell RNA sequence data from the mouse lemur cell atlas, Tabula Microcebus, were used to examine the patterns of MHC class I and II expression. The cell atlas comprises data obtained from 27 organs from four mouse lemurs, enabling comparison of expression pattern between both cell types and the individual lemurs. Patterns of gene expression showed a good concordance among the four mouse lemurs. Three primary patterns of expression were identified and associated with different cell-types. Mapping MHC expression onto existing cell trajectories of cell development and spatial gradients revealed fine scale differences in expression level and pattern in single tissues. The bioinformatic pipeline developed here is applicable to other cell atlas projects.
A parametric logistic equation with light flux and medium concentration for cultivation planning of microalgae
Authors: Kambe Kazuki , Hirokawa Yasutaka , Koshi Asuka , Hori Yutaka 
Published: March 2022

AbstractMicroalgae are considered to be promising producers of bioactive chemicals, feeds, and fuels from carbon dioxide by photosynthesis. Thus, the prediction of microalgal growth profiles is important for the planning of cost-effective and sustainable cultivation-harvest cycles. This paper proposes a mathematical model capable of predicting the effect of light flux into culture and medium concentration on the growth profiles of microalgae by incorporating these growth-limiting factors into the logistic equation. The specific form of the equation is derived based on the experimentally measured growth profiles of Monoraphidium sp., a microalgal strain isolated by the authors, under 16 conditions consisting of the combinations of incident light fluxes into culture and initial medium concentrations. Using a cross-validation method, it is shown that the proposed model has the ability to predict necessary incident light flux into culture and initial medium concentration for harvesting target biomass at target time. Finally, the model-guided cultivation planning is performed and is evaluated by comparing the result with the experimental data.
Diversity of sex chromosomes in Sulawesian medaka fishes
Authors: Ansai Satoshi , Montenegro Javier , Masengi Kawilarang W.A. , Nagano Atsushi J. , Yamahira Kazunori , Kitano Jun 
Published: March 2022

AbstractRecent genetic and genomic studies have revealed tremendous diversity in sex chromosomes across diverse taxa. Although theoretical studies predict that sex chromosome evolution can drive the evolution of sexual dimorphism, empirical studies are still limited. A taxonomic group that shows diversity in both sex chromosomes and sexual dimorphism provides excellent opportunity to investigate the link between the evolution of sex chromosomes and sexual dimorphism. The medaka fishes (family Adrianichthyidae) exhibit both rapid sex chromosome turnovers and diversification of sexually dimorphic traits. In the present study, we investigated the sex chromosomes of 13 Oryzias species from Sulawesi, Indonesia, that have diversified in sexual dichromatism. Using pooled sequencing we found sex chromosomes in 9 species that all had XY systems, with a few species being possibly modified by multiple loci. Seven species (O. woworae, O. asinua, O. wolasi, O. matanensis, O. celebensis, O. hadiatyae, and O. dopingdopingensis) share linkage group (LG) 24 as sex chromosomes; however, they differed in the length and magnitude of sequence divergence between the X and Y chromosomes. The sex chromosome of O. eversi was LG4, which has not been reported as a sex chromosome in any other medaka species. In O. sarasinorum, LG16 and LG22 are associated with sex. Although LG16 was found to be sex-linked in another medaka species previously examined, the sex-determining regions did not overlap. Frequent turnovers and the great diversity of the sex chromosomes make Sulawesian medaka species a model system for investigating the roles of sex chromosome evolution in the diversification of sexual dimorphism.
Psilocybin induces spatially constrained alterations in thalamic functional organizaton and connectivity
Authors: Gaddis Andrew , Lidstone Daniel E. , Nebel Mary Beth , Griffiths Roland , Mostofsky Stewart H. , Mejia Amanda , Barrett Frederick 
Published: March 2022

ABSTRACTBackgroundSerotonin 2A receptor (5-HT2AR) agonist psychedelics including psilocybin and LSD (“classic” psychedelics) evoke acute alterations in perception and cognition. Altered thalamocortical connectivity has been proposed to underlie these effects, which is supported by some functional MRI (fMRI) studies. Likely due to sample size limitations, these studies have treated the thalamus as a unitary structure, despite known differential 5-HT2ARexpression and functional specificity of different intrathalamic nuclei. Independent Component Analysis (ICA) has been employed to generate functional subdivisions of the thalamus from resting state fMRI (rsfMRI) data. This report utilizes a novel data-sparing ICA approach in order to examine psilocybin-induced changes in intrathalamic functional organization and thalamocortical connectivity.MethodsBaseline rsfMRI data (n=38) was utilized to generate a template, which was then applied in a novel ICA-based analysis of the acute effects of psilocybin on intra- and extra-thalamic functional organization and connectivity in a smaller sample (n=18). Correlations with subjective reports of drug effect and comparisons with a previously reported analytic approach (treating the thalamus as a single functional unit) were conducted.ResultsSeveral intrathalamic components showed significant psilocybin-induced alterations in intrathalamic spatial organization, largely localized to the mediodorsal and pulvinar nuclei, and correlated with reported subjective effects. These same components demonstrated alterations in thalamocortical connectivity, largely with visual and default mode networks. Analysis in which the thalamus is treated as a singular unitary structure showed an overall numerical increase in thalamocortical connectivity, consistent with previous literature using this approach, but this increase did not reach statistical significance.ConclusionsUtilization of a novel analytic approach demonstrated changes in intra- and extra-thalamic functional organization and connectivity of intrathalamic nuclei and cortical networks known to express the 5-HT2AR. Given that these changes were not observed using whole-thalamus analyses, it seems that psilocybin may cause widespread but modest increases in thalamocortical connectivity that are offset by strong focal decreases in functionally relevant intrathalamic nuclei.
P4HA2: A link between tumor-intrinsic hypoxia, partial EMT and collective migration
Authors: Aggarwal Vaishali , Sahoo Sarthak , Donnenberg Vera S. , Chakraborty Priyanka , Jolly Mohit Kumar , Sant Shilpa 
Published: March 2022

AbstractEpithelial-to-mesenchymal transition (EMT), a well-established phenomenon studied across pan-cancer types, has long been known to be a major player in driving tumor invasion and metastasis. Recent studies have highlighted the importance of partial EMT phenotypes in metastasis [1]. Initially thought as a transitional state between epithelial and mesenchymal phenotypic states, partial EMT state is now widely recognized as a key driver of intra-tumoral heterogeneity and phenotypic plasticity, further accelerating tumor metastasis and therapeutic resistance. However, how tumor microenvironments regulate partial EMT phenotypes remains unclear. We have developed unique size-controlled three-dimensional microtumor models that recapitulate tumor-intrinsic hypoxia and the emergence of collectively migrating cells. In this study, we further interrogate these microtumor models to understand how tumor-intrinsic hypoxia regulates partial EMT and collective migration in hypoxic large microtumors fabricated from T47D breast cancer cells. We also compared global gene expression profiles of hypoxic, migratory microtumors to that of non-hypoxic, non-migratory microtumors at early and late time-points. Using our microtumor models, we identified unique gene signatures for tumor-intrinsic hypoxia (early versus late), partial EMT and migration (pre-migratory versus migratory phenotype). Through differential gene expression analysis between the microtumor models with an overlap of hypoxia, partial EMT and migration signatures, we identified prolyl 4-hydroxylase subunit 2 (P4HA2), a hypoxia responsive gene, as a central regulator common to hypoxia, partial EMT and collective migration. Further, the inhibition of P4HA2 significantly blocked collective migration in hypoxic microtumors. Thus, using the integrated computational-experimental analysis, we identify the key role of P4HA2 in tumor-intrinsic hypoxia-driven partial EMT and collective migration.
Case Study of Single-cell Protein Activity Based Drug Prediction for Precision Treatment of Cholangiocarcinoma
Authors: Obradovic Aleksandar , Tomassoni Lorenzo , Yu Daoqi , Guillan Kristina , Souto Katie , Fraser Elise , Bates Susan , Drake Charles G. , Saenger Yvonne , Cruz Filemon Dela , Kung Andrew , Califano Andrea 
Published: March 2022

AbstractCholangiocarcinoma is a rare, aggressive malignancy with limited treatment options, due to a paucity of actionable mutations and low response to immune checkpoint inhibitors. Furthermore, its extreme heterogeneity prevents identification of actionable dependencies from bulk-tissue profiles. To address these challenges, we introduce a highly generalizable, single-cell framework for the mechanism-based prioritization of drugs to treat rare, highly heterogeneous tumors. Analysis of transformed cells, accounting for only 10% of a cholangiocarcinoma patient biopsy revealed three molecularly-distinct subpopulations, predicted to be sensitive to four drugs by regulatory network-based analysis. Validation in a low-passage, patient-derived xenograft (PDX) from the same patient confirmed tumor growth rate control by two of these drugs (plicamycin and dacinostat) and further validated predicted subpopulation-specific effects, suggesting they may represent promising candidates for follow-up clinical trials, either alone or in combination with current standard-of-care chemotherapies. The proposed approach can be generalized to elucidate complementary dependencies of rare, heterogeneous tumors, at the single cell level.
A Standardized Framework for Taxonomy Analysis in Bacterial Kingdom based on Protein Domain
Authors: Wang Boqian , Zhou Jianglin , Jin Yuan , Hu Mingda , Zhao Yunxiang , Wang Xin , Liang Long , Yue Junjie , Ren Hongguang 
Published: March 2022

AbstractThe taxonomy research on the bacterial kingdom is important and can be usually conducted by the analysis on conserved genes, 16s rRNA, protein domain, and so on. Comparatively, the protein domains maintain a most direct relationship with phenotypes. In this paper, based on the protein domain, we propose a 3-step framework to standardize the classification process of bacteria. Different model candidates are involved and discussed in each step. By comparing the classification results with existing taxonomy, we select the most appropriate candidate to improve the framework, and furthermore, discuss their biological significance. Finally, we put forward taxonomy suggestions based on the best classification results.ImportanceWe standardize a 3-step framework to carry out bacterial taxonomy research based on protein domain. Furthermore, we filter out the best solution in each step that can together generate the most appropriate classification result, and at the same time, we discuss the biological significant it indicates. Finally, we propose suggestions on NCBI bacterial taxonomy based on the classification results.
Development of a vocal biomarker for fatigue monitoring in people with COVID-19
Authors: Elbéji Abir , Zhang Lu , Higa Eduardo , Fischer Aurélie , Despotovic Vladimir , Nazarov Petr V. , Aguayo Gloria A. , Fagherazzi Guy 
Published: March 2022

AbstractObjectiveTo develop a vocal biomarker for fatigue monitoring in people with COVID-19.DesignProspective cohort study.SettingPredi-COVID data between May 2020 and May 2021.ParticipantsA total of 1772 voice recordings was used to train an AI-based algorithm to predict fatigue, stratified by gender and smartphone’s operating system (Android/iOS). The recordings were collected from 296 participants tracked for two weeks following SARS-CoV-2 infection.primary and secondary outcome measuresFour machine learning algorithms (Logistic regression, k-nearest neighbors, support vector machine, and soft voting classifier) were used to train and derive the fatigue vocal biomarker. A t-test was used to evaluate the distribution of the vocal biomarker between the two classes (Fatigue and No fatigue).ResultsThe final study population included 56% of women and had a mean (±SD) age of 40 (±13) years. Women were more likely to report fatigue (P<.001). We developed four models for Android female, Android male, iOS female, and iOS male users with a weighted AUC of 79%, 85%, 86%, 82%, and a mean Brier Score of 0.15, 0.12, 0.17, 0.12, respectively. The vocal biomarker derived from the prediction models successfully discriminated COVID-19 participants with and without fatigue (t-test P<.001).ConclusionsThis study demonstrates the feasibility of identifying and remotely monitoring fatigue thanks to voice. Vocal biomarkers, digitally integrated into telemedicine technologies, are expected to improve the monitoring of people with COVID-19 or Long-COVID.
Impact and cost-effectiveness of frequent HIV re-testing among key populations in Viet Nam: a modeling study
Authors: Green Dylan , Coomes David , Barnabas Ruanne V. , Sharma Monisha , Barr-Dichiara Magdalena , Jamil Muhammad S. , Owiredu Morkor Newman , Macdonald Virginia , Nguyen Van , Hai Son Vo , Wi Theodora E. , Johnson Cheryl , Drake Alison L. 
Published: March 2022

ABSTRACTBackgroundHIV testing and counseling is a key component of HIV prevention and the entry point into the treatment cascade, which improves for individual clinical outcomes and reduces onward HIV transmission. Current guidelines recommend at least annual testing for key populations. More frequent testing could provide health benefits, but these additional services increase the program the cost-effectiveness is not well-evaluated.MethodsWe used a compartmental mathematical model to simulate the health and economic impact of HIV testing one to four times per year for men who have sex with men, people who inject drugs, and female sex workers in Viet Nam. Model outcomes included costs, HIV infections, HIV-related deaths, and disability-adjusted life years (DALYs) associated with each scenario. We used an opportunity cost-based cost-effectiveness threshold of US $2,255 per DALY averted, discounted costs and health benefits at 3% annually, and used a time horizon from 2021 to 2030 to calculate incremental cost-effectiveness ratios (ICERs).ResultsCompared to the baseline scenario, more frequent HIV testing was estimated to incrementally avert 10.2%, 5.2%, 3.0%, and 1.6% discounted infections for one-, two-, three-, and four-tests per year, respectively. ICERs associated with each scenario ranged from $464, $1,190, $1,762, and $2,727 per DALY averted for one-, two-, three-, and four-tests per year, respectively.ConclusionsIncreased HIV testing frequency for key populations was projected to avert HIV incidence, mortality, and disability in Viet Nam and was cost-effective. Settings with a similar context should consider strategies on how to optimize retesting among key populations.
Treatment Outline and Clinical Outcome of Hospitalized COVID-19 Patients: Experiences from a Combined Military Hospital of Bangladesh
Authors: Mahboob Sabiha , Johora Fatema , Abbasy Asma Akter , Jeenia FatihaTasmin , Ali Mohammad , Kabir Md Humayun , Sojib Ferdaush Ahmed , Ferdoush Jannatul 
Published: March 2022

ABSTRACTBackgroundGlobal knowledge of treatment and outcomes of COVID-19 has been evolving since the onset of the pandemic.Materials and MethodsThe objective of this cross-sectional study was to explore treatment and outcome of COVID-19 patients admitted in a Combined Military Hospital of Bangladesh. Data were collected from treatment records of patients of the CMH Bogura during the period of June 2020 to August 2020. Total 219 RT-PCR positive admitted patients were included as study population.ResultAmong 219 patients, 78.6% were male and 21.5% were female, mean age of patients was 34.3 ± 12.2. About14.6% patients had one or more comorbidities. Most (83.1%) of the admitted patients were diagnosed as mild cases. Antimicrobials were used in 98.8% cases, and frequent use of doxycycline (80.4%) and ivermectine (77.2%) was found. Anticoagulant and steroid therapy were used in 42.0% and 15.5% patients respectively. O2 therapy was required in 6.0% cases and intensive care unit (ICU) support was needed in 2.3% cases.Duration of hospital stay was 12.1± 4.4 days and 100% of patients were discharged from hospital. There was no single mortality during the study period.ConclusionHigh prevalence of antimicrobials use was observed among the hospitalized COVID-19 patients in this single center study.Supportive care was effective with no incidence of mortality.
APOEε4 and exercise interact to influence systemic and cerebral risk factors for dementia
Authors: Foley Kate E. , Diemler Cory A. , Hewes Amanda A. , Garceau Dylan T. , Sasner Michael , Howell Gareth R. 
Published: March 2022

AbstractINTRODUCTIONAPOEε4 is the strongest genetic risk factor for Alzheimer’s disease and related dementias (ADRDs) affecting many different pathways that lead to cognitive decline. Exercise is one of the most widely proposed prevention, and intervention strategies to mitigate risk and symptomology of ADRDs. Importantly, exercise and APOEε4 affect similar processes on the body and brain. While both APOEε4, and exercise have been studied extensively, their interactive effects are not well understood.METHODSTo address this, male and female APOEε3/ε3, APOEε3/ε4 and APOEε4/ε4 mice ran voluntarily from wean (1mo) to midlife (12mo). Longitudinal and cross-sectional phenotyping was performed on the periphery and the brain, on markers of risk for dementia such as weight, body composition, circulating cholesterol composition, activities of daily living, energy expenditure, and cortical and hippocampal transcriptional profiling.RESULTSData revealed chronic running decreased age-dependent weight gain, lean and fat mass, and serum LDL concentration dependent on APOE genotype. Additionally, murine activities of daily living and energy expenditure were significantly influenced by an interaction between APOE genotype and running in both sexes. Transcriptional profiling of the cortex and hippocampus predicted that APOE genotype and running interact to affect numerous biological processes including vascular integrity, synaptic/neuronal health, cell motility, and mitochondrial metabolism, in a sex-specific manner.DISCUSSIONThese data provide compelling evidence that APOE genotype should be considered for population-based strategies that incorporate exercise to prevent ADRDs.
Speeded Inference Game: Opening a new chapter in the assessment of error awareness
Authors: Niessen Eva , Wickert Jonas , Schober Martin , Fink Gereon R. , Stahl Jutta , Weiss Peter H. 
Published: March 2022

AbstractInfluential theories on error processing assume that when we conduct errors adaptive processes are triggered to improve our behaviour and prevent errors in the future. These processes appear to be more effective after participants have detected an error. Therefore, the assessment of error awareness allowing a differential analysis of detected and undetected errors in the context of cognitive control and behavioural adjustments has gained more and more attention in the past decades. A common methodological challenge posed on all studies investigating error detection is that the number of undetected errors is usually relatively low.Here, we introduce a gamified experimental task that uses an adaptive algorithm to generate a robust and stable amount of errors with a high rate of undetected errors. Further, we were able to identify error types, which interestingly differed in terms of their detection rate. Moreover, the game-like appearance of the novel experimental task led to highly motivated participants. The results of the first study were replicated and extended by a second behavioural study. Notably, in study 2, a change in task design specifically modulated error detection, while these changes did not affect the total error rate.Potential applications of the open-source code will be discussed. With this newly developed paradigm, we wish to lay the ground for future research to understand better (neural) processes associated with error awareness.