bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of intron-1 of odorant-binding protein-1 of Anopheles stephensi as a marker for the identification of biological forms or putative sibling species
Authors: Singh Om P. , Mishra Shobhna , Sharma Gunjan , Sindhania Ankita , Kaur Taranjeet , Sreehari U. , Das Manoj K. , Kapoor Neera , Gupta Bhavna 
Published: December 2021

AbstractBackgroundAnopheles stephensi, an invasive malaria vector, has been reported to have three biological forms identifiable mainly based on the number of ridges present on the egg’s floats. Recently, the first intron of the odorant-binding protein-1 (AsteObp1) has been introduced as a molecular marker for the identification of these forms, and based on this marker, the presence of three putative sibling species (designated as species A, B and C) has been proposed. However, there is no data on the association of proposed markers with biological form or putative species on field populations.MethodsField collected and laboratory-reared An. stephensi were characterized for biological forms based on the number of ridges on the egg’ s float. DNA sequencing of the partial AsteObp1 gene of An. stephensi individuals were performed by Sanger’s method, either directly or after cloning with a plasmid vector. Additionally, AsteObp1 sequences of various laboratory lines of An. stephensi were retrieved from a public sequence database.ResultsAsteObp1 intron-1 in Indian An. stephensi populations are highly polymorphic with the presence of more than 13 haplotypes exhibiting nucleotides as well as length-polymorphism (90-to-121 bp). No specific haplotype or a group of closely related haplotypes of intron-1 was found associated with any biological form identified morphologically. High heterozygosity for this marker with a low inbreeding coefficient in field and laboratory populations indicates that this marker is not suitable for the delimitation of putative sibling species, at least in Indian populations.ConclusionsAsteObp1 cannot serve as a marker for identifying biological forms of An. stephensi or putative sibling species in Indian populations.
CRISPR Cas13-based tools to track and manipulate endogenous telomeric repeat-containing RNAs in living cells
Authors: Xu Meng , Chigumira Tafadzwa , Chen Ziheng , Tones Jason , Zhao Rongwei , Dahl Kris Noel , Chenoweth David M. , Zhang Huaiying 
Published: December 2021

AbstractTERRA, TElomeric Repeat-containing RNA, is a long non-coding RNA transcribed from telomeres. Emerging evidence indicates that TERRA regulates telomere maintenance and chromosome end protection in normal and cancerous cells. However, the mechanism of how TERRA contributes to telomere functions is still unclear, partially owing to the shortage of approaches to track and manipulate endogenous TERRA molecules in live cells. Here, we developed a method to visualize TERRA in live cells via a combination of CRISPR Cas13 RNA labeling and Suntag technology. Single-particle tracking reveals that TERRA foci undergo anomalous diffusion in a manner that depends on the timescale and telomeric localization. Furthermore, we used a chemically-induced protein dimerization system to manipulate TERRA subcellular localization in live cells. Overall, our approaches to monitor and control TERRA locations in live cells provide powerful tools to better understand its roles in telomere maintenance and genomic integrity.
Disrupted controlling mechanism of salience network on default-mode network and central-executive network in schizophrenia
Authors: Chand Ganesh B. , Thakuri Deepa S. , Soni Bhavin 
Published: December 2021

AbstractNeuroimaging studies suggest that the human brain consists of intrinsically organized large-scale neural networks. Among those networks, the interplay among default-mode network (DMN), salience network (SN), and central-executive network (CEN)has been widely employed to understand the functional interaction patterns in health and diseases. This triple network model suggests that SN causally controls DMN and CEN in healthy individuals. This interaction is often referred to as the dynamic controlling mechanism of SN. However, such interactions are not well understood in individuals with schizophrenia. In this study, we leveraged resting state functional magnetic resonance imaging (fMRI) data of schizophrenia (n = 67) and healthy controls (n = 81) to evaluate the functional interactions among DMN, SN, and CEN using dynamical causal modeling. In healthy controls, our analyses replicated previous findings that SN regulates DMN and CEN activities (Mann-Whitney U test; p < 10−8). In schizophrenia, however, our analyses revealed the disrupted SN-based controlling mechanism on DMN and CEN (Mann-Whitney U test; p < 10−16). These results indicate that the disrupted controlling mechanism of SN on two other neural networks may be a candidate neuroimaging phenotype in schizophrenia.
Genomic map of blood group alleles in Malaysian indigenous Orang Asli population from whole genome sequences
Authors: Rophina Mercy , Teh Lay Kek , Sivasubbu Sridhar , Scaria Vinod , Salleh Mohd Zaki 
Published: December 2021

AbstractPurposeDifferences in the distribution of RBC antigens defining the blood group types among different populations have been well established. However, very few studies exist that have explored the blood group profiles of indigenous populations worldwide. With the rapid advent of next generation sequencing techniques and availability of population scale genomic datasets, we have successfully explored the blood group profiles of the Orang Aslis, who are the indigenous population of Malaysia and provide a systematic comparison of the same with major global population datasets.MethodsVariant call files from whole genome sequence data (hg19) of 114 Orang Asli were retrieved from The Orang Asli Genome Project (OAGP). Systematic variant annotations were performed using ANNOVAR and only those variants spanning genes of 43 blood group systems and transcription factors KLF1 and GATA1 were filtered. Blood group associated allele and phenotype frequencies were determined and were duly compared with other datasets including Singapore Sequencing Malay Project (SSMP), aboriginal western desert Australians and global population datasets including The 1000 Genomes Project and gnomAD.ResultsThis study reports 4 alleles(rs12075, rs7683365, rs586178 and rs2298720) ofDUFFY, MNS, RH and KIDD blood group systems which were significantly distinct between indigenous Orang Asli and cosmopolitan Malaysians. Eighteen (18) alleles which belong to 14 blood group systems were found distinct in comparison to global population datasets. Although not much significant differences were observed in phenotypes of most blood group systems, major insights were observed on comparing Orang Asli with aboriginal Australians and cosmopolitan Malaysians.ConclusionThis study serves as the first of its kind to utilize genomic data to interpret blood group antigen profiles of the Orang Asli population. In addition, systematic comparison of blood group profiles with related populations were also analysed and documented.
Omicron: A heavily mutated SARS-CoV-2 variant exhibits stronger binding to ACE2 and potently escape approved COVID-19 therapeutic antibodies
Authors: Shah Masaud , Woo Hyun Goo 
Published: December 2021

AbstractThe new SARS-CoV-2 variant of concern “Omicron” was recently (Nov. 24th. 2021) spotted in South Africa and already spread around the world due to its enhanced transmissibility. The variant became conspicuous as it harbors more than thirty mutations in the spike protein with 15 mutations in the RBD region alone, potentially dampening the potency of therapeutic antibodies and enhancing the ACE2 binding. More worrying, Omicron infections have been reported in individuals who have received vaccines jabs in South Africa and Hong Kong. Here, we investigated the binding strength of Omicron with ACE2 and seven monoclonal antibodies that are either approved by FDA for COVID-19 therapy or undergoing phase III clinical trials. Computational mutagenesis and binding free energies could confirm that Omicron Spike binds ACE2 stronger than prototype SARS-CoV-2. Notably, three substitutions, i.e., T478K, Q493K, and Q498R, significantly contribute to the binding energies and doubled electrostatic potential of the RBDOmic-ACE2 complex. Instead of E484K substitution that helped neutralization escape of Beta, Gamma, and Mu variants, Omicron harbors E484A substitution. Together, T478K, Q493K, Q498R, and E484A substitutions contribute to a significant drop in the electrostatic potential energies between RBDOmic-mAbs, particularly in Etesevimab, Bamlanivimab, and CT-p59. CDR diversification could help regain the neutralization strength of these antibodies; however, we could not conduct this analysis to this end. Conclusively, our findings suggest that Omicron binds ACE2 with greater affinity, enhancing its infectivity and transmissibility. Mutations in the Spike are prudently devised by the virus that enhances the receptor binding and weakens the mAbs binding to escape the immune response.
Design principles to assemble drug combinations for effective tuberculosis therapy using interpretable pairwise drug response measurements
Authors: Larkins-Ford Jonah , Degefu Yonatan N. , Van Nhi , Sokolov Artem , Aldridge Bree B. 
Published: December 2021

AbstractA challenge in designing treatment regimens for tuberculosis is the necessity to use three or more antibiotics in combination. The combination space is too large to be comprehensively assayed; therefore, only a small number of possible combinations are tested. We narrowed the prohibitively large search space of combination drug responses by breaking down high-order combinations into units of drug pairs. Using pairwise drug potency and drug interaction metrics from in vitro experiments across multiple growth environments, we trained machine learning models to predict outcomes associated with higher-order combinations in the BALB/c relapsing mouse model, an important preclinical model for drug development. We systematically predicted treatment outcomes of >500 combinations among twelve antibiotics. Our classifiers performed well on test data and predicted many novel combinations to be improved over bedaquiline + pretomanid + linezolid, an effective regimen for multidrug-resistant tuberculosis that also shortens treatment in BALB/c mice compared to the standard of care. To understand the design features of effective drug combinations, we reformulated classifiers as simple rulesets to reveal guiding principles of constructing combination therapies for both preclinical and clinical outcomes. One example ruleset is to include a drug pair that is synergistic in dormancy and another pair that is potent in a cholesterol-rich growth environment. These rulesets are predictive, intuitive, and practical, thus enabling rational construction of effective drug combinations based on in vitro pairwise drug synergies and potencies. As more preclinical and clinical drug combination data become available, we expect to improve predictions and combination design rules.
Junior scientists spotlight social bonds in seminars for diversity, equity, and inclusion in STEM
Authors: Boyle Evan A. , Goldberg Gabriela , Schmok Jonathan C. , Burgado Jillybeth , Layng Fabiana Izidro , Grunwald Hannah A. , Balotin Kylie M. , Cuoco Michael S. , Chang Keng-Chi , Ecklu-Mensah Gertrude , Arakaki Aleena K. S. , Ahmed Noorsher , Arceo Ximena Garcia , Jagannatha Pratibha , Pekar Jonathan , Iyer Mallika ,   DASL Alliance, Yeo Gene W. 
Published: December 2021

AbstractDisparities for women and minorities in science, technology, engineering, and math (STEM) careers have continued even amidst mounting evidence for the superior performance of diverse workforces. In response, we launched the Diversity and Science Lecture series, a cross-institutional platform where junior life scientists present their research and comment on equity, diversity, and inclusion in STEM. We characterize speaker representation from 79 profiles and investigate topic noteworthiness via quantitative content analysis of talk transcripts. Nearly every speaker discussed interpersonal support, and three-fifths of speakers commented on race or ethnicity. Other topics, such as sexual and gender minority identity, were less frequently addressed but highly salient to the speakers who mentioned them. We found that significantly co-occurring topics reflected not only conceptual similarity, such as terms for racial identities, but also intersectional significance, such as identifying as a Latina/Hispanic woman or Asian immigrant, and interactions between priorities and identities, including the heightened value of friendship to the LGBTQ community, which we reproduce using transcripts from an independent seminar series. Our approach to scholar profiles and talk transcripts serves as an example for transmuting hundreds of hours of scholarly discourse into rich datasets that can power computational audits of speaker diversity and illuminate speakers’ personal and professional priorities.
Selective representations of texture and motion in mouse higher visual areas
Authors: Yu Yiyi , Stirman Jeffrey N. , Dorsett Christopher R. , Smith Spencer L. 
Published: December 2021

AbstractMice have a constellation of higher visual areas, but their functional specializations are unclear. Here, we used a data-driven approach to examine neuronal representations of complex visual stimuli across mouse higher visual areas, measured using large field-of-view two-photon calcium imaging. Using specialized stimuli, we found higher fidelity representations of texture in area LM, compared to area AL. Complementarily, we found higher fidelity representations of motion in area AL, compared to area LM. We also observed this segregation of information in response to naturalistic videos. Finally, we explored how popular models of visual cortical neurons could produce the segregated representations of texture and motion we observed. These selective representations could aid in behaviors such as visually guided navigation.
PIPP: Improving peptide identity propagation using neural networks
Authors: Hediyeh-zadeh Soroor , Martin Jarryd , Davis Melissa J. , Webb Andrew I. 
Published: December 2021

AbstractPeptide identity propagation (PIP) can substantially reduce missing values in label-free mass spectrometry quantification by transferring peptides identified by tandem mass (MS/MS) spectra in one run to experimentally related runs where the peptides are not identified by MS/MS. The existing frameworks for matching identifications between runs perform peak tracing and propagation based on similarity of precursor features using only a limited number of dimensions available in MS1 data. These approaches do not produce accompanying confidence estimates and hence cannot filter probable false positive identity transfers. We introduce an embedding based PIP that uses a higher dimensional representation of MS1 measurements that is optimized to capture peptide identities using deep neural networks. We developed a propagation framework that works entirely on MaxQuant results. Current PIP workflows typically perform propagation mainly using two feature dimensions, and rely on deterministic tolerances for identification transfer. Our framework overcomes both these limitations while additionally assigning probabilities to each transferred identity. The proposed embedding approach enables quantification of the empirical false discovery rate (FDR) for peptide identification, while also increasing depth of coverage through coembedding the runs from the experiment with experimental libraries. In published datasets with technical and biological variability, we demonstrate that our method reduces missing values in MaxQuant results, maintains high quantification precision and accuracy, and low false transfer rate.
Effect of everyday discrimination on depression and suicidal ideation during the COVID-19 pandemic: a large-scale, repeated-measures study in theAll of UsResearch Program
Authors: Lee Younga H. , Liu Zhaowen , Fatori Daniel , Bauermeister Joshua R. , Luh Rebecca A. , Clark Cheryl R. , Bauermeister Sarah , Brunoni André R. , Smoller Jordan W. 
Published: December 2021

AbstractObjectiveThe COVID-19 pandemic has coincided with an increase in depressive symptoms as well as a growing awareness of health inequities and structural racism in the United States. Here, we examine the mental health impact of everyday discrimination during the pandemic in a large and diverse cohort of theAll of UsResearch Program.MethodsUsing repeated assessments of 62,651 participants in May to July of 2020, we fitted mixed-effects models to assess the effect of everyday discrimination on moderate to severe depression (Patient Health Questionnaire (PHQ)-9 ≥ 10) and suicidal ideation (PHQ-9 item 9 > 0), and applied inverse probability weights to account for non-random probabilities of completing the voluntary survey.ResultsEveryday discrimination was associated with increased odds of depression (adjusted odds ratio (aOR) [95% CI]: 1.21 [1.20 -1.22]) and suicidal ideation (1.17 [1.16-1.18]). For depression, the effects were larger in earlier phases of the pandemic (interaction p=8.2×10−5), which varied by main reason for discrimination and self-reported race and ethnicity. Among those who identified race or ancestry/national origin(s) as a primary reason for discrimination, Asian and Black or African American participants had 24% and 17% increase in the odds of depression in May of 2020 (1.24 [1.17-1.31] and 1.17 [1.12-1.22]), respectively, versus a 3% and 7% increase in July (1.03 [0.96-1.10] and 1.07 [1.02-1.12]).ConclusionIn this large and diverse sample, increased levels of everyday discrimination were associated with higher odds of depression, particularly during the early phase of the pandemic among participants self-identifying as Asian or Black.
Kidney failure alters parathyroid Pin1 phosphorylation and parathyroid hormone mRNA binding proteins leading to secondary hyperparathyroidism
Authors: Hasan Alia , Pollak Yael E. , Kilav-Levin Rachel , Silver Justin , London Nir , Nechama Morris , Ben-Dov Iddo Z. , Naveh-Many Tally 
Published: December 2021

AbstractParathyroid hormone (PTH) regulates calcium metabolism and bone strength. Chronic kidney disease leads to secondary hyperparathyroidism (SHP) which increases morbidity and mortality. In experimental SHP, the increasedPTHgene expression is due to enhancedPTHmRNA stability, mediated by changes in its interaction with stabilizing AUF1 and destabilizing KSRP. Pin1 isomerizes target proteins and leads to KSRP dephosphorylation. In SHP, Pin1 isomerase activity is decreased and phosphorylated KSRP fails to bindPTHmRNA, resulting in highPTHmRNA stability and levels. However, the up- and down-stream mechanisms by which kidney failure stimulates the parathyroid remain elusive. We now reveal a pathway where kidney failure induces parathyroid Pin1 phosphorylation, linking Pin1, KSRP and PTH mRNA stability as key players for the high PTH expression in SHP. We identified by mass-spectrometry, changes in rat parathyroid proteome and phosphoproteome profiles induced by impaired renal function, including KSRP phosphorylation at Pin1 target sites. Furthermore, both acute and chronic kidney failure led to parathyroid-specific Pin1 Ser16 and Ser71 phosphorylation, which disrupts Pin1 activity. Accordingly, pharmacologic Pin1 inhibition, that mimics the decreased Pin1 activity in SHP, increased PTH expression ex-vivo in parathyroid organ cultures and in transfected cells, through thePTHmRNA protein-interacting element and KSRP phosphorylation at potential Pin1-binding motifs. Therefore, kidney failure leads to loss of parathyroid Pin1 activity by inducing Pin1 phosphorylation. This predisposes parathyroids to increase PTH production through impairedPTHmRNA decay that is dependent on KSRP phosphorylation. Pin1 and KSRP phosphorylation and the Pin1-KSRP-PTHmRNA axis thus drive SHP.
N-acetyl-cysteinylated streptophenazines from Streptomyces
Authors: Vind Kristiina , Maffioli Sonia , Ciruelos Blanca Fernandez , Waschulin Valentin , Brunati Cristina , Simone Matteo , Sosio Margherita , Donadio Stefano 
Published: December 2021

ABSTRACTHere, we describe two N-acetyl-cysteinylated streptophenazines (1 and 2) produced by soil-derived Streptomyces sp. ID63040 and identified through a metabolomic approach. These metabolites attracted our interest due to their low occurrence frequency in a large library of fermentation broth extracts and their consistent presence in biological replicates of the producer strain. The compounds were found to possess broad-spectrum antibacterial activity while exhibiting low cytotoxicity. The biosynthetic gene cluster from Streptomyces sp. ID63040 was found to be highly similar to the streptophenazine reference cluster in the MIBiG database, which originates from the marine Streptomyces sp. CNB-091. Compounds 1 and 2 were the main streptophenazine products from Streptomyces sp. ID63040 at all cultivation times, but were not detected in Streptomyces sp. CNB-091. The lack of obvious candidates for cysteinylation in the Streptomyces sp. ID63040 biosynthetic gene cluster suggests that the N-acetyl-cysteine moiety derives from cellular functions, most likely from mycothiol. Overall, our data represent an interesting example on how to leverage metabolomics for the discovery of new natural products and point out to the often-neglected contribution of house-keeping cellular functions to natural product diversification.Graphical abstract
A two-step metagenomics approach for prey identification from the blood meals of common vampire bats (Desmodus rotundus)
Authors: Shi Chua Physilia Ying , Carøe Christian , Crampton-Platt Alex , Reyes-Avila Claudia Sarai , Jones Gareth , Streicker Daniel G. , Bohmann Kristine 
Published: December 2021

ABSTRACTThe feeding behaviour of the sanguivorous common vampire bat (Desmodus rotundus) facilitates the transmission of pathogens that can impact both human and animal health. To formulate effective strategies in controlling the spread of diseases, there is a need to obtain information on which animals they feed on. One DNA-based approach, shotgun sequencing, can be used to obtain such information. Even though it is costly, shotgun sequencing can be used to simultaneously retrieve prey and vampire bat mitochondrial DNA for population studies within one round of sequencing. However, due to the challenges of analysing shotgun sequenced metagenomic data such as false negatives/positives and typically low proportion of reads mapped to diet items, shotgun sequencing has not been used for the identification of prey from common vampire bat blood meals. To overcome these challenges and generate longer mitochondrial contigs which could be useful for prey population studies, we shotgun sequenced common vampire bat blood meal samples (n=8) and utilised a two-step metagenomic approach based on combining existing bioinformatic workflows (alignment and de novo mtDNA assembly) to identify prey. Further, we validated our results to detections made through metabarcoding. We accurately identified the common vampire bats’ prey in seven out of eight samples without any false positives. We also generated prey mitochondrial contig lengths between 138bp to 3231bp (mean=985bp, SD=981bp). As we develop more computationally efficient bioinformatics pipelines and reduce sequencing costs, we can expect an uptake in metagenomics dietary studies in the near future.