bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benchmarking observational analyses before using them to address questions trials cannot answer: an application to coronary thrombus aspiration
Authors: Matthews Anthony A. , Dahabreh Issa J. , Fröbert Ole , Lindahl Bertil , James Stefan , Feychting Maria , Jernberg Tomas , Berglund Anita , Hernán Miguel A. 
Published: September 2021

AbstractTo increase confidence in the use of observational analyses when addressing effectiveness questions beyond those addressed by randomized trials, one can first benchmark the observational analyses against existing trial results. We use Swedish registry data to emulate a target trial similar to the TASTE randomized trial, which found no difference in the risk of death or myocardial infarction by 1 year with or without thrombus aspiration among individuals with ST-elevation myocardial infarction. We benchmark the emulation against the trial at 1 year, then extend the emulation’s follow up to 3 years and estimate effects in subpopulations underrepresented in the trial. As in the TASTE trial, the observational analysis found no differences in risk of outcomes by 1 year between groups (risk difference 0.7 (−0.7,2.0) and -0.2 (−1.3,1.0) for death and myocardial infarction respectively), so benchmarking was considered successful. We additionally show no difference in risk of death or myocardial infarction by 3 years, or within subpopulations by 1 year. Benchmarking against an index trial before using observational analyses to answer questions beyond those the trial could address allowed us to explore whether the observational data can be trusted to deliver valid estimates of treatment effects.
Symbiotic bacterial community ofDrosophila melanogasterchanges with nutritional modifications of the diet but can alleviate negative effects on larval phenotypes
Authors: Bombin Andrei , Cunneely Owen , Bombin Sergei , Eickman Kira , Ruesy Abigail , Cowan Rachael , Myers Abigail , Su Mengting , Mosley Jonathan , Ferguson Jane , Reed Laura 
Published: September 2021

ABSTRACTObesity is an increasing pandemic and is caused by multiple factors including genotype, psychological stress, and gut microbiota. Our project investigated the effects produced by high fat and high sugar dietary modifications on microbiota and metabolic phenotype ofDrosophila melanogaster. Larvae raised on the high fat and high sugar diets exhibited bacterial communities that were compositionally and phylogenetically different from bacterial communities of the larvae raised on normal diets, especially if parental microbiota were removed. Several of the dominant bacteria taxa that are commonly associated with high fat and high sugar diets across model organisms and even human populations showed similar pattern in our results.CorynebacteriaceaeandErysipelotrichaceaewere connected with high fat food, whileEnterobacteriaceaeandLactobacillaceaewere associated with high sugar diets. In addition, we observed that presence of symbiotic microbiota often mitigated the effect that harmful dietary modifications produced on larvae, including elevated triglyceride concentrations and was crucial forDrosophilasurvival, especially on high sugar peach diets.
Naturalistic hyperscanning with wearable magnetoencephalography
Authors: Holmes Niall , Rea Molly , Hill Ryan M. , Boto Elena , Stuart Andrew , Leggett James , Edwards Lucy J. , Rhodes Natalie , Shah Vishal , Osborne James , Fromhold T. Mark , Glover Paul , Montague P. Read , Brookes Matthew J. , Bowtell Richard 
Published: September 2021

AbstractThe evolution of human cognitive function is reliant on complex social interactions which form the behavioural foundation of who we are. These social capacities are subject to dramatic change in disease and injury; yet their supporting neural substrates remain poorly understood. Hyperscanning employs functional neuroimaging to simultaneously assess brain activity in two individuals and offers the best means to understand the neural basis of social interaction. However, present technologies are limited, either by poor performance (low spatial/temporal precision) or unnatural scanning environment (claustrophobic scanners, with interactions via video). Here, we solve this problem by developing a new form of hyperscanning using wearable magnetoencephalography (MEG). This approach exploits quantum sensors for MEG signal detection, in combination with high-fidelity magnetic field control – afforded by a novel “matrix coil” system – to enable simultaneous scanning of two freely moving participants. We demonstrate our approach in a somatosensory task and an interactive ball game. Despite large and unpredictable subject motion, sensorimotor brain activity was delineated clearly in space and time, and correlation of the envelope of neuronal oscillations between people was demonstrated. In sum, unlike existing modalities, wearable-MEG combines high fidelity data acquisition and a naturalistic setting, which will facilitate a new generation of hyperscanning.
GABOLA: A Reliable Gap-Filling Strategy for de novo Chromosome-Level Assembly
Authors: Chuang Wei-Hsuan , Cheng Hsueh-Chien , Chang Yu-Jung , Fu Pao-Yin , Huang Yi-Chen , Hsieha Ping-Heng , Chen Shu-Hwa , Lina Chung-Yen , Ho Jan-Ming 
Published: September 2021

AbstractWe propose a novel method, GABOLA, which utilizes long-range genomic information provided by accurate linked short reads jointly with long reads to improve the integrity and resolution of whole genome assemblies especially in complex genetic regions. We validated GABOLA on human and Japanese eel genomes. On the two human samples, we filled in more bases spanning 23.3Mbp and 46.2Mbp than Supernova assembler, covering over 3,200 functional genes which includes 8,500 exons and 15,000 transcripts. Among them, multiple genes related to various types of cancer were identified. Moreover, we discovered additional 11,031,487 base pairs of repeat sequences and 218 exclusive repeat patterns, some of which are known to be linked to several disorders such as neuron degenerative diseases. As for the eel genome, we successfully raised the genetic benchmarking score to 94.6% while adding 24.7 million base pairs. These results manifest the capability of GABOLA in the optimization of whole genome assembly and the potential in precise disease diagnosis and high-quality non-model organism breeding.Availability: The docker image and source code of GABOLA assembler are available at https://hub.docker.com/r/lsbnb/gabola and https://github.com/lsbnb/gabola respectively.
Diet specialization in an insular population of coastal Peregrine Falcons
Authors: Sutton Luke J. , Loram Sebastian W. 
Published: September 2021

AbstractIndividual diet specialization is known to occur in populations of generalist predators, where specific individuals develop specialist feeding strategies. Diet specialization has been reported in many raptor species, and it may be an important driver of intraspecific population structure. Here, we quantify the diet of five breeding pairs of Peregrine FalconsFalco peregrinusfrom an offshore island determined from prey remains collected over four breeding seasons. Three prey species accounted for 69.8 % of total prey frequency, with Manx ShearwaterPuffinus puffinusthe primary prey accounting for 47.3 % by frequency and 40.8 % by biomass. Herring GullLarus argentatuswas the second most important prey species by frequency (13.8 %) and biomass (29.8 %) followed by Domestic PigeonColumba livia(frequency = 8.7 %, biomass = 7.0 %). Predation frequency on specific prey groups varied substantially between breeding pairs and months. Two pairs specialized on Manx Shearwater, one pair specialized on Herring Gull and Manx Shearwater, with the remaining two pairs having a relatively generalist diet of Manx Shearwaters, Domestic Pigeon and small passerines. Predation on Manx Shearwaters increased throughout the breeding season with a peak in total diet frequency of 63.8 % in July, with a concurrent decrease in Herring Gull predation frequency. Higher percentage of Manx Shearwater in the diet was able to explain 87 % of the variation in a narrower dietary breadth for the Peregrine pairs. Our results suggest individual diet specialization may be important for understanding population density in insular raptor populations.
Roles of cellular senescence in driving bone marrow adiposity in radiation- and aging-associated bone loss
Authors: Chandra Abhishek , Lagnado Anthony B. , Farr Joshua N. , Schleusner Megan , Monroe David G. , Hachfeld Christine , Passos João F. , Khosla Sundeep , Pignolo Robert J. 
Published: September 2021

AbstractOsteoporosis is associated with an increase in marrow adipocytes, collectively termed bone marrow adipose tissue (BMAT). An increase in BMAT is linked with decline of mesenchymal progenitors that give rise to osteoblasts which are responsible for bone accrual. Oxidative stress-induced reactive oxygen species, DNA damage, apoptosis and cellular senescence have been associated with reduced osteoprogenitors in a reciprocal fashion to BMAT; however, a direct (causal) link between cellular senescence and BMAT is still elusive. Accumulation of senescent cells occur in naturally aged and in focally radiated bone tissue, but despite amelioration of age- and radiation-associated bone loss after senescent cell clearance, molecular events that precede BMAT accrual are largely unknown. Using a mouse model here we show by RNA-Sequencing data that BMAT-related genes were the most upregulated gene subset in radiated bones. Using focal radiation as a model to understand age-associated changes in bone, we performed a longitudinal assessment of cellular senescence and BMAT. Using qRT-PCR, RNA in situ hybridization and histological assessment of telomere dysfunction as a marker of senescence, we observed increased p21 transcripts in bone lining cells, osteocytes and bone marrow cells, and elevated dysfunctional telomeres in osteocytes starting from day 1 post-radiation, without the presence of BMAT. BMAT was significantly elevated in radiated bones at day 7, confirming the qRT-PCR data in which most BMAT-related genes were elevated by day 7, and the trend continued until day 42 post-radiation. Similarly, elevation in BMAT-related genes was observed in aged bones. The senolytic cocktail of Dasatinib (D) plus Quercetin (Q) – D+Q, which clears senescent cells, reduced BMAT in aged and radiated bones. MicroRNAs (miRs) linked with senescence marker p21 were downregulated in radiated- and aged-bones, while miR-27a, a miR that is associated with increased BMAT, was elevated both in radiated- and aged-bones. D+Q downregulated miR-27a in radiated bones at 42 days post-radiation. Overall, our study provides evidence that BMAT occurrence in oxidatively stressed bone environments, such as radiation and aging, is induced following a common pathway and is dependent on the presence of senescent cells.
Clustering single cell CITE-seq data with a canonical correlation based deep learning method
Authors: Yuan Musu , Chen Liang , Deng Minghua 
Published: September 2021

AbstractSingle cell sequencing examines the sequence information from individual cells with optimized next generation sequencing (NGS) technologies. It provides researchers a higher resolution of cellular differences and a better understanding of the function of an individual cell in the context of its microenvironment. CITE-seq, or Cellular Indexing of Transcriptomes and Epitopes by sequencing, is one of the latest innovations in the domain of single cell sequencing. It enables researchers to simultaneously capture RNA and surface protein expression on the same cells so that we can correlate the two data types, identify biomarkers and better characterize cell phenotypes. Although multi-omics sequencing technologies developed rapidly, data analyzing methods tailored for multiomics sequencing data are lacking. Several serious problems have to be faced. An important one is how to integrate the information from different modalities, namely scRNA and protein data, efficiently.In this paper, we introduce a canonical correlation based deep learning method called scCTClust for clustering analysis over CITE-seq data. We impute and extract the characteristics of the high dimensional RNA part of data with a ZINB model-based autoencoder. A t-kernel distance is introduced to measure the similarity between query cell and cluster centroids. And the protein data rectifies the feature extraction of scRNA data in a canonical correlation analysis(CCA) way. Extensive data experiments shows that scCTClust can precisely recover the dropout values for RNA sequencing data and extract authentic information from both modalities, getting a much better clustering result than state-of-the-art methods, no matter single-omic or multi-omics clustering algorithms.
Common and distinct neurofunctional representations of core and social disgust in the brain: Coordinate-based and network meta-analyses
Authors: Gan Xianyang , Zhou Xinqi , Li Jialin , Jiao Guojuan , Jiang Xi , Biswal Bharat , Yao Shuxia , Klugah-Brown Benjamin , Becker Benjamin 
Published: September 2021

ABSTRACTDisgust represents a multifaceted defensive-avoidance response. On the behavioral level, the response includes withdrawal and a disgust-specific facial expression. While both serve the avoidance of pathogens, the latter additionally transmits social-communicative information. Given that common and distinct brain representation of the primary defensive-avoidance response (core disgust) and encoding of the social-communicative signal (social disgust) remain debated, we employed neuroimaging meta-analyses to (1) determine brain systems generally engaged in disgust processing, and (2) segregate common and distinct brain systems for core and social disgust. Disgust processing, in general, engaged a bilateral network encompassing the insula, amygdala, occipital and prefrontal regions. Core disgust evoked stronger reactivity in left-lateralized threat detection and defensive response network including amygdala, occipital and frontal regions while social disgust engaged a right-lateralized superior temporal-frontal network engaged in social cognition. Anterior insula, inferior frontal and fusiform regions were commonly engaged during core and social disgust, suggesting a common neural basis. We demonstrate a common and separable neural basis of primary disgust responses and encoding of associated social-communicative signals.
Different encoding of reward location in dorsal and ventral hippocampus
Authors: Jarzebowski Przemyslaw , Hay Y. Audrey , Grewe Benjamin F. , Paulsen Ole 
Published: September 2021

SummaryHippocampal neurons encode a cognitive map for spatial navigation1. When they fire at specific locations in the environment, they are known as place cells2. In the dorsal hippocampus place cells accumulate at current navigational goals, such as learned reward locations3–6. In the intermediate-to-ventral hippocampus (here collectively referred to as ventral hippocampus), neurons fire across larger place fields7–10 and regulate reward- seeking behavior11–16, but little is known about their involvement in reward-directed navigation. Here, we compared the encoding of learned reward locations in the dorsal and ventral hippocampus during spatial navigation. We used calcium imaging with a head- mounted microscope to track the activity of CA1 cells over multiple days during which mice learned different reward locations. In dorsal CA1 (dCA1), the overall number of active place cells increased in anticipation of reward but the recruited cells changed with the reward location. In ventral CA1 (vCA1), the activity of the same cells anticipated the reward locations. Our results support a model in which the dCA1 cognitive map incorporates a changing population of cells to encode reward proximity through increased population activity, while the vCA1 provides a reward-predictive code in the activity of a specific subpopulation of cells. Both of these location-invariant codes persisted over time, and together they provide a dual hippocampal reward-location code, assisting goal- directed navigation17, 18.
SUMOylation of Dorsal attenuates Toll/NF-κB signalling
Authors: Hegde Sushmitha , Sreejan Ashley , Gadgil Chetan J , Ratnaparkhi Girish S 
Published: September 2021

AbstractIn Drosophila, Toll/NF-κB signalling plays key roles in both animal development and in host defence. The activation, intensity and kinetics of Toll signalling is regulated by post-translational modifications such as phosphorylation, SUMOylation or ubiquitination that target multiple proteins in the Toll/NF-κB cascade.Here, we have generated a CRISPR-Cas9 edited Dorsal (DL) variant that is SUMO conjugation resistant (SCR). Intriguingly, embryos laid by dlSCR mothers overcome dl haploinsufficiency and complete the developmental program. This ability appears to be a result of higher transcriptional activation by DLSCR. In contrast, SUMOylation dampens DL transcriptional activation, ultimately conferring robustness to the dorso-ventral program. In the larval immune response, dlSCR animals show increase in crystal cell numbers, stronger activation of humoral defence genes, high cactus levels and cytoplasmic stabilization of DL:Cactus complexes. A mathematical model that evaluates the contribution of the small fraction of SUMOylated DL (<5%) suggests that it acts to block transcriptional activation, driven primarily by DL that is not SUMO conjugated.Our findings define SUMO conjugation as an important regulator of the Toll signalling cascade, in both development and in host defense. Our results broadly indicate that SUMO attenuates DL at the level of transcriptional activation. Further, we hypothesize that SUMO conjugation of DL may be part of a Ubc9 dependant feedback circuit that restrains Toll/NF-κB signalling.
The temporal dynamics of the sea urchin regulome
Authors: Feuda Roberto 
Published: September 2021

AbstractIn this work, we used Nanostring N-counter technology, to evaluate the mRNA expression level of more than 330 regulatory genes over 34-time points covering the first three days of development of the sea urchin larvae. The hierarchical clustering of the mRNAs expression levels has identified groups corresponding to the major developmental landmarks (e.g., maternal to zygotic transition and gastrulation). Furthermore, comparison with previous experiments indicates high reproducibility of mRNA level temporal dynamics across batches. Finally, we generated an online tool to visualize gene expression during sea urchin larval development. The site can be accessed at https://nanostring2021.herokuapp.com/.
Comparative metabolomics with Metaboseek reveals functions of a conserved fat metabolism pathway inC. elegans
Authors: Helf Maximilian J. , Fox Bennett W. , Artyukhin Alexander B. , Zhang Ying K. , Schroeder Frank C. 
Published: September 2021

ABSTRACTUntargeted metabolomics via high-resolution mass spectrometry (HRMS) can reveal more than 100,000 molecular features in a single sample, many of which may represent unidentified metabolites, posing significant challenges to data analysis. We here introduce Metaboseek, an open-source analysis platform designed for untargeted comparative metabolomics and demonstrate its utility by uncovering biosynthetic functions of a conserved fat metabolism pathway, α-oxidation, usingC. elegansas a model. Metaboseek integrates modules for molecular feature detection, statistics, molecular formula prediction, and fragmentation (MS/MS) analysis, which uncovered more than 200 previously uncharacterized α-oxidation-dependent metabolites in an untargeted comparison of wildtype and α-oxidation-defectivehacl-1mutants. The identified metabolites support the predicted enzymatic function of HACL-1 and revealed that α-oxidation participates in metabolism of endogenous β-methyl-branched fatty acids and food-derived cyclopropane lipids. Our results showcase compound discovery and feature annotation at scale via untargeted comparative metabolomics applied to a conserved primary metabolic pathway and suggest a model for the metabolism of cyclopropane lipids.
Multiscale Simulation of an Influenza A M2 Channel Mutant Reveals Key Features of Its Markedly Different Proton Transport Behavior
Authors: Watkins Laura C. , DeGrado William F. , Voth Gregory A. 
Published: September 2021

ABSTRACTThe influenza A M2 channel, a prototype for the viroporin class of viral channels, is an acid-activated viroporin that conducts protons across the viral membrane, a critical step in the viral life cycle. As the protons enter from the viral exterior, four central His37 residues control the channel activation by binding subsequent protons, which opens the Trp41 gate and allows proton flux to the viral interior. Asp44 is essential for maintaining the Trp41 gate in a closed state at high pH, which results in asymmetric conduction. The prevalent D44N mutant disrupts this gate and opens the C-terminal end of the channel, resulting in overall increased conduction in the physiologically relevant pH range and a loss of this asymmetric conduction. Here, we use extensive Multiscale Reactive Molecular Dynamics (MS-RMD) and Quantum Mechanics/Molecular mechanics (QM/MM) simulations with an explicit, reactive excess proton to calculate the free energy of proton transport in the M2 mutant and to study the dynamic molecular-level behavior of D44N M2. We find that this mutation significantly lowers the barrier of His37 deprotonation in the activated state and shifts the barrier for entry up to the Val27 tetrad. These free energy changes are reflected in structural shifts. Additionally, we show that the increased hydration around the His37 tetrad diminishes the effect of the His37 charge on the channel’s water structure, facilitating proton transport and enabling activation from the viral interior. Altogether, this work provides key insight into the fundamental characteristics of PT in WT M2 and how the D44N mutation alters this PT mechanism, and it expands our understanding of the role of emergent mutations in viroporins.
Human generation times across the past 250,000 years
Authors: Wang Richard J. , Al-Saffar Samer I. , Rogers Jeffrey , Hahn Matthew W. 
Published: September 2021

AbstractThe generation times of our recent ancestors can tell us about both the biology and social organization of prehistoric humans, placing human evolution on an absolute timescale. We present a method for predicting historic male and female generation times based on changes in the mutation spectrum. Our analyses of whole-genome data reveal an average generation time of 26.9 years across the past 250,000 years, with fathers consistently older (30.7 years) than mothers (23.2 years). Shifts in sex-averaged generation times have been driven primarily by changes to the age of paternity rather than maternity, though we report a disproportionate increase in female generation times over the past several thousand years. We also find a large difference in generation times among populations, with samples from current African populations showing longer ancestral generation times than non-Africans for over a hundred thousand years, reaching back to a time when all humans occupied Africa.