bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloud-native distributed genomic pileup operations
Authors: Wiewiórka Marek , Szmurło Agnieszka , Stankiewicz Paweł , Gambin Tomasz 
Published: August 2022

AbstractMotivationPileup analysis is a building block of many bioinformatics pipelines, including variant calling and genotyping. This step tends to become a bottleneck of the entire assay since the straightforward pileup implementations involve processing of all base calls from all alignments sequentially. On the other hand, a distributed version of the algorithm faces the intrinsic challenge of splitting reads-oriented file formats into self-contained partitions to avoid costly data exchange between computation nodes.ResultsHere, we present a scalable, distributed, and efficient implementation of a pileup algorithm that is suitable for deploying in cloud computing environments. In particular, we implemented: (i) our custom data-partitioning algorithm optimized to work with the alignment reads, (ii) a novel and unique approach to process alignment events from sequencing reads using the MD tags, (iii) the source code micro-optimizations for recurrent operations, and (iv) a modular structure of the algorithm. We have proven that our novel approach consistently and significantly outperforms other state-of-the-art distributed tools in terms of execution time (up to 6.5x faster) and memory usage (up to 2x less), resulting in a substantial cloud cost reduction. SeQuiLa is a cloud-native solution that can be easily deployed using any managed Kubernetes and Hadoop services available in public clouds, like Microsoft Azure Cloud, Google Cloud Platform, or Amazon Web Services. Together with the already implemented distributed range joins and coverage calculations, our package provides end-users with an unified SQL interface for convenient analyzing of population-scale genomic data in an interactive way.Availabilityhttps://biodatageeks.github.io/sequila/Contacttomasz.gambin@pw.edu.plSupplementary informationSupplementary data are available at Bioinformatics online.
Kinetics-based Inference of Environment-Dependent Microbial Interactions and Their Dynamic Variation
Authors: Song Hyun-Seob , Lee Na-Rae , Kessell Aimee K. , McCullough Hugh C. , Park Seo-Young , Zhou Kang , Lee Dong-Yup 
Published: August 2022

ABSTRACTMicrobial communities in nature are dynamically evolving as member species change their interactions subject to environmental variations. Accounting for such context-dependent dynamic variations in interspecies interactions is critical for predictive ecological modeling. In the absence of generalizable theoretical foundations, we lack a fundamental understanding of how microbial interactions are driven by environmental factors, significantly limiting our capability to predict and engineer community dynamics and function. To address this issue, we propose a novel theoretical framework that allows us to represent interspecies interactions as an explicit function of environmental variables (such as substrate concentrations) by combining growth kinetics and a generalized Lotka-Volterra model. A synergistic integration of these two complementary models leads to the prediction of alterations in interspecies interactions as the outcome of dynamic balances between positive and negative influences of microbial species in mixed relationships. This unique capability of our approach was experimentally demonstrated using a synthetic consortium of twoEscherichia colimutants that are metabolically dependent (due to an inability to synthesize essential amino acids), but competitively growing on a shared substrate. The analysis of theE. colibinary consortium using our model not only showed how interactions between the two amino acid auxotrophic mutants are controlled by the dynamic shifts in limiting substrates, but also enabled quantifying previously uncharacterizable complex aspects of microbial interactions such as asymmetry in interactions. Our approach can be extended to other ecological systems to model their environment-dependent interspecies interactions from growth kinetics.IMPORTANCEModeling of environment-controlled interspecies interactions through separate identification of positive and negative influences of microbes in mixed relationships is a new capability that can significantly improve our ability to understand, predict, and engineer complex dynamics of microbial communities. Moreover, robust prediction of microbial interactions as a function of environmental variables can serve as valuable benchmark data to validate modeling and network inference tools in microbial ecology, the development of which has often been impeded due to the lack of ground truth information on interactions. While demonstrated against microbial data, the theory developed in this work is readily applicable to general community ecology to predict interactions among microorganisms such as plants and animals, as well as microorganisms.
Prioritizing landscapes to reconcile biodiversity conservation, ecosystem services, and human well-being in India
Authors: Srivathsa Arjun , Vasudev Divya , Nair Tanaya , Chakrabarti Stotra , Chanchani Pranav , DeFries Ruth , Deomurari Arpit , Dutta Sutirtha , Ghose Dipankar , Goswami Varun R. , Nayak Rajat , Neelakantan Amrita , Thatte Prachi , Vaidyanathan Srinivas , Verma Madhu , Krishnaswamy Jagdish , Sankaran Mahesh , Ramakrishnan Uma 
Published: August 2022

AbstractBiodiversity conservation and human well-being are tightly interlinked; yet mismatches in the scale at which both priorities are planned and implemented have exacerbated biodiversity loss, erosion of ecosystem services, and declining human quality of life. India houses the second largest human population on the planet, while <5% of the country’s land area is effectively protected for conservation. This warrants landscape-level conservation planning through a judicious mix ofland-sharingandland-sparingapproaches, and co-production of ecosystem services. Through a multi-faceted assessment, we prioritize spatial extents of land parcels that, in the face of anthropogenic threats, can safeguard conservation landscapes across India’s biogeographic zones. We find that only a fraction (~15%) of such priority areas identified here are encompassed under India’s extant PA network, and several landscapes of high importance were omitted in all previous global-scale assessments. We then examined the spatial congruence of priority areas with administrative units earmarked for economic development by the Indian government, and propose management-zoning through state-driven and participatory approaches. Our spatially explicit insights can help meet the twin goals of biodiversity conservation and sustainable development in India and other countries across the Global South.
Aging Differentially Affects Axonal Autophagosome Formation and Maturation
Authors: Tsong Heather , Holzbaur Erika , Stavoe Andrea KH 
Published: August 2022

ABSTRACTMisregulation of neuronal autophagy has been implicated in age-related neurodegenerative diseases including Parkinson’s disease and Huntington’s disease. We compared autophagosome formation and maturation in primary murine neurons during development and through aging to elucidate how aging affects neuronal autophagy. We observed an age-related decrease in the rate of formation of LC3B-positive autophagosomes leading to a significant decrease in the density of autophagosomes along the axon. Next, we assessed the maturation of autophagic vesicles and identified a surprising increase in their maturation in neurons from aged mice. While we did not detect notable changes in endolysosomal content in the distal axon during aging, we found that autophagic vesicles were transported more efficiently in neurons from adult mice than in neurons from young mice. This efficient transport of autophagic vesicles in both the distal and proximal axon is maintained in neurons from aged mice and indicates that aging alone does not impair transport nor negatively impact the later stages of autophagy. However, the pronounced deficit in autophagosome biogenesis in aged neurons may contribute to a decreased capacity to clear aggregated proteins or dysfunctional organelles and thus contribute to age-related degeneration.
Co-obligate symbioses have repeatedly evolved across aphids, but partner identity and nutritional contributions vary across lineages
Authors: Manzano-Marín Alejandro , d’acier Armelle Coeur , Clamens Anne-Laure , Cruaud Corinne , Barbe Valérie , Jousselin Emmanuelle 
Published: August 2022

ABSTRACTAphids are a large family of phloem-sap feeders. They typically rely on a single bacterial endosymbiont,Buchnera aphidicola, to supply them with essential nutrients lacking in their diet. This association withBuchnerawas described in model aphid species from the Aphidinae subfamily and has been assumed to be representative of most aphids. However, in two lineages,Buchnerahas lost some essential symbiotic functions and is now complemented by additional symbionts. Though these cases break our view of aphids harbouring a single obligate endosymbiont, we know little about the extent, nature, and evolution of these associations across aphid subfamilies. Here, using metagenomics on 25 aphid species from nine subfamilies, re-assembly and re-annotation of 20 aphid symbionts previously sequenced, and 16S rRNA amplicon sequencing on 223 aphid samples (147 species from 12 subfamilies), we show that dual symbioses have evolved anew at least six times. We also show that these secondary co-obligate symbionts have typically evolved from facultative symbiotic taxa. Genome-based metabolic inference confirms interdependencies betweenBuchneraand its partners for the production of essential nutrients but shows contributions vary across pairs of co-obligate associates. Fluorescentin situhybridisation microscopy shows a common bacteriocyte localisation of two newly acquired symbionts. Lastly, patterns ofBuchneragenome evolution reveal that small losses affecting a few key genes can be the onset of these dual systems, while large gene losses can occur without any co-obligate symbiont acquisition. Hence, theBuchnera-aphid association, often thought of as exclusive, seems more flexible, with a few metabolic losses having recurrently promoted the establishment of a new co-obligate symbiotic partner.
The zebrafish dmrt family genes have cooperative and antagonistic roles in sex determination and oogenesis
Authors: Steinfeld Jocelyn S. , Ameyaw Keith K. , Wood Christopher G. , Johnston Ryan M. , Escauriza Ana J. Johnson , Torija Emma G. , Quiles Kiloni , Venkataramani Kavita , MacNeil Jessica N. , Siegfried Kellee R. 
Published: August 2022

ABSTRACTThe double-sex and mab3 related transcription factor (dmrt) gene family has conserved roles in sex determination and gonad development across metazoans. In zebrafish, dmrt1 was previously shown to function in male sex-determination and testes development. To gain a broader knowledge of this gene family in sexual development, we investigated potential roles of all zebrafish dmrt family genes in sex-determination and gonad development using mutant analysis. The dmrt2a and dmrt5 mutants conferred lethality prior to sex differentiation, whereas dmrt2b and dmrt3 mutants were viable and fertile. Dmrt2b mutants had normal sex ratios while dmrt3 showed slightly skewed sex ratios in some experiments, indicating that dmrt3 has a minor role in sex-determination. We report a previously unknown role for dmrt1 in ovary development. Although dmrt1 mutant females were fertile, oogenesis did not progress normally, as evident from abnormal proportions of differently-staged oocytes within mutant ovaries. We also asked if dmrt1 mutant phenotypes could be modified by loss of another dmrt family member. Analysis of dmrt1;dmrt2a mutants was possible as these double mutants were sub-viable, showing a partial rescue of the dmrt2a lethality in the dmrt1 mutant background. The dmrt1;dmrt2a mutants had less severe female bias than dmrt1 mutants suggesting that dmrt2a acts antagonistically to dmrt1 in sex determination. Double mutants of dmrt1 with either dmrt2a or dmrt3 had more severe oogenesis defects than dmrt1 mutants and had either sub-fertility with reduced fecundity or failed to breed, respectively. This study reveals previously unknown roles of zebrafish dmrt1, dmrt2a, and dmrt3 in oogenesis.
Evidence for the Existence of a Bacterial Etiology for Alzheimer’s Disease and for a Temporal-Spatial Development of a Pathogenic Microbiome in the Brain
Authors: Moné Yves , Earl Joshua P. , Król Jarosław E. , Ahmed Azad , Sen Bhaswati , Ehrlich Garth D. , Lapides Jeffrey R. 
Published: August 2022

ABSTRACTBackgroundOver the last few decades, a growing body of evidence suggests a role for various infectious agents in Alzheimer’s Disease (AD) pathogenesis. Despite diverse pathogens (virus, bacteria, or fungi) being detected in AD subjects’ brains, most research has focused on individual pathogens and only a few studies investigated the hypothesis of a bacterial brain microbiome. We profiled the bacterial communities present in non-demented controls and AD subjects’ brains.ResultsWe obtained post-mortem samples from the brains of 32 individual subjects, comprising 16 AD and 16 control aged-matched subjects with a total of 130 samples from the frontal and temporal lobes and entorhinal cortex. We used full-length 16S rRNA gene amplification with Pacific Biosciences sequencing technology to identify the bacteria.We detected bacteria in the brains of both cohorts with the principal bacteria comprisingPropionibacterium acnes(recently renamedCutibacterium acnes)and two species each ofAcinetobacterandComamonasgenera. We used a hierarchical Bayesian method to detect differences in relative abundance among AD and control groups. Because of large abundance variances we also employed an unconventional analysis approach that utilized Latent Dirichlet Allocation, often used in computational linguistics. This allowed us to identify 5 classes of samples, each revealing a different microbiome. Assuming that samples represented infections that potentially began at different times, we ordered these classes in time, finding that the last class exclusively explained the existence or non-existence of AD.ConclusionsThe AD-related pathogenicity of the brain microbiome seems to be based on a complex polymicrobial dynamic. The time ordering revealed a rise and fall of the abundance ofPropionibacterium acneswith pathogenicity occurring for an off-peak abundance level in association with at least one other bacterium from a set of genera that included:Methylobacterium, Bacillus, Caulobacter, Delftia,andVariovorax. P. acnesmay also be involved with outcompeting theComamonasspecies, which were strongly associated with non-demented brain microbiome, whose early destruction could be the first stage of the disease. The statistical results are also consistent with a leaky blood brain barrier or lymphatic network that allows bacteria, viruses, fungi, or other pathogens to enter the brain.
Local Field Potentials, Spiking Activity, and Receptive Fields in Human Visual Cortex
Authors: Luo Lu , Wang Xiongfei , Lu Junshi , Chen Guanpeng , Luan Guoming , Li Wu , Wang Qian , Fang Fang 
Published: August 2022

SUMMARYThe concept of receptive field (RF) is central to sensory neuroscience. Neuronal RF properties have been substantially studied in animals, while those in humans remain nearly unexplored. Here, we measured neuronal RFs with intracranial local field potentials (LFPs) and spiking activity in human visual cortex (V1/V2/V3). We recorded LFPs via macro-contacts and discovered that RF sizes estimated from low-frequency activity (LFA, 0.5 – 30 Hz) were larger than those estimated from low-gamma activity (LGA, 30 – 60 Hz) and high-gamma activity (HGA, 60 – 150 Hz). We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously. We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity. In sum, this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement, implying the pivotal functions of LGA and HGA in early visual information processing.
Redox signaling regulates breast cancer metastasis via HIF1α-stimulated EMT dynamics and metabolic reprogramming
Authors: Ren Zuen , Dharmaratne Malindrie , Liang Huizhi , Benard Outhiriaradjou , Morales-Gallego Miriam , Suyama Kimita , Fard Atefeh Taherian , Mar Jessica C. , Prystowsky Michael , Norton Larry , Hazan Rachel B. 
Published: August 2022

AbstractMetastasis is orchestrated by phenotypic and metabolic reprogramming underlying tumor aggressiveness. Redox signaling by mammary tumor knockdown (KD) of the antioxidant glutathione peroxidase 2 (GPx2) enhanced metastasis via dynamic changes in epithelial-to-mesenchymal transition. Single cell RNA sequencing (scRNA-seq) of the control and PyMT/GPx2 KD mammary tumor revealed six luminal and one basal/mesenchymal like (cluster 3) subpopulations. Remarkably, GPx2 KD enhanced the size and basal/mesenchymal gene signature of cluster 3 as well as induced epithelial/mesenchymal (E/M) clusters which expressed markers of oxidative phosphorylation and glycolysis, indicative of hybrid metabolism. These data were validated in human breast cancer xenografts and were supported by pseudotime cell trajectory analysis. Moreover, the E/M and M states were both attenuated by GPx2 gain of function or HIF1α inhibition, leading to metastasis suppression. Collectively, these results demonstrate that redox/HIF1α signaling promotes mesenchymal gene expression, resulting in E/M clusters and a mesenchymal root subpopulation, driving phenotypic and metabolic heterogeneity underlying metastasis.SignificanceBy leveraging single cell RNA analysis, we were able to demonstrate that redox signaling by GPx2 loss in mammary tumors results in HIF1α signaling, which promotes partial and full EMT conversions, represented by distinct tumor cell subpopulations, which in turn express hybrid and binary metabolic states. These data underscore a phenotypic and metabolic co-adaptation in cancer, arguing in favor of the GPx2-HIF1α axis as a therapeutic platform for targeting tumor cell metastasis.
A low dimensional cognitive-network space in Alzheimer’s disease and frontotemporal dementia
Authors: Pini Lorenzo , de Lange Siemon , Pizzini Francesca , Galazzo Ilaria Boscolo , Manenti Rosa , Cotelli Maria , Galluzzi Samantha , Cotelli Maria Sofia , Corbetta Maurizio , Van den Heuvel Martijn , Pievani Michela 
Published: August 2022

AbstractNetwork neuroscience is a promising approach to explore cognitive processes in neurological disorders. Alzheimer’s disease (AD) and frontotemporal dementia (FTD) show network dysfunctions linked with cognitive deficits. Within this framework, network abnormalities between AD and FTD show both convergent and divergent patterns. However, these functional patterns are far from being established and their relevance to cognitive processes remains to be elucidated. In this study, we aimed to investigate the relationship between cognition and functional connectivity of major cognitive networks in these diseases. Twenty-three bvFTD (age: 71±10), 22 AD (age: 72±6) and 20 controls (age: 72±6) underwent cognitive evaluation and resting-state functional MRI. Principal component analysis was used to describe cognitive variance across participants. Brain network connectivity was estimated with connectome analysis. Connectivity matrices were created assessing correlations between parcels within each functional network. The following cognitive networks were considered: default mode (DMN), dorsal attention (DAN), ventral attention (VAN) and frontoparietal (FPN) networks. The relationship between cognition and connectivity was assessed using a robust convergent correlation-wise and interaction analyses. Three principal cognitive components explained more than 80% of the cognitive variance: the first component (cogPC1) loaded on memory, the second component (cogPC2) loaded on emotion and language, the third component (cogPC3) loaded on the visuo-spatial and attentional domains. Compared to HC, AD and bvFTD showed impairment in all cogPCs (p<0.002), and bvFTD scored worse than AD in cogPC2 (p=0.031). At the network level, the DMN showed a robust association in the whole group with cogPC1 and cogPC2, and the VAN with cogPC2. By contrast, DAN and FPN showed a divergent pattern between diagnosis and connectivity for cogPC2. We confirmed these results by means of a multivariate analysis (canonical correlation). These results suggest that a low-dimensional representation can account for a large variance in cognitive scores in the continuum from normal to pathological aging. Moreover, cognitive components showed both convergent and divergent patterns with connectivity across AD and bvFTD. The convergent pattern was observed across the networks primarily involved in these diseases (i.e., the DMN and VAN), while a divergent FC-cognitive pattern was mainly observed between attention/executive networks and the language/emotion cognitive component, suggesting the co-existence of compensatory and detrimental mechanisms underlying these components.
Two sides to every coin: reciprocal introgression line populations inCaenorhabditis elegans
Authors: Sterken Mark G. , van Sluijs Lisa , van Creij Jelle W. , Cook Daniel E. , Riksen Joost A.G. , Jovic Katharina , Schouten Jasmijn , Steeghs Maarten , Wang Yiru A. , Stastna Jana J. , Snoek L. Basten , Harvey Simon C. , Kammenga Jan E. 
Published: August 2022

AbstractQuantitative genetics seeks to understand the role of allelic variation in trait differences. Introgression lines (ILs) contain a single genetic locus introgressed into another genetic background, and are one of the most powerful quantitative trait locus (QTL) mapping designs. However, albeit useful for QTL discovery, this homogenous background confounds genetic interactions. Here, we created an IL population with N2 segments in a CB4856 background (ILCB4856), reciprocal to an N2 background with CB4856 introgressions population (ILN2). The ILCB4856panel comprises a population of 145 strains with sequencing confirmed N2 introgressions in a CB4856 background. A core set of 87 strains covering the entire genome was selected. We present three experiments demonstrating the power of the reciprocal IL panels. First, we performed QTL mapping identifying new regions associated with lifespan. Second, the existence of opposite-effect loci regulating heat-stress survival is demonstrated. Third, by combining ILN2and ILCB4856strains, an interacting expression QTL was uncovered. In conclusion, the reciprocal IL panels are a unique and ready-to-use resource to identify, resolve, and refine complex trait architectures inC. elegans.