bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating Genetic and Transcriptomic Data to Identify Genes Underlying Obesity Risk Loci
Authors: Xu Hanfei , Gupta Shreyash , Dinsmore Ian , Kollu Abbey , Cawley Anne Marie , Anwar Mohammad Y. , Chen Hung-Hsin , Petty Lauren E. , Seshadri Sudha , Graff Misa , Below Piper , Brody Jennifer A. , Chittoor Geetha , Fisher-Hoch Susan P. , Heard-Costa Nancy L. , Levy Daniel , Lin Honghuang , Loos Ruth JF. , Mccormick Joseph B. , Rotter Jerome I. , Mirshahi Tooraj , Still Christopher D. , Destefano Anita , Cupples L. Adrienne , Mohlke Karen L , North Kari E. , Justice Anne E. , Liu Ching-Ti 
Published: June 2024

ABSTRACTGenome-wide association studies (GWAS) have identified numerous body mass index (BMI) loci. However, most underlying mechanisms from risk locus to BMI remain unknown. Leveraging omics data through integrative analyses could provide more comprehensive views of biological pathways on BMI. We analyzed genotype and blood gene expression data in up to 5,619 samples from the Framingham Heart Study (FHS). Using 3,992 single nucleotide polymorphisms (SNPs) at 97 BMI loci and 20,692 transcripts within 1 Mb, we performed separate association analyses of transcript with BMI and SNP with transcript (PBMIand PSNP, respectively) and then a correlated meta-analysis between the full summary data sets (PMETA). We identified transcripts that met Bonferroni-corrected significance for each omic, were more significant in the correlated meta-analysis than each omic, and were at least nominally associated with BMI in FHS data. Among 308 significant SNP-transcript-BMI associations, we identified seven genes (NT5C2,GSTM3,SNAPC3,SPNS1,TMEM245,YPEL3, andZNF646) in five association regions. Using an independent sample of blood gene expression data, we validated results forSNAPC3andYPEL3. We tested for generalization of these associations in hypothalamus, nucleus accumbens, and liver and observed significant (PMETA<0.05 & PMETA<PSNP& PMETA<PBMI) results forYPEL3in nucleus accumbens andNT5C2,SNAPC3,TMEM245,YPEL3, andZNF646in liver. The identified genes help link the genetic variation at obesity risk loci to biological mechanisms and health outcomes, thus translating GWAS findings to function.
A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among TNFSF superfamily in breast cancer
Authors: Moradi Abolfazl , Vafadar Esfahani Farinaz , Mohammadian Ali 
Published: June 2024

AbstractBreast cancer (BC) is one of most important mortality factors among women therefore to find important genes in BC can help early diagnosis, treatment or prevention.TNFSFor tumor necrosis factor Superfamily have an important role in various cancers. In BC, some of studies have found dual roles for these genes. In this research, we conducted a comprehensive and detailed bioinformatics study on this family. UALCAN, TNMplot, UCSC Xena, GEPIA, The Human Protein Atlas, Kaplan–Meier plotter, bc-GenExMiner, cBioPortal, STRING, GeneMANIA, Enrichr, TIMER and shinyDepMap were used for analysis. We found that these genes play their role through the immune system and the high expression of eightFASLG, LTB, TNF, TNFSF8, TNFSF10, TNFSF11, TNFSF12, TNFSF13genes were positively associated with OS and RFS. Overall, our data showed that these genes can be considered as prognostic biomarkers. Further, our results suggest that this family has anti-tumor activity.
Geospatial analysis of malaria burden in Kagera region, North-western Tanzania using health facility and community survey data
Authors: Petro Daniel A. , Shaban Nyimvua , Aaron Sijenunu , Chacky Frank , Lazaro Samwel , Boni Maciej F. , Ishengoma Deus S. 
Published: June 2024

AbstractGenerating evidence of malaria burden in areas with confirmed artemisinin partial resistance (ART-R) is the first step before developing a response strategy to the resistance. In this study, we assessed the burden of malaria in Kagera region (with recently confirmed ART-R) by geospatial analysis using data from health facilities (HFs) and community surveys from 2017 to 2023. In 2983717/8124363 patients from HFs, rapid diagnostic test positivity rate was 36.7% (range: 0-80%) and was similar in patients aged under-fives (33.1%, range: 0-79%) and ≥5 years (33.7%, range: 3-80%). The prevalence of malaria was 10.0% (range: 0-40.5%, n=84999/ 853761) in pregnant women but it was 26.1% (3409/13065) in school children (range: 0-78.4%). We identified hotspots and coldspots, and persistently high burden in 69/192 wards, school children, and patients aged ≥5 years, providing evidence for planning and developing an ART-R response for the region.
Viral diversiy within marine biofilms and their potential roles in microbially influenced corrosion
Authors: Li Chengpeng , Zhang Yimeng , Jiang Shuqing , Shi Wenqing , Peng Yongyi , Han Yingchun , Dong Xiyang , Zhang Ruiyong 
Published: June 2024

AbstractIn marine environments, a wide variety of microbes exert an important influence on the corrosion of materials. Viruses are widely distributed in biofilms formed on materials and may influence the corrosion process through interactions with key corrosive microbes. However, our understanding of the viral communities within biofilms and their implications for corrosion remains notably limited. To fill this knowledge gap, we utilized 53 publicly metagenomes to investigate the ecological dynamics of viruses within biofilms on 8 different materials and their potential roles in the corrosion of materials. In biofilms, the type of materials may be the primary factor driving differences in the diversity of viral communities. Viruses within biofilms predominantly belong toCaudoviricetes,and phylogenetic analysis ofCaudoviricetesand protein-sharing networks with other environments revealed the presence of numerous novel viral clades in biofilms. The presence of virus‒host linkages revealed a close association between viruses and corrosive microbes in biofilms. Viruses play a key role in corrosion by modulating host corrosion-related metabolism. It was observed that viruses could enhance host resistance to metals and antibiotics via horizontal gene transfer. Furthermore, viruses can protect themselves from host antiviral systems through anti-defense systems. Overall, this work illustrates the diversity of viruses within biofilms formed on materials and the intricate interactions between viruses and corrosive microbes, revealing the potential roles of viruses in microbially influenced corrosion.
Analysis-ready VCF at Biobank scale using Zarr
Authors: Czech Eric , Millar Timothy R. , Tyler Will , White Tom , Elsworth Benjamin , Guez Jérémy , Hancox Jonny , Jeffery Ben , Karczewski Konrad J. , Miles Alistair , Tallman Sam , Unneberg Per , Wojdyla Rafal , Zabad Shadi , Hammerbacher Jeff , Kelleher Jerome 
Published: June 2024

AbstractBackgroundVariant Call Format (VCF) is the standard file format for interchanging genetic variation data and associated quality control metrics. The usual row-wise encoding of the VCF data model (either as text or packed binary) emphasises efficient retrieval of all data for a given variant, but accessing data on a field or sample basis is inefficient. Biobank scale datasets currently available consist of hundreds of thousands of whole genomes and hundreds of terabytes of compressed VCF. Row-wise data storage is fundamentally unsuitable and a more scalable approach is needed.ResultsZarr is a format for storing multi-dimensional data that is widely used across the sciences, and is ideally suited to massively parallel processing. We present the VCF Zarr specification, an encoding of the VCF data model using Zarr, along with fundamental software infrastructure for efficient and reliable conversion at scale. We show how this format is far more efficient than standard VCF based approaches, and competitive with specialised methods for storing genotype data in terms of compression ratios and single-threaded calculation performance. We present case studies on subsets of three large human datasets (Genomics England:n=78,195; Our Future Health:n=651,050; All of Us:n=245,394) along with whole genome datasets for Norway Spruce (n=1,063) and SARS-CoV-2 (n=4,484,157). We demonstrate the potential for VCF Zarr to enable a new generation of high-performance and cost-effective applications via illustrative examples using cloud computing and GPUs.ConclusionsLarge row-encoded VCF files are a major bottleneck for current research, and storing and processing these files incurs a substantial cost. The VCF Zarr specification, building on widely-used, open-source technologies has the potential to greatly reduce these costs, and may enable a diverse ecosystem of next-generation tools for analysing genetic variation data directly from cloud-based object stores, while maintaining compatibility with existing file-oriented workflows.Key PointsVCF is widely supported, and the underlying data model entrenched in bioinformatics pipelines.The standard row-wise encoding as text (or binary) is inherently inefficient for large-scale data processing.The Zarr format provides an efficient solution, by encoding fields in the VCF separately in chunk-compressed binary format.
Massively Parallel Reporter Assays identify enhancer elements in Oesophageal Adenocarcinoma
Authors: Yang SH , Ahmed I , Li Y , Bleaney CW , Sharrocks AD 
Published: June 2024

AbstractCancer is a disease underpinned by aberrant gene expression. Enhancers are regulatory elements that play a major role in transcriptional control and changes in active enhancer function are likely critical in the pathogenesis of oesophageal adenocarcinoma (OAC). Here, we utilise STARR-seq to profile the genome-wide enhancer landscape in OAC and identify hundreds of high-confidence enhancer elements. These regions are enriched in enhancer-associated chromatin marks, are actively transcribed and exhibit high levels of associated gene activity in OAC cells. These characteristics are maintained in human patient samples, demonstrating their disease relevance. This relevance is further underlined by their responsiveness to oncogenic ERBB2 inhibition and increased activity compared to the pre-cancerous Barrett’s state. Mechanistically, these enhancers are linked to the core OAC transcriptional network and in particular KLF5 binding is associated with high level activity, providing further support for a role of this transcription factor in defining the OAC transcriptome. Our results therefore uncover a set of enhancer elements with physiological significance, that widen our understanding of the molecular alterations in OAC and point to mechanisms through which response to targeted therapy may occur.
Echo-locate: Cerebellar activity predicts vocalization in fruit-eating bats
Authors: Hariharan Shivani , González Palomares Eugenia , Hechavarria Julio C. 
Published: June 2024

AbstractEcholocating bats exhibit remarkable auditory behaviors, enabled by adaptations within and outside their auditory system. Yet, research in echolocating bats has focused mostly on brain areas that belong to the classic ascending auditory pathway. This study provides direct evidence linking the cerebellum, an evolutionarily ancient and non-classic auditory structure, to vocalization and hearing. We report that in the fruit-eating batCarollia perspicillata, external sounds can evoke cerebellar responses with latencies below 20 ms. Such fast responses are indicative of early inputs to the bat cerebellum. In vocalizing bats, distinct spike train patterns allow the prediction with over 85% accuracy of the sound they are about to produce, or have just produced, i.e., communication calls or echolocation pulses. Taken together, our findings provide evidence of specializations for vocalization and hearing in the cerebellum of an auditory specialist.TeaserThe cerebellum of fruit-eating bats responds to sounds and predicts future and past vocalizations
Palytoxin Evokes Reversible Spreading Depolarization in the Locust CNS
Authors: Wang Yuyang , Van Dusen Rachel A. , McGuire Catherine , Andrew R. David , Robertson R. Meldrum 
Published: June 2024

AbstractSpreading depolarization (SD) describes the near-complete depolarization of CNS neural cells as a consequence of chemical, electrical, and metabolic perturbations. It is well-established as the central mechanism underlying insect coma and various mammalian neurological dysfunctions. Despite significant progress in our understanding, the question remains: which cation channel, if any, generates SD in the CNS?Previously, we speculated that the sodium-potassium ATPase (NKA) might function as a large-conductance ion channel to initiate SD in insects, potentially mediated by a palytoxin (PLTX)-like endogenous activator. In the current study, we evaluate the effectiveness and properties of PLTX as an SD initiator inL. migratoria. Whereas bath-applied PLTX failed to ignite SD, direct injection into the neuropil triggered SD in 57% of the preparations. Notably, PLTX-induced SD onset was significantly more rapid compared to ouabain injection and azide controls, though their electrophysiological features remained similar. Furthermore, PLTX-induced SD was recoverable and resulted in a greater frequency of repetitive SD events compared to ouabain.Surprisingly, prior PLTX treatment disrupted the onset and recovery of subsequent SD evoked by other means. PLTX injection could attenuate the amplitude and hasten the onset time of azide-induced SD. Such an effect is associated with a complete inhibition at higher doses of subsequent anoxic SD induced through azide treatment or submersion.These results show that PLTX can trigger repetitive and reversible SD-like events in locusts and simultaneously interfere with anoxic SD occurrence. We suggest that the well-documented NKA pump conversion into an open non-selective cationic channel is a plausible mechanism of SD activation in the locust CNS, warranting additional investigations.
MultiGreen: A multiplexing architecture for GreenGate cloning
Authors: Pennetti Vincent J. , LaFayette Peter R. , Parrott Wayne Allen 
Published: June 2024

AbstractGenetic modification of plants fundamentally relies upon customized vector designs. The ever-increasing complexity of transgenic constructs has led to increased adoption of modular cloning systems for their ease of use, cost effectiveness, and rapid prototyping. GreenGate is a modular cloning system catered specifically to designing bespoke, single transcriptional unit vectors for plant transformation— which is also its greatest flaw. MultiGreen seeks to address GreenGate’s limitations while maintaining the syntax of the original GreenGate kit. The primary limitations MultiGreen addresses are 1) multiplexing in series, 2) multiplexing in parallel, and 3) repeated cycling of transcriptional unit assembly through binary intermediates. MultiGreen efficiently concatenates bespoke transcriptional units using an additional suite of level 1acceptor vectors which serve as an assembly point for individual transcriptional units prior to final, level 2, condensation of multiple transcriptional units. Assembly with MultiGreen level 1 vectors scales at a maximal rate of 2*⌈log6n⌉+3 days per assembly, wherenrepresents the number of transcriptional units. Further, MultiGreen level 1 acceptor vectors are binary vectors and can be used directly for plant transformation to further maximize prototyping speed. MultiGreen is a 1:1 expansion of the original GreenGate architecture’s grammar and has been demonstrated to efficiently assemble plasmids with multiple transcriptional units. MultiGreen has been validated by using a truncated violacein operon fromChromobacterium violaceumin bacteria and by deconstructing the RUBY reporter forin plantafunctional validation. MultiGreen currently supports many of our in-house multi transcriptional unit assemblies and will be a valuable strategy for more complex cloning projects.
Vertical transmission of fungus-growing ant microbiota is species-specific and constrained by queens
Authors: Sadowski Victoria A. , Sapountzis Panagiotis , Kooij Pepijn W. , Boomsma Jacobus J. , Adams Rachelle M.M. 
Published: June 2024

AbstractMultipartite symbioses are inherently complex, involving dynamic ecological interactions between organisms with intertwined yet distinct evolutionary histories. The fungus-growing (attine) ants facilitate maintenance of a symbiotic species network through maternal vertical transmission of an obligate fungal symbiont. While the gut microbiomes of fungus-growing ant species are remarkably simple, their fungal gardens support diverse microbial communities. Here, we focus on an understudied transmission bottleneck: the fungal garden pellet that nest-founding queens transfer to inoculate a new fungal garden. We used 16S rRNA metagenomic sequencing to reconstruct the extent of vertical transmission of bacteria to new gardens via queen pellets in four sympatric fungus-growing ant species (Atta sexdens,Atta cephalotes,Acromyrmex echinatior, andMycetomoellerius mikromelanos) from Central Panama. We also characterized the bacterial communities associated with queen eggs and somatic tissues (mesosomas, guts and ovaries) to assess whether queens are likely to transmit symbiotic bacteria of workers, such as cuticular Actinobacteria and endosymbionts (Wolbachia,Mesoplasma, andSpiroplasma). Our results suggest that garden-associated bacteria are mainly horizontally acquired as the bacterial communities of pellets shared few bacterial taxa with the mature gardens of the four ant species investigated. While the bacterial communities of garden pellets showed some species-specificity, a subset of prevalent bacterial taxa were shared across ant species. Further, our findings provide evidence for vertical transmission of species-specific endosymbiotic bacteria through a transovarial route and/or via fecal droplets. Overall, while we found mixed evidence for vertical transmission of garden bacteria, our results support maternal transmission as a primary route for gut-associated symbionts. While our results suggest that vertical transmission of fungus-growing ant bacterial associates is mediated by the ant hosts, the mechanism behind this host control is not yet understood.
Tracking tree demography and forest dynamics at scale using remote sensing
Authors: Battison Robin , Prober Suzanne M. , Zdunic Katherine , Jackson Toby D. , Fischer Fabian Jörg , Jucker Tommaso 
Published: June 2024

SUMMARYCapturing how tree growth and survival vary through space and time is critical to understanding the structure and dynamics of tree-dominated ecosystems. However, characterising demographic processes at scale is inherently challenging, as trees are slow-growing, long-lived, and cover vast expanses of land.We used repeat airborne laser scanning data acquired over 25 km2of semi-arid, old-growth temperate woodland in Western Australia to track the height growth, crown expansion and mortality of 42,810 individual trees over nine years.We found that demographic rates are constrained by a combination of tree size, competition and topography. After initially investing in height growth, trees progressively shifted to crown expansion as they grew larger, while mortality risk decreased considerably with size. Across the landscape, both tree growth and survival increased with topographic wetness, resulting in vegetation patterns that are strongly spatially structured. Moreover, biomass gains from woody growth generally outpaced losses from mortality, suggesting these old-growth woodlands remain a net carbon sink in the absence of wildfires.Our study sheds new light on the processes that shape the dynamics and spatial structure of semi-arid woody ecosystems and provides a roadmap for using emerging remote sensing technologies to track tree demography at scale.
Grapevine vigour: a critical factor driving Trunk Disease expression
Authors: Claverie Marion , Audras Maïko , Berud François , Richy Didier 
Published: June 2024

AbstractEsca and Black Dead Arm (EBDA) are complex grapevine trunk diseases (GTD) that are major causes of mortality and production decline in French vineyards. Unravelling the different factors that determine symptom expression is crucial in mitigating the impact on growers. While cultivar, climate, age, and pruning system are known contributors, they do not fully explain the variability in EBDA occurrence. This study investigates the role of grapevine vigour as a determinant factor in EBDA expression.In 2022 and 2023, three vineyard networks were monitored, each consisting of approximately 30 vineyard plots of Grenache Noir, uniform in age. To minimize climate variation the selected vineyards were located within small geographical areas. We evaluated grapevine vigour and its primary drivers—water and nitrogen status, weed cover, production, and vegetation biomass—and correlated these factors with EBDA occurrence.Results show that current-year vigour is positively correlated with the EBDA incidence rate in all network*year scenarios. The relationship curve suggests that, while low to moderate vigour is consistently associated with reduced symptom expression, high vigour can be correlated with either high or low expression and implies the involvement of additional factors. In one instance, previous year water stress, of all tested variables, was most correlated with current year EBDA incidence, though vigour was also influential. In that case, EBDA expression seems to be maximal when water stress the year before is combined with a substantial current year spring vigour. While these results need to be confirmed over a longer period, in more regions and with other cultivars, they open new perspectives of applications for growers. They suggest a wider implication of grapevine physiology than just vigour.