bluuebunny/crossref_metadata_2025_split huggingface dataset:
A difference in larval mosquito size allows a biocontrol agent to target the invasive species
Authors: Russell Marie C. 
Published: March 2023

AbstractAs the global temperature rises in the coming decades,Aedes albopictusis expected to invade and establish in South East England, whereCulex pipiensis currently the most common native mosquito species. Biocontrol measures that use local cyclopoid copepods againstAe. albopictusmay be compromised if the copepods prefer alternateCx. pipiensprey. In this study, we assessed the predation efficiency ofMegacyclops viridiscopepods against FrenchAe. albopictuslarvae and larvae that hatched from egg rafts ofCx. pipienscollected in South East England. The experiments were conducted at 15°C and 25°C, which are representative of present and future summer temperatures in South East England.Ae. albopictuslarvae that survived the course of the experiment in the predator-absent controls were significantly smaller thanCx. pipienslarvae that survived in the absence of predation. The background mortality ofCx. pipienslarvae increased with the ten-degree increase in temperature, and the smaller size of survivingCx. pipienslarvae at 25°C, relative to survivors at 15°C, suggests that largerCx. pipienslarvae were more likely to die at the higher temperature setting. Across all experimental treatments, the ratio of copepod body length to mean prey length, based on larval lengths of survivors from the corresponding predator-absent controls, was a significant predictor of predation efficiency. Adding temperature setting to the predation efficiency model as a predictor did not improve model fit. Within the mixed prey treatments, the predation efficiency ofM. viridiswas 34.5 percentage points higher againstAe. albopictusprey than againstCx. pipiensprey. The higher predation efficiency thatM. viridisexhibited against invasiveAe. albopictusprey, likely due to the smaller size of these larvae, supports the future use ofM. viridisas a biocontrol agent in the UK.
Prophage maintenance is determined by environment-dependent selective sweeps rather than mutational availability
Authors: Bailey Zachary M. , Igler Claudia , Wendling Carolin C. 
Published: March 2023

AbstractProphages, viral sequences integrated into bacterial genomes, can be beneficial and costly. Despite the risk of prophage activation and subsequent bacterial death, active prophages are present in most bacterial genomes. However, our understanding of the selective forces that maintain prophages in bacterial populations is limited. Combining experimental evolution with stochastic modelling, we show that prophage maintenance and loss are primarily determined by environmental conditions that alter the net fitness effect of a prophage. When prophages are too costly, they are rapidly lost through environment-specific sequences of selective sweeps. Conflicting selection pressures that select against the prophage but for a prophage-encoded accessory gene can maintain prophages. The dynamics of prophage maintenance additionally depends on the sociality of this accessory gene. Non-cooperative genes maintain prophages at higher frequencies than cooperative genes, which can protect phage-free ‘cheaters’ that may emerge if prophage costs outweigh their benefits. Our simulations suggest that environmental variation plays a larger role than mutation rates in determining prophage maintenance. These findings highlight the complexity of selection pressures that act on mobile genetic elements and challenge our understanding of the role of environmental factors relative to random chance events in shaping the evolutionary trajectory of bacterial populations.
A cortical surface template for human neuroscience
Authors: Feilong Ma , Jiahui Guo , Gobbini M. Ida , Haxby James V. 
Published: March 2023

AbstractNeuroimaging data analysis relies on normalization to standard anatomical templates to resolve macroanatomical differences across brains. Existing human cortical surface templates sample locations unevenly because of distortions introduced by inflation of the folded cortex into a standard shape. Here we present the onavg template, which affords uniform sampling of the cortex. We created the onavg template based on openly-available high-quality structural scans of 1,031 brains—25 times more than existing cortical templates. We optimized the vertex locations based on cortical anatomy, achieving an even distribution. We observed consistently higher multivariate pattern classification accuracies and representational geometry inter-subject correlations based on onavg than on other templates, and onavg only needs 3⁄4 as much data to achieve the same performance compared to other templates. The optimized sampling also reduces CPU time across algorithms by 1.3%–22.4% due to less variation in the number of vertices in each searchlight.
Cell-type specific EWAS identifies genes involved in HIV pathogenesis and oncogenesis among people with HIV infection
Authors: Zhang Xinyu , Hu Ying , Vandenhoudt Ral E. , Yan Chunhua , Marconi Vincent C , Cohen Mardge H. , Justice Amy C , Aouizerat Bradley E , Xu Ke 
Published: March 2023

AbstractEpigenome-wide association studies (EWAS) of heterogenous blood cells have identified CpG sites associated with chronic HIV infection, which offer limited knowledge of cell-type specific methylation patterns associated with HIV infection. Applying a computational deconvolution method validated by capture bisulfite DNA methylation sequencing, we conducted a cell type-based EWAS and identified differentially methylated CpG sites specific for chronic HIV infection among five immune cell types in blood: CD4+ T-cells, CD8+ T-cells, B cells, Natural Killer (NK) cells, and monocytes in two independent cohorts (Ntotal=1,134). Differentially methylated CpG sites for HIV-infection were highly concordant between the two cohorts. Cell-type level meta-EWAS revealed distinct patterns of HIV-associated differential CpG methylation, where 67% of CpG sites were unique to individual cell types (false discovery rate, FDR <0.05). CD4+ T-cells had the largest number of HIV-associated CpG sites (N=1,472) compared to any other cell type. Genes harboring statistically significant CpG sites are involved in immunity and HIV pathogenesis (e.g.CX3CR1in CD4+ T-cells,CCR7in B cells,IL12Rin NK cells,LCKin monocytes). More importantly, HIV-associated CpG sites were overrepresented for hallmark genes involved in cancer pathology (FDR<0.05) (e.g.BCL family, PRDM16, PDCD1LGD, ESR1, DNMT3A, NOTCH2). HIV-associated CpG sites were enriched among genes involved in HIV pathogenesis and oncogenesis such as Kras-signaling, interferon-α and −γ, TNF-α, inflammatory, and apoptotic pathways. Our findings are novel, uncovering cell-type specific modifications in the host epigenome for people with HIV that contribute to the growing body of evidence regarding pathogen-induced epigenetic oncogenicity, specifically on HIV and its comorbidity with cancers.
Dimension-agnostic and granularity-based spatially variable gene identification
Authors: Wang Juexin , Li Jinpu , Kramer Skyler T , Su Li , Chang Yuzhou , Xu Chunhui , Ma Qin , Xu Dong 
Published: March 2023

AbstractIdentifying spatially variable genes (SVGs) is critical in linking molecular cell functions with tissue phenotypes. Spatially resolved transcriptomics captures cellular-level gene expression with corresponding spatial coordinates in two or three dimensions and can be used to infer SVGs effectively. However, current computational methods may not achieve reliable results and often cannot handle three-dimensional spatial transcriptomic data. Here we introduce BSP (big-small patch), a spatial granularity-guided and non-parametric model to identify SVGs from two or three-dimensional spatial transcriptomics data in a fast and robust manner. This new method has been extensively tested in simulations, demonstrating superior accuracy, robustness, and high efficiency. BSP is further validated by substantiated biological discoveries in cancer, neural science, rheumatoid arthritis, and kidney studies with various types of spatial transcriptomics technologies.
Integrating long-read RNA sequencing improves locus-specific quantification of transposable element expression
Authors: Lee Sojung , Barbour Jayne A. , Tam Yee Man , Yang Haocheng , Huang Yuanhua , Wong Jason W. H. 
Published: March 2023

AbstractTransposable elements (TEs) can influence human diseases by disrupting genome integrity, yet their quantification has been challenging due to the repetitive nature of these sequences across the genome. We developed LocusMasterTE, a method that integrates long-read with short-read RNA-seq to increase the accuracy of TE expression quantification. By incorporating fractional transcript per million (TPM) values from long-read sequencing data into an expectation-maximization (EM) algorithm, LocusMasterTE reassigns multi-mapped reads, enhancing accuracy in short-read-based TE quantification. Validated with simulated and human datasets, LocusMasterTE holds promise for revealing new insights into TE functions through precise quantification.
Proximity Proteome Analysis Reveals Novel TREM2 Interactors in the ER-Mitochondria Interface of Human Microglia
Authors: Kwak Chulhwan , Finan Gina M. , Park Yu Rim , Garg Anjali , Harari Oscar , Mun Ji Young , Rhee Hyun-Woo , Kim Tae-Wan 
Published: March 2023

AbstractTriggering receptor expressed on myeloid cells 2 (TREM2) plays a central role in microglial biology and the pathogenesis of Alzheimer’s disease (AD). Besides DNAX-activating protein 12 (DAP12), a communal adaptor for TREM2 and many other receptors, other cellular interactors of TREM2 remain largely elusive. We employed a ‘proximity labeling’ approach using a biotin ligase, TurboID, for mapping protein–protein interactions in live mammalian cells. We discovered novel TREM2-proximal proteins with diverse functions, including those localized to the Mitochondria-ER contact sites (MERCs), a dynamic subcellular ‘hub’ implicated in a number of crucial cell physiology such as lipid metabolism. TREM2 deficiency alters the thickness (inter-organelle distance) of MERCs, a structural parameter of metabolic state, in microglia derived from human induced pluripotent stem cells. Our TurboID-based TREM2 interactome study suggest novel roles for TREM2 in the structural plasticity of the MERCs, raising the possibility that dysregulation of MERC-related TREM2 functions contribute to AD pathobiology.
Lightweight Fine-tuning a Pretrained Protein Language Model for Protein Secondary Structure Prediction
Authors: Yang Wei , Liu Chun , Li Zheng 
Published: March 2023

AbstractPretrained large-scale protein language models, such as ESM-1b and ProtTrans, are becoming the fundamental infrastructure for various protein-related biological modeling tasks. Existing works use mainly pretrained protein language models in feature extraction. However, the knowledge contained in the embedding features directly extracted from a pretrained model is task-agnostic. To obtain task-specific feature representations, a reasonable approach is to fine-tune a pretrained model based on labeled datasets from downstream tasks. To this end, we investigate the fine-tuning of a given pretrained protein language model for protein secondary structure prediction tasks. Specifically, we propose a novel end-to-end protein secondary structure prediction framework involving the lightweight fine-tuning of a pretrained model. The framework first introduces a few new parameters for each transformer block in the pretrained model, then updates only the newly introduced parameters, and then keeps the original pretrained parameters fixed during training. Extensive experiments on seven test sets, namely, CASP12, CASP13, CASP14, CB433, CB634, TEST2016, and TEST2018, show that the proposed framework outperforms existing predictors and achieves new state-of-the-art prediction performance. Furthermore, we also experimentally demonstrate that lightweight fine-tuning significantly outperforms full model fine-tuning and feature extraction in enabling models to predict secondary structures. Further analysis indicates that only a few top transformer blocks need to introduce new parameters, while skipping many lower transformer blocks has little impact on the prediction accuracy of secondary structures.
Transient demographic dynamics of recovering fish populations shaped by past climate variability, harvest, and management
Authors: Goto Daisuke 
Published: March 2023

AbstractLarge-scale commercial harvesting and climate-induced fluctuations in ocean properties shape the dynamics of marine populations as interdependent drivers at varied timescales. Selective removals of larger, older members of a population can distort its demographic structure, eroding resilience to fluctuations in habitat conditions and thus amplifying volatility in transient dynamics. Through the implementation of stricter management measures, many historically depleted fish stocks began showing signs of recovery in recent decades. But these interventions coincided with accelerated changes in the oceans triggered by increasingly warmer, more variable climates. Applying multilevel models to annual estimates of demographic metrics of 38 stocks comprising 11 species across seven ecoregions in the northeast Atlantic Ocean, this study explores how time-varying local and regional climates contributed to the transient dynamics of recovering populations exposed to variable fishing pressures moderated by management actions. Analyses reveal that progressive reductions in fishing pressure and shifting climate conditions nonlinearly shaped rebuilding patterns of the stocks through restorations of maternal demographic structure (reversing age truncation) and reproductive capacity. As the survival rate and demographic structure of reproductive fish improved, transient growth became less sensitive to variability in recruitment and juvenile survival and more to that in adult survival. As the biomass of reproductive fish rose, recruitment success also became increasingly regulated by density-dependent processes involving higher numbers of older fish. When reductions in fishing pressure were insufficient or delayed, however, stocks became further depleted, with more eroded demographic structures. Although warmer local climates in spawning seasons promoted recruitment success in some ecoregions, changing climates in recent decades began adversely affecting reproductive performances overall, amplifying sensitivities to recruitment variability. These shared patterns underscore the value of demographic transients in developing robust strategies for managing marine resources. Such strategies could form the foundation for effective applications of adaptive measures resilient to future environmental change.
Chromosome-aware phylogenomics of Assassin Bugs (Hemiptera: Reduvioidea) elucidates ancient gene conflict
Authors: Knyshov Alexander , Gordon Eric R. L. , Masonick Paul K. , Castillo Stephanie , Forero Dimitri , Hoey-Chamberlain Rochelle , Hwang Wei Song , Johnson Kevin P. , Lemmon Alan R. , Lemmon Emily Moriarty , Standring Samantha , Zhang Junxia , Weirauch Christiane 
Published: March 2023

AbstractThough the phylogenetic signal of loci on sex chromosomes can differ from those on autosomes, chromosomal-level genome assemblies for non-vertebrates are still relatively scarce and conservation of chromosomal gene content across deep phylogenetic scales has therefore remained largely unexplored. We here assemble a uniquely large and diverse set of samples (17 Anchored Hybrid Enrichment [AHE], 24 RNA-Seq, and 70 whole-genome sequencing [WGS] samples of variable depth) for the medically important assassin bugs (Reduvioidea). We assess the performance of genes based on multiple features (e.g., nucleotide vs. amino acid, nuclear vs. mitochondrial, and autosomal vs. X chromosomal) and employ different methods (concatenation and coalescence analyses) to reconstruct the unresolved phylogeny of this diverse (∼7,000 spp.) and old (>180 MYA) group. Our results show that genes on the X chromosome are more likely to have discordant phylogenies than those on autosomes. We find that the X chromosome conflict is driven by high gene substitution rates that impact accuracy of phylogenetic inference. However, gene tree clustering showed strong conflict even after discounting variable third codon positions. Alternative topologies were not particularly enriched for sex chromosome loci, but spread across the genome. We conclude that binning genes to autosomal or sex chromosomes may result in a more accurate picture of the complex evolutionary history of a clade.
Cell targeting and immunostimulatory properties of a novel Fcγ-receptor independent agonistic anti-CD40 antibody in rhesus macaques
Authors: Yan Xianglei , Ols Sebastian , Cerveira Rodrigo Arcoverde , Lenart Klara , Hellgren Fredrika , Ye Kewei , Cagigi Alberto , Buggert Marcus , Nimmerjahn Falk , Højen Jesper Falkesgaard , Parera Daniel , Pessara Ulrich , Fischer Stephan , Loré Karin 
Published: March 2023

AbstractTargeting CD40 by agonistic antibodies used as vaccine adjuvants or for cancer immunotherapy is a strategy to stimulate immune responses. The majority of studied agonistic anti-human CD40 antibodies require crosslinking of their Fc region to inhibitory FcγRIIb to induce immune stimulation although this has been associated with toxicity in previous studies. Here we introduce an agonistic anti-human CD40 monoclonal IgG1 antibody (MAB273) unique in its specificity to the CD40L binding site of CD40 but devoid of Fcγ-receptor binding, we demonstrate rapid binding of MAB273 to B cells and dendritic cells resulting in strong activationin vitroon human cells andin vivoin rhesus macaques. Dissemination of fluorescently labeled MAB273 after subcutaneous administration was found predominantly at the site of injection and specific draining lymph nodes. Phenotypic cell differentiation and upregulation of genes associated with immune activation were found in the targeted tissues. Antigen-specific T cell responses were enhanced by MAB273 when given in a prime-boost regimen and for boosting low preexisting responses. MAB273 may therefore be a promising immunostimulatory adjuvant that warrants future testing for therapeutic and prophylactic vaccination strategies.
Dynamics of vegetation cover and its driving factors in the Qinling-Daba Mountains on regional scale for 1986-2019
Authors: Yonghui Yao , Baoguo Wang 
Published: March 2023

AbstractThe Qinling-Daba Mountains is the transitional zone of the north and south of China. The vegetation in this area, characterized by complexity, heterogeneity and transition, is particularly sensitive to global climate change and human activities. Based on the normalized vegetation index (NDVI) data of the growing season from 1986 to 2019, which was synthesized by Landsat series satellite data on Google Earth Engine, this paper uses the methods of spatial analysis and Geo-detectors to clarify dynamics of vegetation cover and its main driving factors in the Qinling-Daba Mountains. The results show that: (1) vegetation coverage in study area shows a U-shaped NDVI distribution pattern in latitude, anti-U-shaped patterns in longitude and with altitude ascending. (2) the dynamics of vegetation coverage can be divided into two periods according to the result of MK mutation test (the breakthrough increasing period around 2005) and the trend of NDVI change: the slow increasing period with an increasing rate of 0.25%/a from 1986 to 2004 (R20.74), and the rapid increasing period with an increasing rate of 0.30%/a from 2005 to 2019 (R20.92). (3) Soil type, landform, vegetation type, land use type and annual average temperature are the main driving factors of vegetation dynamics in the Qinling-Daba Mountains, while annual precipitation, population density and GDP are the secondary driving factors of vegetation dynamics. The land use type and land management policies in the Qinling-Daba Mountains have a strong impact on vegetation cover change, and the climate warming in recent decades plays more important role than precipitation on the vegetation dynamics. These results are of great significance to comprehensively understand the impact of global climate warming and human activities on the natural environment of the Qinling-Daba Mountains.
Horizontal transfer of probable chicken-pathogenicity chromosomal islands betweenStaphylococcus aureusandStaphylococcus agnetis
Authors: Rhoads Douglas D. , Pummil Jeff , Ekesi Nnamdi S. , Alrubaye Adnan A. K. 
Published: March 2023

AbstractStaphylococcus agnetisis an emerging pathogen in chickens but has been most commonly isolated from sub-clinical mastitis in bovines. Previous whole-genome analyses for known virulence genes failed to identify determinants for the switch from mild ductal infections in cattle to severe infections in poultry. We now report identification of a family of 15 kbp, 17-19 gene mobile genetic elements (MGEs) specific to chicken osteomyelitis and dermatitis isolates ofS. agnetis. These MGEs can be present in multiple copies per genome. The MGE has been vectored on a Staphylococcus phage that separately lysogenized twoS. agnetisosteomyelitis strains. TheS. agnetisgenome from a broiler breeder case of ulcerative dermatitis contains 2 orthologs of this MGE, not associated with a prophage. BLASTn and phylogenetic analyses show that there are closely related intact MGEs found in genomes ofS. aureus. The genome from a 1980s isolate from chickens in Ireland contains 3 copies of this MGE. More recent chicken isolates descended from that genome (Poland 2009, Oklahoma 2010, and Arkansas 2018) contain 2 to 4 related copies. Many of the genes of this MGE can be identified in disparate regions of the genomes of other chicken isolates ofS. aureus.BLAST searches of the NCBI databases detect no similar MGEs outside ofS. aureusandS. agnetis.These MGEs encode no proteins related to those produced byStaphylococcus aureusPathogenicity Islands, which have been associated with the transition ofS. aureusfrom human to chicken hosts. Other than mobilization functions, most of the genes in these new MGEs annotate as hypothetical proteins. The MGEs we describe appear to represent a new family of Chromosomal Islands (CIs) shared amongstS. agnetisandS. aureus.Further work is needed to understand the role of these CIs/MGEs in pathogenesis. Analysis of horizontal transfer of genetic elements between isolates and species of Staphylococci provides clues to evolution of host-pathogen interactions as well as revealing critical determinants for animal welfare and human diseases.