bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocean carbon export can be predicted from ocean color-based phytoplankton communities
Authors: Kramer Sasha J. , Jones Erin L. , Estapa Margaret L. , Paul Nicola L. , Rynearson Tatiana A. , Santoro Alyson E. , Sudek Sebastian , Durkin Colleen A. 
Published: September 2024

AbstractCarbon flux to the deep sea can be dictated by surface ocean phytoplankton community composition, but translating surface ocean observations into quantitative predictions of carbon export requires additional consideration of the underlying ecosystem drivers. Here, we used genetic tracers of phytoplankton detected in surface seawater and within sinking particles collected in the mesopelagic ocean to identify mechanistic links between surface communities and carbon export in the North Pacific and North Atlantic Oceans. Phytoplankton 18S rRNA sequences were sampled over a one-month period in surface seawater and within bulk-collected and individually-isolated sinking particles using mesopelagic sediment traps (100-500m). Nearly all phytoplankton amplicon sequence variants (ASVs) exported from the surface were packaged in large (>300 µm) particles. Individually, these particles contained only a few distinct phytoplankton ASVs, but collectively, large particles transported about half of the surface taxonomic diversity into the mesopelagic. The relative sequence abundances of the surface community detected within particles were quantitatively related to measured POC fluxes: a linear model based on the relative sequence abundance of just two pigment-based phytoplankton taxa, diatoms and photosynthetic Hacrobia, was predictive of POC flux magnitude. These two taxa were also enriched within the ecologically-distinct particle classes that had the greatest influence on carbon export magnitude. As global, hyperspectral ocean color satellites begin to quantify these taxonomic groups in the surface ocean, the relationship of these taxa to carbon fluxes demonstrated here may help generate more accurate global estimates of export.
Dietary specialization drives adaptation, convergence, and integration across the cranial and appendicular skeleton in Waterfowl (Anseriformes)
Authors: Chatterji Ray , Heath Tracy A. , James Helen F. , Hofman Courtney , Sorenson Michael D. , Buckner Janet C. 
Published: September 2024

ABSTRACTConvergence provides strong evidence for adaptive evolution as it reflects shared adaptive responses to the same selection pressures. The waterfowl (order Anseriformes) are an ideal group in which to study convergent evolution as they have repeatedly evolved morphotypes putatively correlated with diet (i.e., dabbler, grazer, diver). Here, we construct the most robust evolutionary hypothesis to date for waterfowl and reveal widespread morphological convergence across the order. We quantified the shape of the skull and hindlimb elements (femur, tibiotarsus, and tarsometatarsus) of 118 species of extant waterfowl using geometric morphometrics. Multivariate generalized evolutionary models provide strong support for a relationship between dietary ecology and skull shape, and evidence for convergent evolution across lineages that share dietary niches. Foraging behavior better explained the evolution of hindlimb shape, but diet still contributed significantly. We also find preliminary evidence for integration across all three measured hindlimb elements with each other and with the skull. We demonstrate that dietary ecology drives morphological convergence within waterfowl, that this convergent evolution involves multiple integrated skeletal structures, and that morphological changes are associated with shifts in the rate of phenotypic evolution.
AlphaMut: a deep reinforcement learning model to suggest helix-disrupting mutations
Authors: Bhargav Prathith , Mukherjee Arnab 
Published: September 2024

1AbstractHelices are important secondary structural motifs within proteins and are pivotal in numerous physiological processes. While amino acids (AA) such as alanine and leucine are known to promote helix formation, proline and glycine disfavor it. Helical structure formation, however, also depends on its environment, and hence, prior prediction of a mutational effect on a helical structure is difficult. Here, we employ a reinforcement learning algorithm to develop a predictive model for helix-disrupting mutations. We start with a toy model consisting of helices with only 30 AA and train different models. Our results show that only a few mutations lead to a drastic disruption of the target helix. We further extend our approach to helices in proteins and validate the results using rigorous free energy calculations. Our strategy identifies amino acids crucial for maintaining structural integrity and predicts key mutations that could alter protein function. Through our work, we present a new use case for reinforcement learning in protein structure disruption.
Mechanical regulation of cuboidal-to-squamous epithelial transition in theDrosophiladeveloping wing
Authors: Harmansa Stefan , Lecuit Thomas 
Published: September 2024

SummaryGrowing tissues are constantly exposed to mechanical stresses that lead to deformations at the cell and tissue scale. In epithelial organs, cells form monolayers whose thickness can change dramatically during development. Here, we address how cell shape changes in the peripodial epithelium of theDrosophilawing disc emerge from the interplay of basement membrane properties with tissue-extrinsic mechanical stress. We show that tissue-extrinsic stress arising from disc proper bending elastically deforms central peripodial cells and induces a cuboidal-to-squamous epithelial transition. In contrast, a rigid basement membrane shields peripheral hinge cells from this bending stress and causes a cuboidal-to-columnar transition. These inverse shape transitions are further amplified by selective shearing of central cells due to coupling via the apical extracellular matrix protein Dumpy. These findings point to a pivotal role of the basement membrane and inter-tissue coupling in the emergence of stress patterns and cell deformations during organ growth.
What does AlphaFold3 learn about antigen and nanobody docking, and what remains unsolved?
Authors: Hitawala Fatima N. , Gray Jeffrey J. 
Published: September 2024

AbstractAntibody therapeutic development is a major focus in healthcare. To accelerate drug development, significant efforts have been directed towards thein silicodesign and screening of antibodies for which high modeling accuracy is necessary. To probe AlphaFold3’s (AF3) capabilities and limitations, we tested AF3’s ability to capture the fine details and interplay between antibody structure prediction and antigen docking accuracy. With one seed, AF3 achieves an 11.0% and 11.4% high-accuracy docking success rate for antibodies and nanobodies, respectively, and a median unbound CDR H3 RMSD accuracy of 2.73 Å and 2.30 Å. CDR H3 accuracy boosts complex prediction accuracy, with antigen context improving CDR H3 accuracy, particularly for loops longer than 15 residues. Combining I-pLDDT with ΔGBimproves discriminative power for correctly docked complexes. However, AF3’s 60% failure rate for antibody and nanobody docking (with single seed sampling) demonstrates necessary refinement to improve antibody design endeavors.
Explore the mechanism of Zigui Yichong Formula in reducing the apoptosis of ovarian granulosa cells in premature ovarian insufficiency based on network pharmacology, molecular docking and cell experiments
Authors: Zhang Xin-Miao , Xi Hong-Yan , Gao Tian-Yu , Liu Shu-Peng , Li Rong-Xia 
Published: September 2024

AbstractObjectiveThis research is conducted with the objective of exploring the underlying mechanism by which the Zigui Yichong Formula (ZGYCF) diminishes granulosa cell apoptosis in the context of premature ovarian insufficiency (POI), utilizing network pharmacology, molecular docking, and cellular experimentation approaches.MethodsThe active constituents and potential therapeutic targets of the 12 medicinal herbs in ZGYCF, which include Rehmannia glutinosa, Cervus nippon, Cornus officinalis, Ligustrum lucidum, Lycium barbarum, Paeonia lactiflora, Astragalus membranaceus, Codonopsis pilosula, Atractylodes macrocephala, Angelica sinensis, Cyperus rotundus, and Glycyrrhiza uralensis, were identified through searches in the TCMSP, BATMAN, HERB, and ETCM databases. Targets associated with the POI condition were gathered from the OpenTargets, DrugBank, and GeneCards databases. Subsequently, a Venn diagram illustrating the compound-target-disease interaction was generated to derive a set of common targets that bridge the gap between pharmacological and pathological targets. A drug-component-target-disease network diagram was created using Cytoscape 3.9.1. Additionally, protein-protein interaction (PPI) networks were built utilizing the STRING database and visualized with Cytoscape to pinpoint key targets within the overlapping target set. Functional annotation and pathway enrichment analyses, including GO and KEGG pathway analyses, were performed using the clusterProfiler package in R 4.2.1 to investigate the underlying mechanisms by which the drug may influence the disease state. The molecular docking of pivotal active constituents with central targets was carried out using AutoDock Tools. Following this, in vitro studies were executed to corroborate the anticipated mechanisms of action of ZGYCF on POI that were inferred from the network pharmacology analysis.ResultsThe selected active components include quercetin, kaempferol, andβ-sitosterol. The core targets identified are Tp53, Bcl-2, and Caspase-3. GO functional and KEGG enrichment analyses indicate that these core targets are primarily enriched in the p53 signaling pathway. Molecular docking results show that quercetin, kaempferol, andβ-sitosterol have good binding affinity with TP53, Bcl-2, and Caspase-3. Additionally, in vitro experiments demonstrate that ZGYCF medicated serum can reduce ACR-induced apoptosis in KGN cells, increase Bcl-2 expression, and decrease the expression of p53, Bax, Caspase-3, and the Bcl-2/Bax ratio.ConclusionZGYCF exerts therapeutic effects on POI through multiple targets and pathways, and it may reduce ACR-induced apoptosis in KGN cells by modulating the p53 signaling pathway.Graphical abstract
From spots to cells: Cell segmentation in spatial transcriptomics with BOMS
Authors: Kamboj Ocima , Park Jeongbin , Stegle Oliver , Hamprecht Fred A. 
Published: September 2024

AbstractImaging-based Spatial Transcriptomics methods enable the study of gene expression and regulation in complex tissues at subcellular resolution. However, inaccurate cell segmentation procedures lead to misassignment of mRNAs to individual cells which can introduce errors in downstream analysis. Current methods estimate cell boundaries using auxiliary DAPI/Poly(A) stains. These stains can be difficult to segment, thus requiring manual tuning of the method, and not all mRNA molecules may be assigned to the correct cells. We describe a new method, based on mean shift, that segments the cells based on the spatial locations and the gene labels of the mRNA spots without requiring any auxiliary images. We evaluate the performance of BOMS across various publicly available datasets and demonstrate that it achieves comparable results to the best existing method while being simple to implement and significantly faster in execution. Open-source code is available athttps://github.com/sciai-lab/boms.
The conversion of forests to agricultural land reduced the content of soil black carbon fractions in a karst rocky desertification area of Southwest China
Authors: Zhang Denan , Teng Qiumei , Huang Kechao , Shen Yuyi , Sun Yingjie , Lyu Shihong , Xu Guangping , Zhang Yanzhao 
Published: September 2024

AbstractUnderstanding the effects of land use on soil black carbon (BC) is critical for correctly interpreting the role of BC in the carbon cycle of karst areas. This study investigated the distribution characteristics of organic carbon (OC), BC, char, and soot and soil physicochemical properties of the soil profiles (0–40 cm) of secondary forest, shrub, farmland, and wasteland in a rocky desertification area of Guangxi Province, a typical karst rocky desertification area in Southwest China. We used a combination of soot/char and δ13CBCisotope analysis to identify the source of BC of these soils. The average value of soil BC was the highest in secondary forest, followed by shrub, farmland, and wasteland in the 0–40 cm soil layer. BC had a positive correlation with OC, char, soot,soil nitrogen, phosphorus and potassium, showed a negative correlation with bulk density. In the black carbon component, char occupies a greater proportion than soot, with the heavy fraction OC exhibiting a higher concentration of BC than the light fraction OC. Conclusively, the BC content was mainly due to C3 plant burning, vehicle exhaust emissions, and fossil fuel utilization.Vegetation restoration improved the soil BC content associated with OC sequestration in the typical karst rocky desertification mountainous area of Southwest Guangxi.
Perceived stress exacerbates psoriasis in human skinin vivo: Insights from a humanized psoriasis mouse model
Authors: Zeltzer Assaf A , Keren Aviad , Shinnawi Samieh , Bertolini Marta , Paus Ralf , Gilhar Amos 
Published: September 2024

AbstractIntroductionThe widely held belief that psychoemotional stress triggers or exacerbates psoriatic skin lesions lacks sufficient scientific evidence. This study investigated this concept using a psoriasis humanized mouse model.MethodsHealthy human skin was grafted onto SCID/beige mice (n=25), and one month later, psoriatic lesions were induced by intradermal injection of autologous, in vitro IL-2- preactivated PBMCs. Following lesion development, topical dexamethasone (DEX) was applied to induce lesion remission. After lesions disappeared, the mice were exposed to either sonic or sham stress for 24 hours.ResultsSonic stress led to the relapse of psoriatic lesions in all human skin xenografts within 14 days. This relapse was associated with significant changes in psoriasis-related skin characteristics: increased epidermal thickness, K16 expression, keratinocyte proliferation, antimicrobial peptide expression (S100A7, hβ2-defensin), and immune activation markers (HLA-DR, ICAM-1, CD1d, MICA-NKG2D). Additionally, epidermal and dermal immune cells (CD3+, CD8+, CD11c+, CD56+, ILC3, c-KIT+ or tryptase+ cells) and psoriasis-associated pro-inflammatory mediators (CXCL10, IL-22, IL-15, IL-17A/F, IFN-γ, and TNFα) were found to be increased. Neurogenic inflammation biomarkers (NGF, NK1-R, and substance P) were also significantly upregulated in stressed mice. Treatment with the FDA-approved neurokinin-1 receptor antagonist, aprepitant, prevented stress-induced psoriatic relapses in 4 out of 5 mice and normalized most inflammatory and neurobiological markers.ConclusionsThese findings provide novel, conclusive evidence that perceived stress can trigger psoriatic lesions in human skin xenografts in vivo and highlight the role of substance P-dependent neurogenic inflammation in this process.
Tumor-induced endothelial RhoA activation mediates tumor cell transendothelial migration and metastasis
Authors: Sajib Md Sanaullah , Zahra Fatema Tuz , Lamprou Margarita , Akwii Racheal Grace , Park Jee Hyun , Osorio Manuel , Tullar Paul , Doci Colleen L. , Zhang Chonghe , Huveneers Stephan , Van Buul Jaap D. , Wang Ming-Hai , Markiewski Maciej M. , Srivastava Sanjay K. , Zheng Yi , Gutkind J. Silvio , Hu Junhao , Bickel Ulrich , Maeda Dean Y. , Zebala John A. , Lionakis Michail S. , Trasti Scott , Mikelis Constantinos M. 
Published: September 2024

Abstract/SummaryThe endothelial barrier plays an active role in transendothelial tumor cell migration during metastasis, however, the endothelial regulatory elements of this step remain obscure. Here we show that endothelial RhoA activation is a determining factor during this process. Breast tumor cell-induced endothelial RhoA activation is the combined outcome of paracrine IL-8-dependent and cell-to-cell contact β1integrin-mediated mechanisms, with elements of this pathway correlating with clinical data. Endothelial-specific RhoA blockade orin vivodeficiency inhibited the transendothelial migration and metastatic potential of human breast tumor and three murine syngeneic tumor cell lines, similar to the pharmacological blockade of the downstream RhoA pathway. These findings highlight endothelial RhoA as a potent, universal target in the tumor microenvironment for anti-metastatic treatment of solid tumors.
Engineering CD3 Subunits with Endoplasmic Reticulum Retention Signal Facilitates Allogeneic CAR T Cell Production
Authors: Ebrahimiyan Hamidreza , Sayadmanesh Ali , Hesaraki Mahdi , Ebrahimi Marzieh , Baharand Hossein , Basiri Mohsen 
Published: September 2024

AbstractThe success of autologous CAR T cell therapies has driven interest in developing off-the-shelf allogeneic CAR T cells as a scalable and readily available option for broader patient access. Most of the current approaches involve the knockout of T cell receptor (TCR) subunits via genome editing for preventing graft-versus-host disease (GvHD). However, clinical translation of these methods faces challenges due to manufacturing complexities and emerging safety concerns like unintended long deletions and chromosomal loss. In this study, we explored an alternative approach by engineering synthetic CD3 subunits containing an endoplasmic reticulum retention (ERR) signal to suppress TCR surface expression by disrupting its trafficking to the plasma membrane. We screened multiple CD3-ERR candidate designs to identify the construct with the highest efficacy in TCR downregulation. The selected candidate, CD3ζ-ERR, was further characterized, demonstrating its ability to minimize TCR-mediated activation and alloreactivity without affecting T cell phenotype, cell cycle and cytokine-induced expansion. Subsequent assays revealed that CD3ζ-ERR CD19 CAR T cells retained their CAR-mediated cytotoxic function against CD19+malignant cells. This study presents an alternative approach for TCR downregulation that circumvents genome editing. By using a transgene compatible with conventional viral vector delivery, this approach holds promise for scalable clinical-grade manufacturing of allogeneic CAR T cell therapies.Translational Impact StatementOur study introduces a scalable method to engineer allogeneic CAR T cells by reducing TCR expression without genome editing, thereby minimizing the risk of immune rejection (GvHD) while maintaining antitumor efficacy. This approach offers a practical and clinically translatable solution for producing “off-the-shelf” CAR T cell therapies, potentially broadening access to these life-saving treatments and streamlining their integration into existing clinical manufacturing processes.
Peasants at the queen’s table?: The microbiome’s dynamics throughout swarming preparation in honey bees (Apis mellifera)
Authors: Kolasa Michał. R. , Molasy Bartłomiej , Strachecka Aneta , Michalik Anna 
Published: September 2024

AbstractThe intricate relationship between hosts and bacterial symbionts was crucial for the evolution of multiple insect clades. Western honey bees(Apis mellifera)have distinctive and highly stable microbiomes in terms of bacterial taxonomic composition. However, despite the significant development of molecular techniques observed in recent decades, we still are far from understanding much about the dynamics of honey bees’ microbiomes in terms of their strain diversity and quantities. The overall stable composition of their microbiome and complex behavior make honey bees a perfect model species for studying the gut-brain axis, where the gut microbiome can efficiently influence the host’s behavior. Here, by implementing high-throughput amplicon sequencing of bacterial 16S rRNA V4 and V1V2 hypervariable regions alongside a cutting-edge quantification approach, we aimed to describe the dynamic in honey bee young workers’ microbiome composition and quantity throughout swarming preparation.Our results show no changes in microbial absolute abundances throughout the swarming preparation among young worker bees. The V4 and V1V2 datasets congruently reconstructed microbial composition with some notable exceptions, and differential abundance analysis indicated thatBombellaandBartonellasignificantly changed over batches.
STANCE: a unified statistical model to detect cell-type-specific spatially variable genes in spatial transcriptomics
Authors: Su Haohao , Wu Yuesong , Chen Bin , Cui Yuehua 
Published: September 2024

AbstractA significant challenge in analyzing spatial transcriptomics data is the effective and efficient detection of spatially variable genes (SVGs), whose expression exhibits non-random spatial patterns in tissues. Many SVGs show spatial variation in expression that is highly correlated with cell type categories or compositions, leading to the concept of cell type-specific spatially variable genes (ctSVGs). Existing statistical methods for detecting ctSVGs treat cell type-specific spatial effects as fixed effects when modeling, resulting in a critical issue: the testing results are not invariant to the rotation of spatial coordinates. Additionally, an SVG may display random spatial patterns within a cell type, and a ctSVG may exhibit random spatial patterns from a general perspective, indicating that an SVG does not necessarily have to be a ctSVG, and vice versa. This poses challenges in real analysis when detecting SVGs or ctSVGs. To address these problems, we propose STANCE, a unified statistical model developed to detect both SVG and ctSVGs in spatial transcriptomics. By integrating gene expression, spatial location, and cell type composition through a linear mixed-effect model, STANCE enables the identification of both SVGs and ctSVGs in an initial stage, followed by a second stage test dedicated to ctSVG detection. Its design ensures robustness in complex scenarios and the results are spatial rotation invariant. We demonstrated the performance of STANCE through comprehensive simulations and analyses of three public datasets. The downstream analyses based on ctSVGs detected by STANCE suggest promising future applications of the model in spatial transcriptomics and various areas of genome biology. A software implementation of STANCE is available athttps://github.com/Cui-STT-Lab/STANCE.
TMX1, a disulfide oxidoreductase, is necessary for T cell function through regulation of CD3ζ
Authors: Chai Timothy , Loh Kyle M. , Weissman Irving L. 
Published: September 2024

ABSTRACTT cell-targeted therapies are commonly used to manage T cell hyperactivity in autoimmune disorders, graft-versus-host diseases (GVHD), and transplant rejections. However, many patients experience significant side effects or inadequate responses to current treatments, highlighting the urgent need for alternative strategies. In this study, we searched for regulators of T cells through proximity labeling with APEX2 to detect proteins interacting with CD8α, a coreceptor of the T-cell receptor (TCR). This screen revealed TMX1, an ER resident transmembrane disulfide oxidoreductase, is essential for T cell cytotoxicity and NFAT, NFκB, and AP1 signaling but not cell proliferation. TMX1 deletion decreases surface TCR expression and destabilizes CD3ζ, a subunit of TCR complex; however, overexpression of CD3ζ rescues the phenotype, suggesting that TMX1 is not required for CD3ζ function. Mechanistically, TMX1 was found to directly engage the CxxC motif of CD3δ, which has been reported to be essential for proper TCR assembly and function. We hypothesize that the loss of TMX1 interaction with CD3δ leads to impaired TCR assembly and subsequent CD3ζ destabilization. These findings identify TMX1 as a novel regulator of T-cell receptor assembly and a potential target for immunosuppressive therapy.