bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating sTNF/TNFR1 activation on VGluT2+ spinal cord interneurons improves immune function after mid-thoracic spinal cord injury
Authors: Martynyuk Tetyana , Ricard Jerome , Bracchi-Ricard Valerie , Price Samuel , McGrath Jenna , Dougherty Kimberly , Tom Veronica , Bethea John R. 
Published: July 2024

AbstractSpinal cord injury (SCI) is a devastating condition with 250,000 to 500,000 new cases globally each year. Respiratory infections, e.g., pneumonia and influenza are the leading cause of death after SCI. Unfortunately, there is a poor understanding of how altered neuro-immune communication impacts an individual’s outcome to infection. In humans and rodents, SCI leads to maladaptive changes in the spinal-sympathetic reflex (SSR) circuit which is crucial to sympathetic function. The cause of the impaired immune function may be related to harmful neuroinflammation which is detrimental to homeostatic neuronal function, aberrant plasticity, and hyperexcitable circuits. Soluble tumor necrosis factor (sTNF) is a pro-inflammatory cytokine that is elevated in the CNS after SCI and remains elevated for several months after injury. By pharmacologically attenuating sTNF in the CNS after SCI we were able to demonstrate improved immune function. Furthermore, when we investigated the specific cellular population which may be involved in altered neuro-immune communication we reported that excessive TNFR1 activity on excitatory INs promotes immune dysfunction. Furthermore, this observation is NF-kB dependent in VGluT2+ INs. Our data is the first report of a target within the CNS, TNFR1, that contributes to SCI-induced immune dysfunction after T9-SCI and is a potential avenue for future therapeutics.
Cryptic diversity shapes coral symbioses, physiology, and response to thermal challenge
Authors: Aichelman Hannah E. , Benson Brooke E. , Gomez-Campo Kelly , Martinez-Rugerio M. Isabel , Fifer James E. , Tsang Laura , Hughes Annabel M. , Bove Colleen B. , Nieves Olivia C. , Pereslete Alyssa M. , Stanizzi Darren , Kriefall Nicola G. , Baumann Justin H. , Rippe John P. , Gondola Plinio , Castillo Karl D. , Davies Sarah W. 
Published: July 2024

AbstractCoral persistence in the Anthropocene is shaped by interactions among holobiont partners (coral animals, microbial symbionts) and their environment. Cryptic coral lineages–genetically distinct yet morphologically similar groups–are critically important as they often exhibit functional diversity relevant to thermal tolerance. Additionally, environmental parameters such as thermal variability may promote tolerance, but how variability interacts with holobiont partners to shape responses to thermal challenge remains unclear. Here, we identified three cryptic lineages ofSiderastrea sidereain Bocas del Toro, Panamá that differ in distributions across inshore and offshore reefs, microbial associations, holobiont phenomes, and skeleton morphologies. A thermal variability experiment failed to increase thermal tolerance, but subsequent thermal challenge and recovery revealed one lineage maintained elevated energetic reserves, photochemical efficiency, and growth. Lastly, coral cores highlighted that this lineage also exhibited faster growth historically. Functional variation among cryptic lineages highlights their importance in predicting coral reef responses to climate change.TeaserCryptic host diversity drives coral phenotypes relevant to climate change.
Expansion of mammary intraepithelial lymphocytes and intestinal inputs shape T cell dynamics in lactogenesis
Authors: Jaquish Abigail , Phung Eleni , Gong Xutong , Baldominos-Flores Pilar , Galvan-Pena Silvia , Bursulaya Isabelle , Magill Ian ,   ImmgenT consortium, Bertrand Kerri , Chambers Christina , Agudo Judith , Mathis Diane , Benoist Christophe , Ramanan Deepshika 
Published: July 2024

ABSTRACTPregnancy brings about profound changes to the mammary gland in preparation for lactation. Changes in immunocyte populations that accompany this rapid remodeling are incompletely understood. We comprehensively analyzed mammary T cells through all parous stages, revealing a marked increase in CD4+ and CD8+ T effector cells in late pregnancy and lactation. T cell expansion was partly dependent on microbial signals and included an increase in TCRαβ+CD8αα+ cells with strong cytotoxic markers, located in the epithelium, that resemble intraepithelial lymphocytes of mucosal tissues. This relationship was substantiated by demonstrating T cell migration from gut to mammary gland in late pregnancy, by TCR clonotypes shared by intestine and mammary tissue in the same mouse, including intriguing gut TCR families. Putative counterparts of CD8αα+ IELs were found in human milk. Mammary T cells are thus poised to manage the transition from a non-mucosal tissue to a mucosal barrier during lactogenesis.
Sulfonylurea receptor coupled conductances alter the performace of two central pattern generating circuits inCancer borealis
Authors: Kedia Sonal , Awal Naziru M. , Seddon Jackie , Marder Eve 
Published: July 2024

AbstractNeuronal activity and energy supply must maintain a fine balance for neuronal fitness. Various channels of communication between the two could impact network output in different ways. Sulfonylurea receptors (SURs) are a modification of ATP-binding cassette proteins (ABCs) that confer ATP-dependent gating on their associated ion channels. They are widely expressed and link metabolic states directly to neuronal activity. The role they play varies in different circuits, both enabling bursting and inhibiting activity in pathological conditions. The crab, Cancer borealis, has central patterns generators (CPGs) that fire in rhythmic bursts nearly constantly and it is unknown how energy availability influences these networks. The pyloric network of the stomatogastric ganglion (STG) and cardiac ganglion (GC) control rhythmic contractions of the foregut and heart respectively. Pharmacological manipulation of SURs results in opposite effects in the two CPGs. Neuronal firing completely stops in the STG when SUR-associated channels are open, and firing increases when the channels are closed. This results from a decrease in the excitability of pyloric dilator (PD) neurons, which are a part of the pacemaker kernel. The neurons of the CG, paradoxically, increase firing within bursts when SUR-associated channels are opened, and bursting slows when SUR-associated channels are closed. The channel permeability and sensitivities analyses present novel SUR-conductance biophysics, which nevertheless change activity in ways reminiscent of the predominantly studied mammalian receptor/channels. We suggest that SUR-associated conductances allow different neurons to respond to energy states in different ways through a common mechanism.
An updated DNA barcoding tool forAloe veraand related CITES-regulated species
Authors: Woudstra Yannick , Rees Paul , Rakotoarisoa Solofo E. , Rønsted Nina , Howard Caroline , Grace Olwen M. 
Published: July 2024

AbstractDNA barcoding has revolutionised the identification of illegally traded material of endangered species as it overcomes the lack of resolution encountered with morphological identification. Nonetheless, in recently evolved and highly diverse clades, such as the relatives ofAloe vera, the lack of interspecific sequence variation in standardised markers compromises the barcoding efficacy. We present a new DNA barcoding tool using 189 nuclear markers, optimised for aloes (Asphodelaceae, Alooideae). We built a comprehensive sequence reference dataset from taxonomically verified sources for >300 species and validated its reliability for identification using phylogenomic inference. Seven anonymised samples from verified botanical collections and ten plants seized at London Heathrow Airport were correctly identified to species level, including a critically endangered species from Madagascar. Commercially purchased samples were confirmed to be the species as advertised. An accurate, reliable DNA barcoding method for aloe identification introduces new assurance to regulatory processes for endangered plants in trade.
DGTS overproduced in seed plants is excluded from plastid membranes and promotes endomembrane expansion
Authors: Salomon Sarah , Schilling Marion , Albrieux Catherine , Si Larbi Grégory , Jouneau Pierre-Henri , Roy Sylvaine , Falconet Denis , Michaud Morgane , Jouhet Juliette 
Published: July 2024

AbstractPlants and algae must adapt to environmental changes, facing various stresses that negatively impact their growth and development. One common stress is phosphate (Pi) deficiency, which is often in limiting quantity in the environment. In response to Pi deficiency, these organisms increase Pi uptake and remobilize intracellular Pi. Phospholipids are degraded to provide Pi and replaced by non-phosphorous lipids, such as glycolipids or betaine lipids. During the evolution, seed plants lost their capacity to synthesize betaine lipid. By expressing BTA1 genes, involved in the synthesis of diacylglyceryl-N,N,N-trimethyl-homoserine (DGTS), from different species, our work shows that DGTS can be produced in seed plants. In Arabidopsis, expressing BTA1 under a phosphate starvation-inducible promoter resulted in limited DGTS production without having any impact on plant growth or lipid remodeling. In transient expression systems inNicotiana benthamiana, leaves were able to accumulate DGTS up to 20 % of their glycerolipid content at a slight expense of galactolipid and phospholipid production. At the subcellular level, we showed that DGTS is absent from plastid and seems to be enriched in endomembrane, driving an ER membrane proliferation. Finally, DGTS synthesis pathway seems to compete with PC synthesis via the Kennedy pathway but does not seem to be derived from PC diacylglycerol backbone and therefore does not interfere with the eukaryotic pathway involved in galactolipid synthesis.
Climate adaptation inP. trichocarpa: key adaptive loci identified for stomata and leaf traits
Authors: Klein Marie C , Meng Zi , Bailey-Bale Jack , Milner Suzanne , Shi Peicai , Muchero Wellington , Chen Jin-Gui , Tschaplinski Timothy J , Jacobson Daniel , Lagergren John , Lane Matthew , O’Brien Chris , Chhetri Hari , Shu Mengjun , Freer-Smith Peter , Buckley Thomas N. , Magney Troy , Monroe J Grey , Tuskan Gerald A. , Taylor Gail 
Published: July 2024

AbstractIdentifying the genetic basis of traits underlying climate adaptation remains a key goal for predicting species responses to climate change, enabling the elucidation of gene targets for future climate-resilient crops. Here, we measured 14 leaf and stomatal traits under control (well-watered) and drought conditions, subsampling a diversity collection of over 1,300Populus trichocarpagenotypes, a potential biofuel feedstock crop. Stomatal traits were correlated with the climate of origin for genotypes, such that those originating from environments subject to water deficit tended to have smaller stomata, but with higher density. Stomatal traits were also correlated with leaf morphology, with larger leaves having larger stomata and lower stomatal density mirrored in correlations to climate of origin. The direction of plastic responses - reduced stomatal size under drought - mirrors the correlations seen among genotypes with respect to the aridity of environmental origin. Genome-Wide Association Studies (GWAS) identified loci underlying trait diversity, including candidates contributing to stomatal size. We used climate of origin to predict stomatal size in genotypes with unknown trait values and found that these predicted phenotypes confirmed empirically measured allele effects. Finally, we found evidence that future climates may select for alleles contributing to decreased stomatal size, with the strength of selection depending on the availability of moisture. These findings reveal adaptive variation in stomatal and physiological traits along with underlying genetic loci, with implications for future selection and breeding - providing insights into the responses to future climate change.HighlightResearch onPopulus trichocarpareveals adaptation of physiological and stomatal traits linked to drought tolerance, with genotypes from arid regions exhibiting smaller stomata, offering insights for climate change adaptation and sustainable biofuel production.
Nanopore-based native RNA sequencing of human transcriptomes reveals the complexity of mRNA modifications and crosstalk between RNA regulatory features
Authors: Kim Yerin , O’Neill Kieran , Garant Jean-Michel , Saville Luke , Haile Simon , Ghashghaei Maryam , Park Yongjin P. , Jones Steven J.M. , Vu Ly P 
Published: July 2024

AbstractThe identification and functional characterization of chemical modifications on an mRNA molecule, in particular N6-methyladenosine (m6A) modification, significantly broadened our understanding of RNA function and regulation. While interactions between RNA modifications and other RNA features have been proposed, direct evidence showing correlation is limited. Here, using Oxford Nanopore long-read direct RNA sequencing (dRNA-seq), we simultaneously interrogate the transcriptome and epitranscriptome of a human leukemia cell line to investigate the correlation between m6A modifications, mRNA abundance, polyA tail length and alternative splicing. We demonstrated that high quality dRNA-seq is critically important for unbiased and large-scale correlative analyses of these RNA features. The genome wide landscape of RNA methylation was captured with single nucleotide and individual isoform resolution. The length of polyA tails were ascribed to individual transcripts and genes, allowing for unprecedent measurement of polyA tail length distribution. Global analysis indicated negative association between polyA tail length and mRNA abundance while uncovering pathway-specific responses upon depletion of m6A forming enzyme METTL3. Overall, our study presented a rich dRNA-seq data resource which has been validated and can be further exploited to inquire into the complexity of RNA modifications and potential interplays between RNA regulatory elements.
Localizedin vivogene editing of murine cancer-associated fibroblasts
Authors: Kuhn Nicholas F. , Zaleta-Linares Itzia , Nyberg William A. , Eyquem Justin , Krummel Matthew F. 
Published: July 2024

AbstractDiscovering the role of fibroblasts residing in the tumor microenvironment (TME) requires controlled, localized perturbations because fibroblasts play critical roles in regulating immunity and tumor biology at multiple sites. Systemic perturbations can lead to unintended, confounding secondary effects, and methods to locally genetically engineer fibroblasts are lacking. To specifically investigate murine stromal cell perturbations restricted to the TME, we developed an adeno-associated virus (AAV)-based method to target any gene-of-interest in fibroblasts at high efficiency (>80%). As proof of concept, we generated single (sKO) and double gene KOs (dKO) ofOsmr,Tgfbr2, andIl1r1in cancer-associated fibroblasts (CAFs) and investigated how their cell states and those of other cells of the TME subsequently change in mouse models of melanoma and pancreatic ductal adenocarcinoma (PDAC). Furthermore, we developed anin vivoknockin-knockout (KIKO) strategy to achieve long-term tracking of CAFs with target gene KO via knocked-in reporter gene expression. This validatedin vivogene editing toolbox is fast, affordable, and modular, and thus holds great potential for further exploration of gene function in stromal cells residing in tumors and beyond.Graphical Abstract
Re2Pair: Increasing the Scalability of RePair by Decreasing Memory Usage
Authors: Kim Justin , Varki Rahul , Oliva Marco , Boucher Christina 
Published: July 2024

AbstractThe RePair compression algorithm produces a context-free grammar by iteratively substituting the most frequently occurring pair of consecutive symbols with a new symbol until all consecutive pairs of symbols appear only once in the compressed text. It is widely used in the settings of bioinformatics, machine learning, and information retrieval where random access to the original input text is needed. For example, in pangenomics, RePair is used for random access to a population of genomes. BigRePair improves the scalability of the original RePair algorithm by using Prefix-Free Parsing (PFP) to preprocess the text prior to building the RePair grammar. Despite the efficiency of PFP on repetitive text, there is a scalability issue with the size of the parse which causes a memory bottleneck in BigRePair. In this paper, we design and implement recursive RePair (denoted as Re2Pair), which builds the RePair grammar using recursive PFP. Our novel algorithm faces the challenge of constructing the RePair grammar without direct access to the parse of text, relying solely on the dictionary of the text and the parse and dictionary of the parse of the text. We compare Re2Pair to BigRePair using SARS-CoV-2 haplotypes and haplotypes from the 1000 Genomes Project. We show that our method Re2Pair achieves over a 40% peak memory reduction and a speed up ranging between 12% to 79% compared to BigRePair when compressing the largest input texts in all experiments. Re2Pair is made publicly available under the GNU public license here:https://github.com/jkim210/Recursive-RePair2012 ACM Subject ClassificationTheory of computation → Formal languages and automata theory
Filtering for highly variable genes and high quality spots improves phylogenetic analysis of cancer spatial transcriptomics Visium data
Authors: Gavryushkina Alexandra “Sasha” , Pinkney Holly R , Diermeier Sarah D , Gavryushkin Alex 
Published: July 2024

AbstractPhylogenetic relationship of cells within tumours can help us to understand how cancer develops in space and time, iden-tify driver mutations and other evolutionary events that enable can-cer growth and spread. Numerous studies have reconstructed phylo-genies from single-cell DNA-seq data. Here we are looking into the problem of phylogenetic analysis of spatially resolved near single-cell RNA-seq data, which is a cost-efficient alternative (or complemen-tary) data source that integrates multiple sources of evolutionary information including point mutations, copy-number changes, and epimutations. Recent attempts to use such data, although promis-ing, raised many methodological challenges. Here, we explored data-preprocessing and modelling approaches for evolutionary analyses of Visium spatial transcriptomics data. We conclude that using only highly variable genes and accounting for heterogeneous RNA capture across tissue-covered spots improves the reconstructed topological relationships and influences estimated branch lengths.
Unbounding fish: Assessing vulnerability to overexploitation for transboundary fish populations
Authors: Gangal Mayuresh , Arthur Rohan , Suri Venkatachalam , Pandit Awadhesh , Tyagi Abhinav , Prakash Praveen , Sule Mihir , Majgaonkar Iravatee , Krishnaswamy Jagadish , Ramakrishnan Uma 
Published: July 2024

AbstractTropical fish populations often traverse management boundaries, making it difficult to evaluate species vulnerabilities and optimise sustainable fishing goals. Most vulnerability assessments rely on life histories and gear susceptibility, but ignore transboundary differences in management, which can strongly affect vulnerability. We propose a novel vulnerability matrix, the Biology – Transboundary Management (BTM) index for individual fish populations based on 1) Species specific vulnerability 2) distribution of genetically-distinct populations with respect to jurisdictional boundaries and 3) sustainability of management practices across jurisdictions. Combining single-nucleotide polymorphism (SNP) analyses and policy assessments, we evaluate relative vulnerabilities of nine commercially relevant fish populations over a 3400km stretch of India’s west coast, across multiple jurisdictions. The BTM matrix indicates that transboundary differences in management strongly influences biological vulnerability. The matrix is sensitive to population-level differences and policy changes. Our analyses emphasise the need for population-level assessments and transboundary cooperation in achieving sustainable multi species fisheries.
The state-of-the-art machine learning model for Plasma Protein Binding Prediction: computational modeling with OCHEM and experimental validation
Authors: Han Zunsheng , Xia Zhonghua , Xia Jie , Tetko Igor V. , Wu Song 
Published: July 2024

ABSTRACTPlasma protein binding (PPB) is closely related to pharmacokinetics, pharmacodynamics and drug toxicity. Prediction of PPB is an alternative to experimental approaches that are known to be time-consuming and costly. Although there are various models and web servers for PPB prediction already available, they suffer from low prediction accuracy and poor interpretability, in particular for molecules with high values, and are most often not properly validated in prospective studies. Here, we carried out strict data curation, and applied consensus modeling to obtain a model with a coefficient of determination of 0.90 and 0.91 on the training set and the test set, respectively. This model was further validated in a prospective study to predict 63 poly-fluorinated and another 25 highly diverse compounds, and its performance for both these sets was superior to that of other previously reported models. To identify structural features related to PPB, we analyzed a model based on Morgan2 fingerprints and identified that features such as aromatic rings, halogen atoms, heterocyclic rings can discriminate high- and low-PPB molecules. In conclusion, we have established a PPB prediction model that showed state-of-the-art performance in prospective screening, which we have made publicly available in the OCHEM platform (https://ochem.eu/article/29).Graphic Abstract
Influence of predation mortality on past and future dynamics of Pacific Herring: implications for stock status and future biomass
Authors: Doherty Beau , Johnson Samuel D. N. , Benson Ashleen J. , Cox Sean P. , Cleary Jaclyn S. , Lane Jim 
Published: July 2024

AbstractThe recovery of marine mammals from historical over-exploitation in the 1970s represents one of the largest changes in trophic structure in the northeast Pacific Ocean over the last century, for which the impacts on key forage species such as Pacific Herring (Clupea pallasii) are poorly understood. This has prompted hypotheses that increasing marine mammal populations are the primary cause for productivity declines for some fish stocks and their lack of recovery to historical abundance levels. In this study, we evaluate such a hypothesis for Pacific Herring by quantifying historical predation rates by key predators including cetaceans (Pacific Humpbacks, Grey Whales), pinnipeds (Stellar Sea Lions, Harbour Seals), and piscivorous fish (Pacific Hake). Predation mortality is quantified via a novel approach that integrates a single-species catch-at-age model with estimates of predator consumption derived from bioenergetic models. We found that predator consumption, largely driven by Humpback Whales, explained increasing Pacific Herring natural mortality rates in recent years and could be used to forecast future mortality. Incorporating higher future natural mortality rates produced higher estimates of current stock status (1.09-1.2B0) based on lower estimates of equilibrium unfished biomass (17.5-20.3 kt). Conversely, models that assumed mortality was more like the historical average had lower stock status (0.63B0) and higher estimates of unfished biomass (32.4 kt). We demonstrate a practical approach for ecosystem modelling that can be used to develop operating model scenarios for management strategy evaluation, improving scientific defensibility by removing an element of analyst choice for future mortality scenarios. We discuss how simpler modifications to single-species model assumptions can be more pragmatic for providing fisheries management advice, while more complex multi-species or ecosystem models might provide more nuanced insights for exploring research questions related to multi-species ecosystems and fisheries interactions.