bluuebunny/crossref_metadata_2025 huggingface dataset:
Supporting Self-management Through eHealth - Exploring the Needs, Challenges and Solutions in General Practice: A Qualitative and Participatory Design Study
Authors: Djurtoft Chris , Sørensen Kristine , Odgaard Christian , Hoegh Morten , Rathleff Michael S. , Johansen Simon K.
Published: May 2024

Introduction

Digital transformation and integration of eHealth solutions into chronic pain management faces significant challenges that have not yet been met. To realize the potential of eHealth solutions there is a need to understand the challenges, needs and care processes of eHealth into specific contexts and specific purposes. The objective of this study was to explore challenges, barriers, support needs, and visions experienced by patients and general practitioners (GPs) in the context of an eHealth solution designed for chronic pain management in general practice.

Methods

The study used action-research as a methodological framework. We conducted two future workshops involving eight patients living with chronic pain and seven GPs with clinical experience in managing chronic pain. Through case vignettes and inspiration cards, these workshops stimulated discussions and shared knowledge construction. Data were analysed using reflexive thematic analysis, separated by the groups, and were synthesized via a matrix analysis.

Results

The analysis revealed five content summary themes: Theme 1—patients’ experience of challenges in life with pain; Theme 2—challenges in treating patients with chronic pain; Theme 3—patients’ suggestions for the structure of the eHealth solution; Theme 4—GP’ suggestions for the structure of the eHealth solution; and Theme 5—differences and similarities: Visions for an eHealth solution. The analysis generated several touchpoints and tension within the patient-physician encounter.

Conclusion

In conclusion, these themes provide distinct narratives, offering valuable insights into the design objectives. Our study represents a significant advancement in developing personalized and innovative eHealth solutions for general practice, addressing key clinical challenges.

Perspective

Realizing the potential of eHealth solutions, these findings highlight both contrasting and shared viewpoints on design objectives, providing crucial insight into end-user perspectives for effective pain management. Additionally, the study underscores the importance of supported self-management and clinical communication in understanding each patient’s overall presentation within the healthcare system.
Maternal Western-style diet programs skeletal muscle gene expression in lean adolescent Japanese macaque offspring
Authors: Beck Emily A. , Hetrick Byron , Nassar Luis , Turnbull Douglas W. , Dean Tyler A. , Gannon Maureen , Aagaard Kjersti M. , Wesolowski Stephanie R. , Friedman Jacob E. , Kievit Paul , McCurdy Carrie E.
Published: May 2024

Early-life exposure to maternal obesity or a maternal calorically dense Western-style diet (WSD) is strongly associated with a greater risk of metabolic diseases in offspring, most notably insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). Prior studies in our well-characterized Japanese macaque model demonstrated that offspring of dams fed a WSD, even when weaned onto a control (CTR) diet, had reductions in skeletal muscle mitochondrial metabolism and increased skeletal muscle insulin resistance compared to offspring of dams on CTR diet. In the current study, we employed a nested design to test for differences in gene expression in skeletal muscle from lean 3-year-old adolescent offspring from dams fed a maternal WSD in both the presence and absence of maternal obesity or lean dams fed a CTR diet. We included offspring weaned to both a WSD or CTR diet to further account for differences in response to post-weaning diet and interaction effects between diets. Overall, we found that a maternal WSD fed to dams during pregnancy and lactation was the principal driver of differential gene expression (DEG) in offspring muscle at this time point. We identified key gene pathways important in insulin signaling including PI3K-Akt and MAP-kinase, regulation of muscle regeneration, and transcription-translation feedback loops, in both male and female offspring. Muscle DEG showed no measurable difference between offspring of obese dams on WSD compared to those of lean dams fed WSD. A post-weaning WSD effected offspring transcription only in individuals from the maternal CTR diet group but not in maternal WSD group. Collectively, we identify that maternal diet composition has a significant and lasting impact on offspring muscle transcriptome and influences later transcriptional response to WSD in muscle, which may underlie the increased metabolic disease risk in offspring.
TRAPT: A multi-stage fused deep learning framework for transcriptional regulators prediction via integrating large-scale epigenomic data
Authors: Zhang Guorui , Song Chao , Yin Mingxue , Liu Liyuan , Zhang Yuexin , Li Ye , Zhang Jianing , Guo Maozu , Li Chunquan
Published: May 2024

It is a challenging task to identify functional transcriptional regulators, which control expression of gene sets via regulatory elements and epigenomic signals, involving context-specific studies such as development and diseases. Integrating large-scale multi-omics epigenomic data enables the elucidation of the complex epigenomic control patterns of regulatory elements and regulators. Here, we propose TRAPT, a multi-modality deep learning framework that predicts functional transcriptional regulators from a queried gene set by integrating large-scale multi-omics epigenomic data, including histone modifications, ATAC-seq and TR-ChIP-seq. We design two-stage self-knowledge distillation model to learn nonlinear embedded representation of upstream and downstream regulatory element activity, and merge multi-modality epigenomic features from TR and the queried gene sets for inferring regulator activity. Experimental results on 1072 TR-related datasets demonstrate that TRAPT outperforms current state-of-the-art methods in predicting transcriptional regulators, especially in the prediction of transcription co-factors and chromatin regulators. Additionally, we have successfully identified key transcriptional regulators associated with the disease, genetic variation, cell fate decisions, and tissues. Our method provides an innovative perspective for integrating epigenomic data and has the potential to significantly assist researchers in deepening their understanding of gene expression regulation mechanisms.
The impact of ancestral, environmental and genetic influences on germlinede novomutation rates and spectra
Authors: Garcia-Salinas O. Isaac , Hwang Seongwon , Huang Qin Qin , Kaplanis Joanna , Neville Matthew D.C. , Sanghvi Rashesh , Day Felix , Rahbari Raheleh , Scally Aylwyn , Martin Hilary C.
Published: May 2024

De novogermline mutation is an important factor in the evolution of allelic diversity and disease predisposition in a population. Here, we study the influence of genetically-inferred ancestry and environmental factors onde novomutation rates and spectra. Using a genetically diverse sample of ∼10K whole-genome sequenced trios, one of the largestde novomutation catalogues to date, we found that genetically-inferred ancestry is associated with modest but significant changes in both germline mutation rate and spectra across continental populations. These effects may be due to genetic or environmental factors correlated with ancestry. We find epidemiological evidence that exposure to tobacco smoke is significantly associated with increasedde novomutation rate, but it does not mediate the observed ancestry effects. Investigation of several other potential mutagenic factors using Mendelian randomisation showed no consistent effects, except for age of menopause, where increased age corresponded to a reduction inde novomutation rate. Overall, our study presents evidence on new factors influencingde novomutational rate and spectra.
Scalable Screening of Ternary-Code DNA Methylation Dynamics Associated with Human Traits
Authors: Goldberg David C , Cloud Cameron , Lee Sol Moe , Barnes Bret , Gruber Steven , Kim Elliot , Pottekat Anita , Westphal Maximillian S , McAuliffe Luana , Majounie Elisa , KalayilManian Manesh , Zhu Qingdi , Tran Christine , Hansen Mark , Stojakovic Jelena , Parker Jared B , Kohli Rahul M , Porecha Rishi , Renke Nicole , Zhou Wanding
Published: May 2024

Epigenome-wide association studies (EWAS) are transforming our understanding of the interplay between epigenetics and complex human traits and phenotypes. We introduce the Methylation Screening Array (MSA), a new iteration of the Infinium technology for scalable and quantitative screening of trait associations of nuanced ternary-code cytosine modifications in larger, more inclusive, and stratified human populations. MSA integrates EWAS, single-cell, and cell-type-resolved methylome profiles, covering diverse human traits and diseases. Our first MSA applications yield multiple biological insights: we revealed a previously unappreciated role of 5-hydroxymethylcytosine (5hmC) in trait associations and epigenetic clocks. We demonstrated that 5hmCs complement 5-methylcytosines (5mCs) in defining tissues and cells’ epigenetic identities. In-depth analyses highlighted the cell type context of EWAS and GWAS hits. Using this platform, we conducted a comprehensive human 5hmC aging EWAS, discovering tissue-invariant and tissue-specific aging dynamics, including distinct tissue-specific rates of mitotic hyper- and hypomethylation rates. These findings chart a landscape of the complex interplay of the two forms of cytosine modifications in diverse human tissues and their roles in health and disease.
Effects of land use change and elevation on endemic shrub frogs in a biodiversity hotspot
Authors: Lad Himanshu , Gosavi Ninad , Jithin Vijayan , Naniwadekar Rohit
Published: May 2024

Agroforestry, often promoted as a sustainable agriculture practice, is rapidly expanding, often at the cost of primary tropical forests. While agroforestry impacts amphibian diversity negatively, its effects on population demography, microhabitat use and body condition are relatively understudied. This information is crucial for determining and promoting amphibian-friendly land use practices. We compared habitats, population densities, microhabitat use, and body condition of two endemic species of shrub frogs (Pseudophilautus amboliandRaorchestes bombayensis) across 1) elevations (low- and high-elevation forests) and 2) land use categories (cashew, rubber, and low-elevation forests) in the northern part of the Western Ghats Biodiversity Hotspot. Using distance sampling, we demonstrated that abundances of the two shrub frog species differed across elevation categories, withPseudophilautusmore common in low-elevation forests andRaorchestesmore prevalent in high-elevation forests. Both species of frogs exhibited extremely skewed, male-biased sex ratios, with three females for 100 males.Pseudophilautushad lower densities and poor recruitment and exhibited altered microhabitat use in cashew plantations compared to low-elevation forests. Although adult malePseudophilautusdensities in rubber were similar to those in low-elevation forests, they exhibited altered microhabitat use and smaller body sizes than in forests, indicating poor body condition. We demonstrate differential impacts of agroforestry types on shrub frogs. We also demonstrate that distance sampling can be a useful tool for population monitoring of shrub frogs, which comprise almost 25% of the anuran diversity in the Western Ghats. Additionally, there is a need to identify the drivers of extremely skewed sex ratios, which make these species vulnerable to population crashes. Considering the recent downlisting of the two focal species to Least Concern, we advocate for their uplisting to at least Near Threatened status in light of their patchy distribution, negative impacts of rapidly expanding agroforestry plantations and extremely skewed sex ratios.
Ancient genomics reveals a genetic continuum with dual structure in the Classic Copan
Authors: Murray Madeleine , Nakamura Seiichi , Fuentes Melvin , Ogawa Masahiro , Cassidy Lara M. , Gakuhari Takashi , Nakagome Shigeki
Published: May 2024

Copan was a major capital at the southeasternmost of the Maya civilization, serving as a crossroads connecting Central and South America. In 426/427 CE, the city witnessed the establishment of a royal dynasty, which endured for approximately 400 years. Despite extensive historical and archaeological records, there remains limited information regarding the genetic origins of people who resided in Copan. Here, we present seven Classic Copan genomes including an enigmatic dynastic ruler and his sacrificed companion. Our analysis identifies a high genetic affinity of the Classic Copan with present-day Maya. Both groups exhibit an admixture of Mesoamerican and South American Farmer (SAF) ancestry, with a shift in a dominant component from SAF to Mesoamerican. At the individual level, commoners show a more prominent SAF ancestry, while the royal individual demonstrates nearly equal contributions from two ancestors. These results highlight a dual ancestral structure in this geographic extreme of the Classic Maya state, uncovering a cline of Mesoamerican ancestry across individuals.
Proteomic analysis to classify extracellular vesicles and plasmodesmata in Arabidopsis cell culture supernatants
Authors: Takei Takahito , Asou Teppei , Hamakawa Nobuteru , Tanaka Sho , Noguchi Ryo , Sumiyoshi Kohei , Sueyoshi Kenji , Imami Koshi , Hamada Takahiro
Published: May 2024

The plant apoplast contains diverse proteins. In this study, we analyzed the extracellular vesicle proteome using cell culture supernatants. Unexpectedly, many plasmodesmata proteins were identified in the extracellular vesicle fraction. The comparison between the cell culture EV proteome and the plasmodesmata proteome revealed that EV and plasmodesmata proteins were indistinguishable. Highly sensitive imaging analyses showed that PDLP3-GFP, a representative plasmodesmata marker, was localized to plasmodesmata, but it was also present as small granules in apoplast regions. Next, we attempted to distinguish EV proteins from plasmodesmata proteins. The step-wise density gradient ultracentrifugation and clustering analysis separated EV protein clusters (represented by tetraspanins and membrane trafficking proteins) from plasmodesmata clusters (represented by PDLPs and PDCBs). These results provide the basis for future explorations of plant plasmodesmata and EVs.
Linking single-cell transcriptomes with secretion using secretion-encoded single-cell sequencing (SEC-seq)
Authors: Langerman Justin , Baghdasarian Sevana , Cheng Rene Yu-Hong , James Richard G. , Plath Kathrin , Carlo Dino Di
Published: May 2024

Cells secrete numerous proteins and other biomolecules into their surroundings to achieve critical functions – from communicating with other cells to blocking the activity of pathogens. Secretion of cytokines, growth factors, extracellular vesicles, and even recombinant biologic drugs defines the therapeutic potency of many cell therapies. However, gene expression states that drive specific secretory phenotypes are largely unknown. We provide a protocol that enables linking the Secretion amount of a target protein EnCoded (SEC) by thousands of single cells with transcriptional sequencing (seq). SEC-seq leverages microscale hydrogel particles called Nanovials to isolate cells and capture their secretions in close proximity, oligonucleotide-labeled antibodies to tag secretions on Nanovials, and flow cytometry and single-cell RNA-sequencing platforms for readout. Cells on Nanovials can be sorted based on viability, secretion amount, or other surface markers without fixation or permeabilization, and cell and secretion-containing Nanovials are directly introduced into microfluidic droplets-in-oil emulsions for single-cell barcoding of cell transcriptomes and secretions. We have used SEC-seq to link T-cell receptor sequences to the relative amount of associated cytokine secretions, surface marker gene expression with a highly secreting and potential regenerative population of mesenchymal stromal cells, and the transcriptome with high immunoglobulin secretion from plasma cells. Nanovial modification and cell loading takes under 4 hours, and once the desired incubation time is over, staining, cell sorting, and emulsion generation for scRNA-seq can also be completed in under 4 hours. By linking gene expression and secretory strength, SEC-seq can expand our understanding of cell secretion, how it is regulated, and how it can be engineered to make better therapies.
Two operational modes of atomic force microscopy reveal similar mechanical properties for homologous regions of dystrophin and utrophin
Authors: Hua Cailong , Slick Rebecca A. , Vavra Joseph , Muretta Joseph M. , Ervasti James M. , Salapaka Murti V.
Published: May 2024

Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by the absence of the protein dystrophin. Dystrophin is hypothesized to work as a molecular shock absorber that limits myofiber membrane damage when undergoing reversible unfolding upon muscle stretching and contraction. Utrophin is a dystrophin homologue that is under investigation as a protein replacement therapy for DMD. However, it remains uncertain whether utrophin can mechanically substitute for dystrophin. Here, we compared the mechanical properties of homologous utrophin and dystrophin fragments encoding the N terminus through spectrin repeat 3 (UtrN-R3, DysN-R3) using two operational modes of atomic force microscopy (AFM), constant speed and constant force. Our comprehensive data, including the statistics of force magnitude at which the folded domains unfold in constant speed mode and the time of unfolding statistics in constant force mode, show consistent results. We recover parameters of the energy landscape of the domains and conducted Monte Carlo simulations which corroborate the conclusions drawn from experimental data. Our results confirm that UtrN-R3 expressed in bacteria exhibits significantly lower mechanical stiffness compared to insect UtrN-R3, while the mechanical stiffness of the homologous region of dystrophin (DysN-R3) is intermediate between bacterial and insect UtrN-R3, showing greater similarity to bacterial UtrN-R3.

Significance

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by mutations in DMD gene encoding dystrophin. Utrophin, a fetal homologue of dystrophin, is under active investigation as a dystrophin replacement therapy for DMD. However, it is still unknown if it can substitute dystrophin mechanically. Here, we report mechanical properties of both utrophin and dystrophin fragments encoding the N terminus through spectrin repeat 3 (UtrN-R3, DysN-R3) using atomic force microscope (AFM) through two operational modes, constant speed and constant force. Our data, consistent across both modes, confirm that UtrN-R3 expressed in bacteria exhibits significantly lower mechanical stiffness than insect UtrN-R3. Additionally, bacterial DysN-R3 lies between bacterial and insect UtrN-R3 in terms of mechanical properties, leaning closer to bacterial UtrN-R3.
RoCK and ROI: Single-cell transcriptomics with multiplexed enrichment of selected transcripts and region-specific sequencing
Authors: Moro Giulia , Mallona Izaskun , Maillard Joël , Brügger Michael David , Fazilaty Hassan , Szabo Quentin , Valenta Tomas , Handler Kristina , Kerlin Fiona , Moor Andreas E. , Zinzen Robert , Robinson Mark D. , Brunner Erich , Basler Konrad
Published: May 2024

Various tools have been developed to reliably identify, trace and analyze single cells in complex tissues. In recent years, these technologies have been combined with transcriptomic profiling approaches to explore molecular mechanisms that drive development, health, and disease. However, current methods still fall short of profiling single cell transcriptomes comprehensively, with one major challenge being high non-detection rates of specific transcripts and transcript regions. Such information is often crucial to understanding the biology of cells or tissues and includes lowly expressed transcripts, sequence variations and exon junctions. Here, we developed a scRNAseq workflow, RoCK and ROI (Robust Capture of Key transcripts and Regions Of Interest), that tackles these limitations. RoCKseq uses targeted capture to enrich for key transcripts, thereby supporting the detection and identification of cell types and complex phenotypes in scRNAseq experiments. ROIseq directs a subset of reads to a specific region of interest via selective priming to ensure detection. Importantly, RoCK and ROI guarantees efficient retrieval of specific sequence information without compromising overall single cell transcriptome information and our workflow is supported by a novel bioinformatics pipeline to analyze the multimodal information. RoCK and ROI represents a significant enhancement over non-targeted single cell sequencing, particularly when cell categorization depends on transcripts that are missed in standard scRNAseq experiments. In addition, it also allows exploration of biological questions that require assessment of specific sequence elements along the targets to be addressed.
History of recurrent short and long-term coral bleaching events in Indian coral reefs: a systematic review of contrasting bleaching patterns, lessons learned, and future directions
Authors: Thangadurai Thinesh , De Kalyan , Murugesan Sobana , Sivagurunathan P , Peter Riana , Ramasamy Pasiyappazham , Selvin Joseph , Jose Polpass Arul , Bellantuono Anthony
Published: May 2024

Climate change has intensified coral bleaching events, leading to widespread coral mortality and threatening the coral reef survival worldwide. However, species susceptibility patterns to bleaching differ spatially and temporally, making it crucial to understand bleaching impact and species susceptibility patterns across latitudinal ranges, particularly from understudied locations. We critically reviewed 23 years of bleaching episodes on Indian coral reefs (four major reefs and other patch reefs) reported from 1998 to 2020 to understand the geographical footprint of bleaching patterns, species susceptibility differences, and their impact. We found that all four major Indian reef systems (Gulf of Kachchh, Gulf of Mannar, Lakshadweep, and the Andaman Islands) have experienced three major bleaching episodes (1998, 2010, and 2016) and multiple short-term bleaching events. Short-term bleaching events (DHWs> four weeks) created differences in species susceptibility, but the disparity among species diminished to long-term bleaching events (DHWs <4 weeks) in all reef sites.Acropora,Porites,Pocillopora,Montipora,andTurninariain the Gulf of Mannar,Porites,andFaviain the Gulf of Kachchh, andAcroporain the Andaman and Lakshadweep were the most vulnerable genera during all the bleaching events. In terms of recovery,Poritesand other massive forms recovered better than branching forms. Furthermore, species susceptibility pattern analysis (winners vs. losers) to 2016 long-term bleaching events found conflicting results from studies (one-time surveys) in the same area. This result indicates that a one-time survey (survey timing) influences results as bleaching events lengthen, necessitating repeated surveys to determine winners and losers. Although inconsistent data from different study sites makes it difficult to create predictive models, data collected over the past 23 years provides critical insight into coral community susceptibility patterns and bleaching impacts, underscoring the need for systematic, uniform surveys in the future.
Maladaptation in cereal crop landraces following a soot-producing climate catastrophe
Authors: McLaughlin Chloee M. , Shi Yuning , Viswanathan Vishnu , Sawers Ruairidh , Kemanian Armen R. , Lasky Jesse R.
Published: May 2024

Aerosol-producing global catastrophes such as nuclear war, super-volcano eruption, or asteroid strike, although rare, pose a serious threat to human survival. Light-absorbing aerosols would sharply reduce temperature and solar radiation reaching the earth’s surface, decreasing crop productivity including for locally adapted traditional crop varieties, i.e. landraces. Here, we test post-catastrophic climate impacts on barley, maize, rice, and sorghum, four crops with extensive landrace cultivation, under a range of nuclear war scenarios that differ in the amount of black carbon aerosol (soot) injected into the climate model. We used a crop growth model to estimate gradients of environmental stressors that drive local adaptation. We then fit genotype environment associations using high density genomic markers with gradient forest offset (GF offset) methods and predicted maladaptation through time. As a validation, we found that our GF models successfully predicted local adaptation of maize landraces in multiple common gardens across Mexico. We found strong concordance between GF offset and disruptions in climate, and landraces of all tested crop species were predicted to be the most maladapted across space and time where soot-induced climate change was the greatest. We further used our GF models to identify landrace varieties best matched to specific post-catastrophic conditions, indicating potential substitutions for agricultural resilience. We found the best landrace genotype was often far away or in another nation, though countries with more climatic diversity had better within-country substitutions. Our results highlight that a soot-producing catastrophe would result in the global maladaptation of landraces and suggest that current landrace adaptive diversity is insufficient for agricultural resilience in the case of the soot scenarios with the greatest change to climate.
Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state
Authors: Xiang Chuanxi , Raghunathan VijayKrishna , Qiu Yubin , Mehta Manisha , Grosskreutz Cynthia L. , Wilson Christopher W. , Prasanna Ganesh
Published: May 2024

Neurodegeneration in glaucoma patients is clinically identified through longitudinal assessment of structure-function changes, including intraocular pressure, cup-to-disc ratios from fundus images, and optical coherence tomography imaging of the retinal nerve fiber layer. Use of human post-mortem ocular tissue for basic research is rising in the glaucoma field, yet there are challenges in assessing disease stage and severity, since tissue donations with informed consent are often unaccompanied by detailed pre-mortem clinical information. Further, the interpretation of disease severity based solely on anatomical and morphological assessments by histology can be affected by differences in death-to-preservation time and tissue processing. These are difficult confounders that cannot be easily controlled. As pathogenesis and molecular mechanisms can vary depending on the stage and severity of glaucoma, there is a need for the field to maximize use of donated tissue to better understand the molecular mechanisms of glaucoma and develop new therapeutic hypotheses. Further, there is a lack of consensus around the molecular RNA and protein markers that can be used to classify glaucoma severity. Here, we describe a multiparametric grading system that combines structural measurements of the retinal nerve fiber layer with linear regression and principal component analyses of molecular markers of retinal ganglion cells and glia (RBPMS, NEFL, IBA1 and GFAP) to stratify post-mortem glaucoma eyes by the severity of disease. Our findings show that a quantitative grading approach can stratify post-mortem glaucoma samples with minimal clinical histories into at least three severity groups and suggest that this type of approach may be useful for researchers aiming to maximize insights derived from eye bank donor tissue.
Harmonising distributed tree inventory datasets across India can fill critical gaps in tropical ecology
Authors: Anujan Krishna , Mohanbabu Neha , Gopal Abhishek , Surendra Akshay , Krishnan Aparna , Jayanth Ankitha , Nair Tanaya , Ongole Shasank , Sankaran Mahesh
Published: May 2024

Abstract

Global analyses of tree diversity and function are strongly biased geographically, with poor representation from forests of the Indian subcontinent. Even though data from India - representing two-thirds of the subcontinent and spanning a wide range of tree-based biomes - exists, a barrier to syntheses is the absence of accessible and standardised data. Further, with increasing human footprint across ecosystems, data from Indian landscapes, with their long history of human-nature interactions is a key link to understand the future of tropical forested landscapes. Given the long history of human-nature interactions and high human footprint in the region, accessible and standardized data from the subcontinent can enable understanding the future of tropical landscapes under increasing human footprints globally.

Combining literature searches with manual data retrieval, we assembled the INdia Tree Inventory dataset, INvenTree. INvenTree is the largest meta-dataset of peer-reviewed publications (n = 465) from 1991-2023 on geolocated plot-based tree inventories of multispecies communities from Indian ecosystems, in aggregate covering 4653.64 ha and all of its woody biomes.

Using INvenTree, we show extensive sampling across tropical moist and dry forests, the dominant ecosystem types in the country. However, most studies have low sampling effort (median sampled area = 2 ha) and data across studies is not openly accessible (73.33 % of studies representing 83.43% of the sampled area), potentially hindering inclusion into regional or global syntheses.

Significantly, we show majority authorship from within the country; 82.8% of corresponding authors were from India and 73.33% of the studies had all authors affiliated with Indian institutions. We also identify ecological and conservation sampling priority regions based on forest cover and forest loss and set a blueprint for future sampling efforts in the country.

Based on extensive Indian scholarship in forest ecology showcased through the INvenTree dataset, we see opportunity for regional collaboration to create scientific inferences that are larger and scalable, while prioritising data and knowledge equity. Harmonising these existing datasets, and synthesising historic and grey literature, will contribute enormously to understanding the human dimension of tropical ecology as well as informing regional management and conservation.
Telomere-to-Telomere Phased Genome Assembly Using HERRO-Corrected Simplex Nanopore Reads
Authors: Stanojevic Dominik , Lin Dehui , Nurk Sergey , Florez De Sessions Paola , Sikic Mile
Published: May 2024

Telomere-to-telomere phased assemblies have become the norm in genomics. To achieve these for diploid and even polyploid genomes, the contemporary approach involves a combination of two long-read sequencing technologies: high-accuracy long reads, e.g. Pacific Biosciences (PacBio) HiFi or Oxford Nanopore (ONT) 'Duplex' reads, and ultra-long ONT 'Simplex' reads. Using two different technologies increases the cost and the required amount of genomic DNA. Here, we show that comparable results are possible using error correction of ultra-long ONT Simplex reads and then assembling them using state-of-the-art de novo assembly methods. To achieve this, we have developed the deep learning-based HERRO framework, which corrects ONT Simplex reads while carefully preserving differences in related genomic sequences. Taking into account informative positions that differentiate the haplotypes or genomic repeat copies, HERRO achieves an increase of read accuracy of up to 100-fold for diploid human genomes. By combining HERRO with Verkko assembler, we achieve high contiguity on several human genomes by reconstructing many chromosomes telomere-to-telomere, including chromosomes X and Y. HERRO supports both R9.4.1 and R10.4.1 ONT Simplex reads and generalizes well to other species. These results provide an opportunity to reduce the cost of genome sequencing and use corrected ONT reads to analyze more complex genomes with different levels of ploidy or even aneuploidy.
CoNECo: A Corpus for Named Entity recognition and normalization of protein Complexes
Authors: Nastou Katerina , Koutrouli Mikaela , Pyysalo Sampo , Jensen Lars Juhl
Published: May 2024

Motivation

Despite significant progress in biomedical information extraction, there is a lack of resources for Named Entity Recognition (NER) and Normalization (NEN) of protein-containing complexes. Current resources inadequately address the recognition of protein-containing complex names across different organisms, underscoring the crucial need for a dedicated corpus.

Results

We introduce the Complex Named Entity Corpus (CoNECo), an annotated corpus for NER and NEN of complexes. CoNECo comprises 1,621 documents with 2,052 entities, 1,976 of which are normalized to Gene Ontology. We divided the corpus into training, development, and test sets and trained both a transformer-based and dictionary-based tagger on them. Evaluation on the test set demonstrated robust performance, with F1-scores of 73.7% and 61.2%, respectively. Subsequently, we applied the best taggers for comprehensive tagging of the entire openly accessible biomedical literature.

Availability

All resources, including the annotated corpus, training data, and code, are available to the community through Zenodohttps://zenodo.org/records/11263147and GitHubhttps://zenodo.org/records/10693653.
epiTCR-KDA: Knowledge Distillation model on Dihedral Angles for TCR-peptide prediction
Authors: Pham My-Diem Nguyen , Su Chinh Tran-To , Nguyen Thanh-Nhan , Nguyen Hoai-Nghia , Nguyen Dinh Duy An , Giang Hoa , Nguyen Dinh-Thuc , Phan Minh-Duy , Nguyen Vy
Published: May 2024

Motivation: Antigen recognition by T-cell receptors (TCRs) triggers cascades of immune responses. Successful predictions of the TCR and antigen (as peptide) bindings therefore signify the advancements in immunotherapy. However, most of current TCR-peptide interaction predictors fail to predict unseen data. This limitation may be derived from the conventional usage of TCR and/or peptide sequences as input, which may not adequately reflect their structural characteristics. Therefore, incorporating the TCR and peptide structural information into the prediction model to improve the generalizability is necessary. Results: We presented epiTCR-KDA as a new predictor of TCR-peptide binding that utilises structural information, specifically the dihedral angles between the residues of both the peptide and the TCR. This structural descriptor was integrated into a model constructed using knowledge distillation to enhance its generalizability. The epiTCR-KDA demonstrated competitive prediction performance, with an AUC of 0.99 for seen data and AUC of 0.86 for unseen data. Across multiple public datasets, epiTCR-KDA consistently outperformed other predictors, such as epiTCR, NetTCR, BERTrand, TEIM-Seq, TEINet, and ImRex, maintaining a median AUC of 0.9 (ranging from 0.82 to 0.91). Further analysis of epiTCR-KDA performance indicated that the cosine similarity of the dihedral angle vectors between the unseen testing data and training data is crucial for its stable performance. In conclusion, our epiTCR-KDA model, with its capacity to predict for unseen data, has brought us one step closer toward the development of a highly effective pipeline for affordable antigen-based immunotherapy. Availability and implementation: epiTCR-KDA is available on GitHub (https://github.com/ddiem-ri-4D/epiTCR-KDA) .
Gene2role: a role-based gene embedding method for comparative analysis of signed gene regulatory networks
Authors: Zeng Xin , Liu Shu , Liu Bowen , Zhang Weihang , Xu Wanzhe , Toriumi Fujio , Nakai Kenta
Published: May 2024

Motivation

Understanding the dynamics of gene regulatory networks (GRNs) across various cellular states is crucial for deciphering the underlying mechanisms governing cell behavior and functionality. However, current comparative analytical methods, which often focus on simple topological information such as the degree of genes, are limited in their ability to fully capture the similarities and differences among the complex GRNs.

Results

We present Gene2role, a gene embedding approach that leverages multi-hop topological information from genes within signed GRNs. Initially, we demonstrated the effectiveness of Gene2role in capturing the intricate topological nuances of genes using GRNs inferred from four distinct data sources. Then, applying Gene2role to integrated GRNs allowed us to identify genes with significant topological changes across cell types or states, offering a fresh perspective beyond traditional differential gene expression analysis. Additionally, we quantified the stability of gene modules between two cellular states by measuring the changes in the gene embeddings within these modules. In conclusion, our method augments the existing toolkit for probing the dynamic regulatory landscape, thereby opening new avenues for understanding gene behavior and interaction patterns across cellular transitions.
Soil organic carbon stocks and stabilization mechanisms in tidal marshes along estuarine gradients
Authors: Neiske Friederike , Seedtke Maria , Eschenbach Annette , Wilson Monica , Jensen Kai , Becker Joscha N.
Published: May 2024

Tidal marshes store large amounts of soil organic carbon (SOC), however, little is known on SOC stabilization mechanisms in these ecosystems. In estuarine marshes, SOC storage is dominated by a complex interaction of tidal inundation and salinity with biotic ecosystem components, leading to strong spatio-temporal variations within estuaries. Our aim was to assess (i) SOC stocks, (ii) SOC stabilization mechanisms (aggregation and mineral-association), and (iii) their environmental drivers along estuarine gradients. We analyzed SOC stocks and SOC density fractions in topsoil (0-10 cm) and subsoil (10-30 cm) of three marsh zones representing three flooding regimes (daily, monthly, yearly) in three marsh types along the salinity gradient (salt, brackish, freshwater) of the Elbe Estuary, Germany.

Increasing salinity and flooding reduced SOC stocks 0-30 cm (9.3-74.6 t ha-1), which was related to decreasing plant biomass and soil texture. Mineral-associated organic matter (CMAOM) was the largest SOC fraction (59% of total SOC), followed by aggregate-occluded organic matter (CoPOM) (24%) and free particulate organic matter (CfPOM) (16%). The CMAOMamount in topsoils decreased downstream with increasing salinity, reflecting decreasing fine-texture along the estuary. The amount of CoPOMwas higher in topsoils and high marshes, indicating negative effects of flooding on aggregation. The relative proportion of CfPOM(% of total SOC) increased with increasing flooding frequency and reducing soil conditions.

Our results underline the importance of estuarine gradients as drivers of SOC storage and stabilization. Climate-change induced sea-level rise and variations in salinity might reduce SOC storage and stabilization in estuaries.
Overexpression of α-SNAPRhg1can improverhg1-amediated soybean resistance to soybean cyst nematode
Authors: Haarith Deepak , Das Soumita , Nelson Emma , Zaptocony Ryan , Bent Andrew
Published: May 2024

(i)

Therhg1-aandrhg1-bhaplotypes of the soybeanRhg1locus are economically effective tools for the control of soybean cyst nematode (SCN;Heterodera glycines), but ongoing SCN evolution requires improved sources of resistance. BothRhg1haplotypes carry multiple tandem repeat copies of a four-gene block encoding four disparate proteins; resistance efficacy scales with copy number. The haplotypes encode different variants of an unusual α-SNAP protein whose abundance increases in the nematode-reprogrammed plant cells that form the syncytium (nematode feeding site), which subsequently collapses. Simultaneous presence of the two α-SNAPRhg1protein types, or substantially elevated expression of either type, was hypothesized to improve SCN resistance but has not been achievable by conventional plant breeding methods. We accomplished both, by transgenic additions to anrhg1-a Rhg4soybean line. Existing resistance to HG type 0 and HG type 2.5.7 SCN was strengthened, but resistance was not improved against an HG type 1.3.6.7 SCN population that was already highly virulent on the parent line. No significant yield penalties from constitutive overexpression of transgenic α-SNAP genes were observed in greenhouse or initial field studies. Cisgenic combination or elevated expression of the different α-SNAP genes may extend the efficacy and/or durability ofRhg1-mediated resistance. We also observed differential protein abundances for some α-SNAPRhg1isoforms after inoculation with different HG type populations of SCN. These approaches provide opportunities to understand the different mechanisms of the twoRhg1haplotypes and to possibly fine-tune them for better management of SCN.
Hippocampal neuroinflammation causes sex-specific disruptions in action selection, food approach memories, and neuronal activation
Authors: Ganesan Kiruthika , Ghorbanpour Sahar , Kendall William , Broome Sarah Thomas , Gladding Joanne M. , Dhungana Amolika , Abiero Arvie Rodriguez , Mahmoudi Maedeh , Castorina Alessandro , Kendig Michael D. , Becchi Serena , Valova Veronika , Cole Louise , Bradfield Laura A.
Published: May 2024

Hippocampal neuroinflammation is present in multiple diseases and disorders that impact motivated behaviour in a sex-specific manner, but whether neuroinflammation alone is sufficient to disrupt such behaviour is unknown. We investigated this question here using mice. First, the application of an endotoxin to primary cultures containing only hippocampal neurons did not affect their activation. However, when the same endotoxin was applied to mixed neuronal/glial cultures it did increase neuronal activation, providing initial indications of how it might be able to effect behavioural change. We next demonstrated neuroinflammatory effects on behaviour directly, demonstrating that intra-hippocampal administration of the same endotoxin increased locomotor activity and accelerated goal-directed learning in both male and female mice. In contrast, hippocampal neuroinflammation caused sex-specific disruptions to the acquisition of instrumental actions and to Pavlovian food-approach memories. Finally, we showed that hippocampal neuroinflammation had a sexually dimorphic effect on neuronal activation: increasing it in females and decreasing it in males.
Cell-Driven Fluid Dynamics: A Physical Model of Active Systemic Circulation
Authors: Wu Yufei , Benson Morgan A. , Sun Sean X.
Published: May 2024

Active fluid circulation and transport are key functions of living organisms, which drive efficient delivery of oxygen and nutrients to various physiological compartments. Because fluid circulation occurs in a network, the systemic flux and pressure are not simple outcomes of any given component. Rather, they are emergent properties of network elements and network topology. Moreover, consistent pressure and osmolarity gradients across compartments such as the kidney, interstitium, and vessels are known. How these gradients and network properties are established and maintained is an unanswered question in systems physiology. Previous studies have shown that epithelial cells are fluid pumps that actively generate pressure and osmolarity gradients. Polarization and activity of ion exchangers that drive fluid flux in epithelial cells are affected by pressure and osmolarity gradients. Therefore, there is an unexplored coupling between the pressure and osmolarity in the circulating network. Here we develop a mathematical theory that integrates the influence of pressure and osmolarity on solute transport and explores both cell fluid transport and systemic circulation. This model naturally generates pressure and osmolarity gradients across physiological compartments, and demonstrates how systemic transport properties can depend on cell properties, and how the cell state can depend on systemic properties. When epithelial and en-dothelial pumps are considered together, we predict how pressures at various points in the network depend on the overall osmolarity of the system. The model can be improved by including physiological geometries and expanding solute species, and highlights the interplay of fluid properties with cell function in living organisms.
Production and functional verification of 8-gene (GGTA1, CMAH, β4GalNT2, hCD46, hCD55, hCD59, hTBM, hCD39)-edited donor pigs for xenotransplantation
Authors: Wang Jiaoxiang , Xu Kaixiang , Liu Tao , Zhao Heng , Jamal Muhammad Ameen , Chen Gen , Huo Xiaoying , Yang Chang , Jiao Deling , Wei Taiyun , Huang Hanfei , Zhao Hongfang , Guo Jianxiong , Wang Fengchong , Zhang Xiong , Liu Kai , Qu Siming , Wang Gang , Zhao Hong-Ye , Zeng Zhong , Wei Hong-Jiang
Published: May 2024

Gene-edited pig-to-human xenotransplantation continues to make breakthroughs and is expected to enter clinic to solve the global shortage of donor organs. However, which gene combination is suitable for which organ transplantation remains unclear. In this study, we utilized CRISPR/Cas9 gene editing technology, PiggyBac transposon system and somatic cell cloning to construct GTKO/CMAHKO/β4GalNT2KO/hCD46/hCD55/hCD59/hCD39/hTBM 8 gene-edited cloned (GEC) donor pigs, and performed pig to non-human primate (NHP) transplantation to evaluate the effectiveness of these GEC pigs. The multiple vectors were co-transfected into fetal fibroblasts of Diannan miniature pig with O blood type, and 25 colonies were screened out, and one of them carried GGTA1, CMAH and β4GalNT2 biallelic knockout and integration of hCD46, hCD55, hCD59, hTBM and hCD39 genes, which was used as a donor cell for cloning, and a 33-day-old viable fetus was obtained. The fetus was identified and confirmed for normal karyotype and the absence of three xenogeneic antigens α-Gal, Neu5Gc and Sda, and expression of hCD46, hCD55, hCD59, hTBM and hCD39 genes, then the recloning was carried out and 28 cloned piglets were obtained by natural delivery. Molecular identification at DNA, mRNA and protein levels showed that 8 gene editing (GE) was successful in these GEC piglets. Moreover, antigen-antibody binding assay and complement-dependent cytotoxicity assay demonstrated that 8GE effectively reduced the immune incompatibility and kidney xenograft survived up to 15 and 17 days into two NHPs, respectively. During this period, the recipient serum antibodies IgA and IgM, complements C3 and C4, coagulation indicators PT, APTT, TT and FIB, as well as most electrolytes and liver function indicators remained relatively stable. The 24-hour urine output and serum creatinine remained normal at a period of post-transplantation. These results indicated that the 8GEC pigs effectively alleviated immune rejection and exerted life-supporting kidney function in the recipient.