bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-integrin αvβ6 autoantibodies are a novel predictive biomarker in ulcerative colitis
Authors: Livanos Alexandra E , Dunn Alexandra , Fischer Jeremy , Ungaro Ryan C , Turpin Williams , Lee Sun-Ho , Rui Shumin , Del Valle Diane Marie , Jougon Julia J , Martinez-Delgado Gustavo , Riddle Mark S , Murray Joseph A , Laird Renee M , Torres Joana , Agrawal Manasi , Magee Jared S , Dervieux Thierry , Gnjatic Sacha , Sheppard Dean , Sands Bruce E , Porter Chad K , Croitoru Kenneth , Petralia Francesca ,   CCC-GEM Project Research Consortium,   OSCCAR Consortium, Colombel Jean-Frederic , Mehandru Saurabh 
Published: November 2022

AbstractBackground and AimsBetter biomarkers for prediction of ulcerative colitis (UC) development and prognostication are needed. Anti-integrin αvβ6 autoantibodies (anti-αvβ6) have been described in UC patients. Here, we tested for the presence of anti-αvβ6 antibodies in the pre-clinical phase of UC and studied their association with disease-related outcomes after diagnosis.MethodsAnti-αvβ6 were measured in 4 longitudinal serum samples collected from 82 subjects who later developed UC and 82 matched controls from a Department of Defense pre-clinical cohort (PREDICTS). In a distinct, external validation cohort (GEM), we tested 12 pre-UC subjects and 49 matched controls. Further, anti-αvβ6 were measured in 2 incident UC cohorts (COMPASS n=55 and OSCCAR n=104) and associations between anti-αvβ6 and UC-related outcomes were defined using Cox proportional-hazards model.ResultsAnti-αvβ6 were significantly higher among individuals who developed UC compared to controls up to 10 years before diagnosis in PREDICTS. The anti-αvβ6 seropositivity was 12.2% 10 years before diagnosis and increased to 52.4% at the time of diagnosis in subjects who developed UC compared with 2.7% in controls across the 4 timepoints. Anti-αvβ6 predicted UC development with an AUC of at least 0.8 up to 10 years before diagnosis. The presence of anti-αvβ6 in pre-clinical UC samples was validated in the GEM cohort. Finally, high anti-αvβ6 was associated with a composite of adverse UC-outcomes including hospitalization, disease extension, colectomy, systemic steroid use and/or escalation to biologic therapy in recently diagnosed UC.ConclusionAnti-integrin αvβ6 auto-antibodies precede the clinical diagnosis of UC by up to 10 years and are associated with adverse UC-related outcomes.
Taste adaptations associated with host-specialization in the specialistDrosophila sechellia
Authors: Reisenman Carolina E. , Wong Joshua , Vedagarbha Namrata , Livelo Catherine , Scott Kristin 
Published: November 2022

ABSTRACTChemosensory-driven hostplant specialization is a major force mediating insect ecological adaptation and speciation.Drosophila sechellia, a species endemic to the Seychelles islands, feeds and oviposits onMorinda citrifoliaalmost exclusively. This fruit is harmless toD. sechelliabut toxic to otherDrosophilidae, including the closely related generalistsD. simulansandD. melanogaster, due to its high content of fatty acids. While several olfactory adaptations mediatingD. sechellia’spreference for its host have been uncovered, the role of taste has been much less examined. We found thatD. sechelliahas reduced taste and feeding aversion to bitter compounds and host fatty acids that are aversive toD. melanogasterandD. simulans. The loss of aversion to canavanine, coumarin, and fatty acids arose in theD. sechellialineage, as its sister speciesD. simulansshowed responses akin to those ofD. melanogaster. D. sechelliahas increased taste and feeding responses towardsM. citrifolia. These results are in line withD. sechellia’sloss of genes encoding bitter gustatory receptors (GRs) inD. melanogaster. We found that twoGRgenes which are lost inD. sechellia,GR39a.aandGR28b.a, influence the reduction of aversive responses to some bitter compounds. Also,D. sechelliahas increased appetite for a prominent host fatty acid compound that is toxic to its relatives. Our results support the hypothesis that changes in the taste system, specifically a reduction of sensitivity to bitter compounds that deter generalist ancestors, contribute to the specialization ofD. sechelliafor its host.Summary statementTaste specializations in the specialistDrosophila sechelliainclude a lineage-specific reduced sensitivity to bitter compounds associated with losses of gustatory receptors, and increased appetite for Noni and host fatty acids.
Adaptive nanopore sequencing for single cell characterization of cancer mutations and gene rearrangements
Authors: Grimes Susan M. , Kim Heon Seok , Roy Sharmili , Sathe Anuja , Ayala Carlos I. , Almeda-Notestine Alison F. , Haebe Sarah , Shree Tanaya , Levy Ronald , Lau Billy T. , Ji Hanlee P. 
Published: November 2022

ABSTRACTIn this proof-of-concept study, we developed a single cell method that identifies somatic alterations found in coding regions of mRNAs and integrates these mutation genotypes with their matching cell transcriptomes. We used nanopore adaptive sampling on single cell cDNA libraries, generated long read sequences from target gene transcripts and identified coding variants among individual cells. Short-read single cell transcriptomes characterized the cell types with mutations. We delineated CRISPR edits from a cancer cell line. From primary cancer samples, we targeted hundreds of cancer genes, identified somatic coding mutations and a gene rearrangement among individual tumor cells.
Neighbourhood species richness and drought-tolerance traits modulate tree growth and δ13C responses to drought
Authors: Schnabel Florian , Barry Kathryn E. , Eckhardt Susanne , Guillemot Joannès , Geilmann Heike , Kahl Anja , Moossen Heiko , Bauhus Jürgen , Wirth Christian 
Published: November 2022

AbstractMixed-species forests are promoted as a forest management strategy for climate change adaptation, but whether they are more resistant to drought than monospecific forests remains contested. Particularly, the trait-based mechanisms driving the role of tree diversity under drought remain elusive.Using tree cores from a large-scale biodiversity experiment, we investigated tree growth and physiological stress responses (i.e. increase in wood carbon isotopic ratio; δ13C) to changes in climate-induced water availability (wet to dry years) along gradients in neighbourhood tree species richness and drought-tolerance traits. We hypothesized that neighbourhood species richness increases growth and decreases δ13C and that these relationships are modulated by the abiotic (i.e. climatic conditions) and the biotic context. We characterized the biotic context using drought-tolerance traits of focal trees and their neighbours. These traits are related to cavitation resistance vs resource acquisition and stomatal control.Tree growth increased with neighbourhood species richness. However, we did not observe a universal relief of water stress in species-rich neighbourhoods. Neighbourhood species richness effects on growth and δ13C did not strengthen from wet to dry years. Instead, richness-growth and richness-δ13C relationships were modulated by climatic conditions and the traits of trees and their neighbours. At either end of each drought-tolerance gradient, species responded in opposing directions during drought and non-drought years.We show that species’ drought-tolerance traits can explain the strength and nature of biodiversity-ecosystem functioning relationships in experimental tree communities experiencing drought. Mixing tree species can increase growth but may not universally relieve drought stress.One-sentence summaryThe drought-tolerance traits of trees and their neighbours determine biodiversity-ecosystem functioning relationships in experimental tree communities.
Lidocaine Induces Apoptosis in Head and Neck Squamous Cell Carcinoma Through Activation of Bitter Taste Receptor T2R14
Authors: Miller Zoey A. , Mueller Arielle , Holivert Jennifer F , Ma Ray Z. , Muthuswami Sahil , Park April , McMahon Derek B. , Carey Ryan M. , Lee Robert J. 
Published: November 2022

SUMMARYHead and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs and their activation can induce apoptosis. Lidocaine is a local anesthetic used in various clinical applications which can also activate bitter taste receptor 14 (T2R14). Lidocaine may have some anti-tumor effects in other cancers, but the mechanism has been mysterious. Here, we found that lidocaine causes intracellular Ca2+mobilization through activation of T2R14 in HSNCC cells. T2R14 activation with lidocaine depolarizes the mitochondrial membrane, inhibits cell proliferation, and induces apoptosis. Concomitant mitochondrial Ca2+influx, ROS production causes T2R14-dependent accumulation of poly-ubiquinated proteins, suggesting inhibition of the proteasome as a novel component of T2R14-induced apoptosis. Lidocaine may have therapeutic potential in HNSCC as a topical gel or intratumor injection, warranting future clinical studies.HIGHLIGHTSLidocaine activates bitter taste receptor 14 (T2R14) to increase intracellular Ca2+and decrease cAMP in head and neck squamous cell carcinoma (HSNCC) cellsLidocaine decreases cell viability and cell proliferation, depolarizes the mitochondrial membrane, and causes production of reactive oxygen species (ROS)T2R14 activation with lidocaine induces apoptosis and inhibits the ubiquitin proteasome system (UPS)Lung squamous cell carcinoma (SCC) cells and HNSCC tumor spheroids undergo apoptosis or structural disbandment, respectively, with lidocaine
Binding and sequestration of poison frog alkaloids by a plasma globulin
Authors: Alvarez-Buylla Aurora , Moya-Garzon Maria Dolores , Rangel Alexandra E. , Tapia Elicio E. , Tanzo Julia , Soh H. Tom , Coloma Luis A. , Long Jonathan Z. , O’Connell Lauren A. 
Published: November 2022

ABSTRACTAlkaloids are important bioactive molecules throughout the natural world, and in many animals they serve as a source of chemical defense against predation. Dendrobatid poison frogs bioaccumulate alkaloids from their diet to make themselves toxic or unpalatable to predators. Despite the proposed roles of plasma proteins as mediators of alkaloid trafficking and bioavailability, the responsible proteins have not been identified. We use chemical approaches to show that a ~50 kDa plasma protein is the principal alkaloid binding molecule in blood from poison frogs. Proteomic and biochemical studies establish this plasma protein to be liver-derived alkaloid-binding globulin (ABG) that is a member of the serine-protease inhibitor (serpin) family. In addition to alkaloid binding activity, ABG sequesters and regulates the bioavailability of “free” plasma alkaloidsin vitro. Unexpectedly, ABG is not related to saxiphilin, albumin, or other known vitamin carriers, but instead exhibits sequence and structural homology to mammalian hormone carriers and amphibian biliverdin binding proteins. Alkaloid-binding globulin (ABG) represents a new small molecule binding functionality in serpin proteins, a novel mechanism of plasma alkaloid transport in poison frogs, and more broadly points towards serpins acting as tunable scaffolds for small molecule binding and transport across different organisms.
Optimization-Based Decoding of Imaging Spatial Transcriptomics Data
Authors: Bryan John P. , Binan Loïc , McCann Cai , Eldar Yonina C. , Farhi Samouil L. , Cleary Brian 
Published: November 2022

MotivationImaging Spatial Transcriptomics (iST) techniques characterize gene expression in cells in their native context by imaging barcoded probes for mRNA with single molecule resolution. However, the need to acquire many rounds of high-magnification imaging data limits the throughput and impact of existing methods.ResultsWe describe the Joint Sparse method for Imaging Transcriptomics (JSIT), an algorithm for decoding lower magnification IT data than that used in standard experimental workflows. JSIT incorporates codebook knowledge and sparsity assumptions into an optimization problem which is less reliant on well separated optical signals than current pipelines. Using experimental data obtained by performing Multiplexed Error-Robust Fluorescence in situ Hybridization (MERFISH) on tissue from mouse motor cortex, we demonstrate that JSIT enables improved throughput and recovery performance over standard decoding methods.Contactyonina.eldar@weizmann.ac.il,sfarhi@broadinstitute.org,bcleary@bu.eduAvailability and ImplementationSoftware implementation of JSIT, together with example files, are available athttps://github.com/jpbryan13/JSIT.Supplementary InformationSupplementary data are available atBioinformaticsonline.
A Sexual Bias in mitochondrial protein-coding gene expression across different tissues and the prognostic value in multiple cancers
Authors: Tardin da Silva Alan , dos Santos Ferreira Cristina , Medina-Acosta Enrique 
Published: November 2022

ABSTRACTMitochondria in mammalian cells provide ATP through oxidative phosphorylation. The overproduction of reactive oxygen species (ROS) in mitochondrial cells promotes cancer by modifying gene expression or function. Mating introduces competing mitochondrial (mtDNA) and nuclear DNA (nDNA) gene products, leading to biological differences between males and females for diseases and disorders such as cancer. There is a significant sex bias in aging-related conditions. We aimed to investigate whether sex and age affect mitochondrial protein-coding gene expression in cancer and, if so, to determine the prognosis value in survival outcomes, stemness, and immune cell infiltrates. We compared normal versus primary tumor transcriptomes (bulk RNA-Seq) from The Cancer Genome Atlas (TCGA), and the Genotype-Tissue Expression (GTEx) projects to test these hypotheses. Correlations between gene expression, survival, protective or risk factor, stemness, and immune cell infiltrate were performed in RStudio using UCSC Xena Shiny. Eleven mitochondrial protein-coding genes were altered in brain cancer (MT-ND2,MT-ND1,MT-ATP8,MT-ATP6,MT-CO2,MT-CYB,MT-CO3,MT-ND4L,MT-ND4,MT-ND3,MT-CO1). MT-ND5 and MT-ND6 are disproportionately expressed in female brain tissues. Mitochondrial global polymorphic expression sites of variation were more significant in the 50-59 and 60-79-year-old age groups than in the 20-49-year-old age groups. Pan-cancer survival analysis revealed a 4-component gene signature (MT-CO1,MT-CO2,MT-ND5,and MT-ND6) downregulated in low-grade glioma (LGG). This gene signature increased LGG overall survival, disease-specific survival, and progression-free interval without sex-specific association. However, the correlation with disease-free interval survival was female-specific. The 4-component gene signature was protective in LGG but risky in thymoma cancer and uterine corpus endometrial carcinoma. In LGG, the 4-component gene signature positively correlated with immune monocyte, NK, and B cell infiltrates and negatively correlated with T cell CD4+ Th2, macrophage M1 and M2, myeloid dendritic cell, and neutrophil. We identified a 13-component mitochondrial protein-coding gene signature associated with stemness in kidney chromophobe. A sex-biased effect was observed in mitochondrial protein-coding for brain tissues, with a female bias. However, an aging effect with higher polymorphic site expression was observed in male tissues. We conclude that the differentially expressed mitochondrial protein-coding genes provide new insights into carcinogenesis, helping to identify new prognostic markers. The overexpression of the 4-component gene signature is associated with a better prognosis in LGG, with positive and negative correlations with immune cell infiltrates.
Rapid Real-time Squiggle Classification for Read Until Using RawMap
Authors: Sadasivan Harisankar , Wadden Jack , Goliya Kush , Ranjan Piyush , Dickson Robert P. , Blaauw David , Das Reetuparna , Narayanasamy Satish 
Published: November 2022

AbstractReadUntil enables Oxford Nanopore Technology’s (ONT) sequencers to selectively sequence reads of target species in real-time. This enables efficient microbial enrichment for applications such as microbial abundance estimation and is particularly beneficial for metagenomic samples with a very high fraction of non-target reads (>99% can be human reads). However, read-until requires a fast and accurate software filter that analyzes a short prefix of a read and determines if it belongs to a microbe of interest (target) or not. The baseline Read Until pipeline uses a deep neural network-based basecaller called Guppy and is slow and inaccurate for this task (∼60% of bases sequenced are unclassified).We present RawMap, an efficient CPU-only microbial species-agnostic Read Until classifier for filtering non-target human reads in the squiggle space. RawMap uses a Support Vector Machine (SVM), which is trained to distinguish human from microbe using non-linear and non-stationary characteristics of ONT’s squiggle output (continuous electrical signals). Compared to the baseline Read Until pipeline, RawMap is a 1327X faster classifier and significantly improves the sequencing time and cost, and compute time savings. We show that RawMap augmented pipelines reduce sequencing time and cost by ∼24% and computing cost by ∼22%. Additionally, since RawMap is agnostic to microbial species, it can also classify microbial species it is not trained on.We also discuss how RawMap may be used as an alternative to the RT-PCR test for viral load quantification of SARS-CoV-2.Availability and implementationSoftware is released with MIT License and available on GitHub:https://github.com/harisankarsadasivan/RawMap
Region- and variance-based DNA methylation analyses reveal novel disease genes and pathways for systemic lupus erythematosus
Authors: Guo Mengbiao , Wang Ting-You , Shen Jiangshan Jane , Wang Yong-Fei , Lau Yu-Lung , Yang Wanling 
Published: November 2022

AbstractBackgroundSystemic lupus erythematosus (SLE) is a prototype autoimmune disease with unclear pathogenesis. DNA methylation is an important regulatory mechanism on gene expression, providing a key angle to understand disease mechanisms. To understand the pathways involved in SLE, and to develop biomarkers for its diagnosis and treatment, we analyzed DNA methylation profiles on blood cells from SLE patients and healthy controls.ResultsWe identified most differentially methylated regions (DMRs) in T cells, while majority of differentially variable sites (DVSs) were found in B cells, featuring hypervariability in enhancers. We observed a prominent T cell receptor (TCR) signaling cluster with consistent hypermethylation and a B cell receptor (BCR) cluster with highly increased variability in SLE. Genes involved in innate immunity were often found hypomethylated, while adaptive immunity genes were featured with hypermethylation. Using a machine learning approach, we identified 60 genes that accurately distinguished SLE patients from healthy individuals, which also showed correlation with disease activities.ConclusionsThis study highlights the role of lymphocyte receptor aberrations in the disease and identified a list of genes showing great potential as biomarkers and shedding new light on disease mechanisms, through novel analyses of methylation data.
1000 years of population, warfare, and climate change in pre-Columbian societies of the Central Andes
Authors: Lima Mauricio , Gayó Eugenia M. , Gurruchaga Andone , Estay Sergio A. , Santoro Calogero M. 
Published: November 2022

AbstractDifferent Andean societies underwent processes of expansion and collapse during propitious or adverse climate conditions, resource boost or depletion along with population variations. Previous studies have emphasized that demographic collapses of polities in the Central Andes Area were triggered by warfare and the negative impacts of fluctuating climate (droughts) on crop productivity. Nevertheless, the interactions between climatic variability, demography and warfare have been less thoroughly evaluated. We develop population dynamic models to test feedback relationships between population growth, climate change and warfare in the Central Andes, where considerable regional hydroclimate variations have occurred over a millennium. Through population models, we found out that the rise and demise of social polities in the northern coast of the Central Andes appear to be a consequence of climate change. In contrast, for the highlands of Peru and the Titicaca basin, population models suggest that warfare intensity has a negative effect on population growth rates.
Fake IDs? Widespread misannotation of DNA Transposons as a General Transcription Factor
Authors: Hassan Nozhat T. , Adelson David L. 
Published: November 2022

AbstractThe annotation of transposable elements (TEs) is a critical part of our understanding of genomes, however, the accuracy of annotation pipelines remains an issue as TEs are frequently underestimated or misannotated. We report the General Transcription Factor II-I Repeat Domain-Containing Protein 2 (GTF2IRD2) was used to erroneously annotate DNA transposons in a variety of non-mammalian species as GTF2IRD2 contains a 3’ fused hAT transposase domain. This study emphasises that the misannotation of TEs astrans-regulatory elements, such as transcription factors, can lead to errors in phylogenetic trees based on orthologs and to significant wasted time for investigators interested in gene regulation and characterising non-mammalian genomes.
The biotoxin BMAA promotes dysfunction via distinct mechanisms in neuroblastoma and glioblastoma cells
Authors: Burton Bryan , Collins Kate , Brooks Jordan , Moore Ellie , Marx Karly , Renner Abigail , Wilcox Kaylei , Osowski Keith , Riley Jordan , Rowe Jarron , Pawlus Matthew 
Published: November 2022

ABSTRACTChronic exposure to the Cyanobacteria biotoxin Beta-methylamino-L-alanine (BMAA) has been associated with development of a sporadic form of ALS called Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC), as observed within certain Indigenous populations of Guam and Japan. Studies in primate models and cell culture have supported the association of BMAA with ALS/PDC, yet the pathological mechanisms at play remain incompletely characterized, effectively stalling the development of rationally-designed therapeutics or application of preventative measures for this disease. In this study we demonstrate for the first time that sub-excitotoxic doses of BMAA modulate the canonical Wnt signaling pathway to drive cellular defects in human neuroblastoma cells, suggesting a potential mechanism by which BMAA may promote neurological disease. Further, we demonstrate here that the effects of BMAA can be reversed in cell culture by use of pharmacological modulators of the Wnt pathway, revealing the potential value of targeting this pathway therapeutically. Interestingly, our results suggest the existence of a distinct Wnt-independent mechanism activated by BMAA in glioblastoma cells, highlighting the likelihood that neurological disease may result from the cumulative effects of distinct cell-type specific mechanisms of BMAA toxicity.