bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gelatinous fibers develop asymmetrically for posture support of bends and coils in common bean vine
Authors: Onyenedum Joyce G. , Sousa-Baena Mariane S. , Acevedo Angelique A. , Hunt Lena , Glos Rosemary A.E. , Anderson Charles T. 
Published: May 2024

ABSTRACTGelatinous (G)-fibers are common in the stems of twining vines (twiners), but their role remain unclear given the lack of developmental insights. Here, we characterize the developmental anatomy of G-fiber formation in common bean stems (Phaseolus vulgarisL., Fabaceae). G-fibers in common bean exhibit cell wall organization comparable to other species, consisting of cellulose and Rhamnogalacturonan-I pectins, with possible traces of lignin. We show that G-fibers are absent in the actively circumnutating stems, thus these tensile fibers are not associated with the dynamic searching movements characteristics of twiners. Instead, we found that after a subtle bend or dramatic coil is formed, G-fibers form asymmetrically on the concave side of the stem for posture maintenance. Therefore, G-fibers do not drive movement, but provide support for existing bends, thus stabilizing the helical conformation of twiners around its host to avoid slippage. Finally, we present common bean as an emergent system to study twiners and growth form diversity given its easy cultivation, self-pollination, fast growth, and habit diversity arising from plant breeding, and the ability to induce habit shifts through simple modifications to light conditions.
The vulnerability of overwintering insects to loss of the subnivium
Authors: Thompson Kimberly L. , Pauli Jonathan N. , Zuckerberg Benjamin 
Published: May 2024

AbstractWinter climate change threatens the subnivium (i.e., the microhabitat that exists between the snowpack and the ground), and the community of species that depends on it for overwintering survival. One group of species that will likely exhibit an array of responses to subnivium loss are overwintering insects because they vary in their cold tolerance strategies and lower thermal limits. For an assemblage of eight insect species that range in their cold tolerance strategies and include both pollinators and pests, we investigated species-specific vulnerabilities to shifting subnivium conditions by applying information on each species’ supercooling point to spatially- and temporally-explicit models of minimum subnivium temperatures for three warming scenarios in the Great Lakes region in the United States: current conditions (i.e., control), +3°C, and +5°C. Although species varied in their vulnerabilities, our predictions indicated that exposure to lethal temperatures generally decreased under warming of 3°C, but increased under warming of 5°C, indicating that once enough warming happens, a tipping point is reached. We also found that freeze-tolerant species (i.e., species that can survive at temperatures below their supercooling point) possess a more cryptic vulnerability to winter climate change because sustained below-freezing temperatures were sufficient to induce vulnerability (i.e., predicted mortality), even when temperatures were above the supercooling point. This work provides a better understanding of the vulnerability of different insect species to winter climate change, which is critical because overwintering survival and the fitness consequences incurred during overwintering likely represent important bottlenecks for the population dynamics of subnivium-dependent species.
Evaluating the feasibility of medium chain oleochemical synthesis using microbial chain elongation
Authors: Agena Ethan , Gois Ian M. , Bowers Connor M. , Mahadevan Radhakrishnan , Scarborough Matthew J. , Lawson Christopher E. 
Published: May 2024

AbstractChain elongating bacteria are a unique guild of strictly anaerobic bacteria that have garnered interest for sustainable chemical manufacturing from carbon-rich wet and gaseous waste streams. They produce C6-C8medium-chain fatty acids which are valuable platform chemicals that can be used directly, or derivatized to service a wide range of chemical industries. However, the application of chain elongating bacteria for synthesizing products beyond C6-C8medium-chain fatty acids has not been evaluated. In this study, we assess the feasibility of expanding the product spectrum of chain elongating bacteria to C9-C12fatty acids, along with the synthesis of C6fatty alcohols, dicarboxylic acids, diols, and methyl ketones. We propose several metabolic engineering strategies to accomplish these conversions in chain elongating bacteria and utilize constraint-based metabolic modelling to predict pathway stoichiometries, assess thermodynamic feasibility, and estimate ATP and product yields. We also evaluate how producing alternative products impacts the growth rate of chain elongating bacteria via resource allocation modelling, revealing a trade-off between product carbon length and class versus cell growth rate. Together, these results highlight the potential for using chain elongating bacteria as a platform for diverse oleochemical biomanufacturing and offer a starting point for guiding future metabolic engineering efforts aimed at expanding their product range.Graphical AbstractIn this work, the authors use constraint-based metabolic modelling and enzyme cost minimization to assess the feasibility of using metabolic engineering to expand the product spectrum of anaerobic chain elongating bacteria.One Sentence SummaryIn this work, the authors use constraint-based metabolic modelling and enzyme cost minimization to assess the feasibility of using metabolic engineering to expand the product spectrum of anaerobic chain elongating bacteria.
Machine learning models of human tissue microbiomes for tissue-of-origin prediction
Authors: Mahmoudabadi Gita , Quake Stephen R. 
Published: May 2024

AbstractThere is increasing interest in using microbial data diagnostically for tissue health monitoring such as in early cancer detection. To build such models, we need to understand whether normal tissue microbiomes can also be predictive of tissue of origin, and importantly ask how contaminants may contribute to model performance. In this study, using the Tabula Sapiens Microbiome dataset, we built machine learning models of human tissue microbiomes that can predict tissue of origin. This may in part explain how tumor types can be predicted based on the tumor microbiomes. We also demonstrate that machine learning models built using contaminants alone, though not as powerful as those built on true signal, can still predict tissue of origin. Reassuringly, the addition of contaminants to true signal does not increase the performance over models built on true signal. Overall, our findings raise the burden of proof for predictive models of the human tissue and tumor microbiomes. Without addressing the magnitude of contribution from contaminants to model performance, a model’s reproducibility and its clinical value becomes questionable. We also discuss the optimal microbial taxonomic resolution for building these models.
Predicting locus phylogenetic utility using machine learning
Authors: Knyshov Alexander , Walling Alexandra , Guccione Caitlin , Schwartz Rachel 
Published: May 2024

AbstractDisentangling evolutionary signal from noise in genomic datasets is essential to building phylogenies. The efficiency of current sequencing platforms and workflows has resulted in a plethora of large-scale phylogenomic datasets where, if signal is weak, it can be easily overwhelmed with non-phylogenetic signal and noise. However, the nature of the latter is not well understood. Although certain factors have been investigated and verified as impacting the accuracy of phylogenetic reconstructions, many others (as well as interactions among different factors) remain understudied. Here we use a large simulation-based dataset and machine learning to better understand the factors, and their interactions, that contribute to species tree error. We trained Random Forest regression models on the features extracted from simulated alignments under known phylogenies to predict the phylogenetic utility of the loci. Loci with the worst utility were then filtered out, resulting in an improved signal-to-noise ratio across the dataset. We investigated the relative importance of different features used by the model, as well as how they correspond to the originally simulated properties. We further used the model on several diverse empirical datasets to predict and subset the least reliable loci and re-infer the phylogenies. We measure the impacts of the subsetting on the overall topologies, difficult nodes identified in the original studies, as well as branch length distribution. Our results suggest that subsetting based on the utility predicted by the model can improve the topological accuracy of the trees and their average statistical support, and limits paralogy and its effects. Although the topology generated from the filtered datasets may not always be dramatically different from that generated from unfiltered data, the worst loci consistently yielded different topologies and worst statistical support, indicating that our protocol identified phylogenetic noise in the empirical data.
Protocols for circulating neutrophil depletion in neonatal C57Bl/6 mice
Authors: Mukherjee Devashis , Satyavolu Sriram , Cioffi Sarah , Thomas Asha , Li Yuexin , Nayak Lalitha 
Published: May 2024

ABSTRACTMurine neonatal neutrophil depletion strategies have problems achieving deep neutrophil clearance and accurate residual neutrophil fraction detection. An isotype switch method can achieve profound neutrophil clearance using a combination of anti-Ly6G and anti-rat κ Ig light chain antibodies in adult C57Bl/6 mice, proven by extra- and intracellular Ly6G detection by flow cytometry. We adapted this technique to neonatal mice, testing four neutrophil depletion strategies in the peripheral circulation, bone marrow, and spleen. Four protocols were tested: P3 Ly6G and P1-3 Ly6G (anti-Ly6G on postnatal days (P) 3 and 1-3 respectively), and P3 Dual and P1-3 Dual (anti-Ly6G and anti-rat κ Ig light chain on P3 and P1-3 respectively). Intracellular and extracellular Ly6G presence was detected using flow cytometry. Isotype control antibodies were used as controls. P1-3 Dual protocol achieved significantly better neutrophil depletion than the P1-3 Ly6G or P3 Ly6G protocols (97% vs. 74% and 97% vs. 50%, respectively) in the peripheral circulation. The P3 Dual protocol alone was enough to achieve significantly better neutrophil clearance (93%) than any of the Ly6G alone protocols. The Ly6G alone protocols led to near-total elimination of extracellular Ly6G. However, there was a significant presence of intracellular Ly6G in the CD45+ cell population, evading detection by extracellular Ly6G antibody-based detection methods. P3 protocols perform better than P1-3 protocols for bone marrow and splenic neutrophil clearance. Thus, the P3 Dual protocol might be the most effective and ethical protocol to induce profound neutrophil depletion in neonatal mice, an alternative to daily anti-Ly6G injections.Summary SentenceDual antibody-based neutrophil depletion effectively induces circulating neutrophil clearance in neonatal mice.
Utilizing transcriptomics and metabolomics reveal drought tolerance mechanism inNicotiana tabacum
Authors: Yin Quanyu , Feng Zhao , Ren Zhichao , Wang Hui , Wu Dongling , Jaisi Amit , Yang Mengquan 
Published: May 2024

AbstractThe development and growth of plants are significantly impacted by adverse surroundings, particularly drought conditions. The yield and quality of plants, in particular, are heavily reliant on the presence of favorable growth conditions. Here, we performed comprehensive research to investigate phenotype, physiological characteristics, transcriptomic and metabolomic changes inNicotiana tabacum(N. tabacum) in responses to drought stress (DS). This work aimed to investigate the detailed responses ofN. tabacumto DS under different drought conditions (CK, well-watered; LD, light drought; MD, moderate drought and SD, severe drought).N. tabacumgrew normally under CK but was inhibited under LD, MD and SD stress; the relative water content, transpiration rate and protective enzyme activity significantly influenced under DS. In the LD/CK, MD/CK and SD/CK comparison groups, there were 7483, 15558 and 16876 differentially expressed genes (DEGs), respectively, and 410, 485 and 523 differentially accumulated metabolites (DAMs), respectively. The combined analysis of transcriptomic and metabolomic data unveiled the significant involvement of phenylpropanoid biosynthesis in theN. tabacum’s response to drought stress. These findings characterized the key metabolites and genes in responses to drought stress inN. tabacum, hence offering valuable insights into the underlying mechanisms driving these responses to DS and maintaining plant health under climate change.
Depicting the regulatory role of JZOL on TRP channels in the treatment of Acute Bronchitis based on the combination of clinical trials, computational analysis and in vivo experiments
Authors: Fan Qinhua , Wu Chongming , Du Yawei , Wang Boyang , Xie Yanming , Zhang Zeling , Su Wenquan , Wang Zizhuo , Xu Changchang , Li Xueke , Ding Ying , An Xinjiang , Chen Jing , Xiao Yunying , Yu Rong , Li Nan , Wang Juan , Teng Yiqun , Lv Hongfen , Yang Nian , Wen Yuling , Huang Xiaoli , Pan Wei , Liu Yufeng , Xi Xueqin , Zhao Qianye , Liu Changshan , Xu Jian , Zhang Haitao , Zhuo Lie , Rong Qiangquan , Xia Yu , Shen Qin , Li Shao , Wang Junhong , Wu Shengxian 
Published: May 2024

AbstractThe comparison between traditional Chinese medicine Jinzhen Oral Liquid (JZOL) and western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This head to head randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1 and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels was the key mechanism of action.
Early precursor-derived pituitary gland tissue-resident macrophages play a pivotal role in modulating hormonal balance
Authors: Lehtonen Henna , Jokela Heli , Hofmann Julian , Tola Lauriina , Mehmood Arfa , Ginhoux Florent , Becher Burkhard , Greter Melanie , Salmi Marko , Gerke Heidi , Rantakari Pia 
Published: May 2024

AbstractThe pituitary gland is the central endocrine regulatory organ underneath the brain, producing and releasing a variety of hormones that coordinate major body functions. The physical location of the pituitary gland underneath the brain, though outside the protective blood-brain barrier, leads to a unique immune environment of the pituitary that has not been studied. Here, we defined the development, diversity, spatial niche, and origin of the pituitary gland macrophage subsets using single cell transcriptomics, fate mapping, and imaging. We identified early yolk sac precursors solely seeding pituitary gland macrophages which are maintained by proliferation. Macrophage depletion experiments unveiled the essential contribution of early macrophages in the pituitary gland’s hormonal production and in modulating the post-pubertal expression of genes related to the sexually dimorphic processes regulated by the pituitary gland. Altogether, these findings provide novel information on pituitary gland macrophages and advance our understanding of immune-endocrine system crosstalk.
Accelerated growth increases the somatic epimutation rate in trees
Authors: Zhou M , Schmied G , Bradatsch M , Resente G , Hazarika R , Kakoulidou I , Costa M , Serra M , Uhl E , Schmitz RJ , Hilmers T , Toraño Caicoya A , Crivellaro A , Pretzsch H , Johannes F 
Published: May 2024

Trees are critical components of ecosystems and of major economic importance. Due to their extraordinary longevity and well-defined modular architecture they have also emerged as model systems to study the long-term accumulation of somatic mutations in plants. Coupled with retrospective life-history and environmental data, trees can offer unique insights into mutational processes that would be difficult to obtain with prospective studies. In addition to genetic mutations, somatic epimutations in the form of stochastic gains and losses of DNA cytosine methylation have been shown to accumulate rapidly during ontogeny. One hypothesis is that somatic epimutations originate from DNA methylation maintenance errors during mitotic cell divisions, which would predict that their rate of accumulation scales with growth rate, rather than with age.Here we test this hypothesis in European beech. We analyzed one of the oldest continuously measured experimental plots in the world. The plot contains an even-aged beech stand that was established in 1822 and monitored for growth at regular intervals until the present. Starting ∼150 years ago, alternative thinning strategies were applied to subplots of this experiment, resulting in differential stem growth rates among trees. We show that accelerated growth significantly increased the per-year somatic epimutation rate at CG dinucleotides, and that this effect is accompanied by differences in cell division rates. Hence, faster growth elevates the chances for methylation maintenance errors during DNA replication per unit time. As somatic CG epimutations can be stably inherited to subsequent generations in plants, our insights have direct ecological and evolutionary implications.
Epigenenomic and transcriptomic characterization ofNPM1-mutated CN-AML subtypes
Authors: N’Guyen Lia , Tellez-Quijorna Clara , Vernerey Julien , Garciaz Sylvain , Carbuccia Nadine , Guille Arnaud , Burny Claire , Poplineau Mathilde , Murati Anne , Hospital Marie-Anne , Vey Norbert , Birnbaum Daniel , Duprez Estelle 
Published: May 2024

ABSTRACTCytogenetic normal AML withNPM1mutations forms a distinct AML entity, associated with an intermediate prognosis and a heterogeneous response to treatment. We previously described an epigenetic biomarker, defined by the level of H3K27me3 on 70kb of theHIST1cluster in patient blast DNA. This epigenetic mark separates cytogenetically normalNPM1mutAML into two groups of patients differing in their survival rate following chemotherapy. To better characterize the influence of the biomarker on disease progression, we performed transcriptomic and histone mark profiling on patient blasts according to the level of H3K27me3HIST1. Our integrated analysis revealed that the two groups of patients display differences in terms of transcriptomic, chromatin landscape and cell surface markers, which could explain the clinical difference. Our profiling revealed novel targets and therefore constitutes an (epi)transcriptomic resource forNPM1AML. It also highlights the power of epigenetic profiling to dissect the heterogeneity of a single AML genetic entity.
BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer
Authors: Sriramulu Sushmitha , Thoidingjam Shivani , Chen Wei-Min , Hassan Oudai , Siddiqui Farzan , Brown Stephen L , Movsas Benjamin , Green Michael D , Davis Anthony J , Speers Corey , Walker Eleanor , Nyati Shyam 
Published: May 2024

AbstractBackgroundTriple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment.MethodsGene expression analysis was performed to look at genes upregulated in TNBC patient samples compared to other subtypes. Cell proliferation and clonogenic survivals assays determined the IC50of BUB1 inhibitor (BAY1816032) and radiation enhancement ratio (rER) with pharmacologic and genomic BUB1 inhibition. Mammary fat pad xenografts experiments were performed in CB17/SCID. The mechanism through which BUB1 inhibitor sensitizes TNBC cells to radiotherapy was delineated by γ-H2AX foci assays, BLRR, Immunoblotting, qPCR, CHX chase, and cell fractionation assays.ResultsBUB1 is overexpressed in BC and its expression is considerably elevated in TNBC with poor survival outcomes. Pharmacological or genomic ablation of BUB1 sensitized multiple TNBC cell lines to cell killing by radiation, although breast epithelial cells showed no radiosensitization with BUB1 inhibition. Kinase function of BUB1 is mainly accountable for this radiosensitization phenotype. BUB1 ablation also led to radiosensitization in TNBC tumor xenografts with significantly increased tumor growth delay and overall survival. Mechanistically, BUB1 ablation inhibited the repair of radiation-induced DNA double strand breaks (DSBs). BUB1 ablation stabilized phospho-DNAPKcs (S2056) following RT such that half-lives could not be estimated. In contrast, RT alone caused BUB1 stabilization, but pre-treatment with BUB1 inhibitor prevented stabilization (t1/2, ∼8 h). Nuclear and chromatin-enriched fractionations illustrated an increase in recruitment of phospho– and total-DNAPK, and KAP1 to chromatin indicating that BUB1 is indispensable in the activation and recruitment of non-homologous end joining (NHEJ) proteins to DSBs. Additionally, BUB1 staining of TNBC tissue microarrays demonstrated significant correlation of BUB1 protein expression with tumor grade.ConclusionsBUB1 ablation sensitizes TNBC cell lines and xenografts to RT and BUB1 mediated radiosensitization may occur through NHEJ. Together, these results highlight BUB1 as a novel molecular target for radiosensitization in women with TNBC.