bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma
Authors: Wu Yige , Terekhanova Nadezhda V. , Caravan Wagma , Naser Al Deen Nataly , Lal Preet , Chen Siqi , Mo Chia-Kuei , Cao Song , Li Yize , Karpova Alla , Liu Ruiyang , Zhao Yanyan , Shinkle Andrew , Strunilin Ilya , Weimholt Cody , Sato Kazuhito , Yao Lijun , Serasanambati Mamatha , Yang Xiaolu , Wyczalkowski Matthew , Zhu Houxiang , Zhou Daniel Cui , Jayasinghe Reyka G. , Mendez Daniel , Wendl Michael C. , Clark David , Newton Chelsea , Ruan Yijun , Reimers Melissa A. , Pachynski Russell K. , Kinsinger Chris , Jewell Scott , Chan Daniel W. , Zhang Hui , Chaudhuri Aadel A. , Chheda Milan G. , Humphreys Benjamin D. , Mesri Mehdi , Rodriguez Henry , Hsieh James J. , Ding Li , Chen Feng 
Published: March 2023

AbstractIdentifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival.CPknockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally,BAP1mutations are associated with widespread reduction of chromatin accessibility, whilePBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis.
Mechanism of antibody-specific deglycosylation and immune evasion by Streptococcal IgG-specific endoglycosidases
Authors: Trastoy Beatriz , Du Jonathan J. , Cifuente Javier O. , Rudolph Lorena , García-Alija Mikel , Klontz Erik H. , Deredge Daniel , Sultana Nazneen , Huynh Chau G. , Flowers Maria W. , Li Chao , Sastre Diego E. , Wang Lai-Xi , Corzana Francisco , Mallagaray Alvaro , Sundberg Eric J. , Guerin Marcelo E. 
Published: March 2023

AbstractBacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Streptococcus pyogenes serotypes secrete two multi-modular endo-β-N-acetylglucosaminidases, EndoS and EndoS2, that specifically deglycosylate the conserved N-glycan at Asn297 on IgG Fc, disabling antibody-mediated effector functions. Amongst thousands of known carbohydrate-active enzymes, EndoS and EndoS2 represent just a handful of enzymes that are specific to the protein portion of the glycoprotein substrate, not just the glycan component. Here, we present the cryoEM structure of EndoS in complex with the IgG1 Fc fragment. In combination with small-angle X-ray scattering, alanine scanning mutagenesis, hydrolytic activity measurements, enzyme kinetics, nuclear magnetic resonance and molecular dynamics analyses, we establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by EndoS and EndoS2. Our results provide a rational basis from which to engineer novel enzymes with antibody and glycan selectivity for clinical and biotechnological applications.
CEP peptide and cytokinin pathways converge on CEPD glutaredoxins to inhibit root growth
Authors: Taleski Michael , Chapman Kelly , Novák Ondřej , Schmülling Thomas , Frank Manuel , Djordjevic Michael A. 
Published: March 2023

AbstractC-TERMINALLY ENCODED PEPTIDE (CEP) and cytokinin hormones act over short and long distances to control plant responses to environmental cues. CEP and cytokinin pathway mutants share phenotypes, however, it is not known if these pathways intersect. We show that CEP and cytokinin signalling converge on CEP DOWNSTREAM (CEPD) glutaredoxins to inhibit primary root growth. CEP inhibition of root growth was impaired in mutants defective in trans-zeatin (tZ)-type cytokinin biosynthesis, transport, perception, and output. Concordantly, mutants affected in CEP RECEPTOR 1 showed reduced root growth inhibition in response to tZ, and altered levels of tZ-type cytokinins. Grafting and organ-specific hormone treatments showed that tZ-mediated root growth inhibition involved CEPD activity in roots. By contrast, root growth inhibition by CEP depended on shoot CEPD function. The results demonstrate that CEP and cytokinin pathways intersect, and utilise signalling circuits in separate organs involving common glutaredoxin genes to coordinate root growth.
Large haploblocks underlie rapid adaptation in the invasive weed Ambrosia artemisiifolia
Authors: Battlay Paul , Wilson Jonathan , Bieker Vanessa C. , Lee Christopher , Prapas Diana , Petersen Bent , Craig Sam , van Boheemen Lotte , Scalone Romain , de Silva Nissanka P. , Sharma Amit , Konstantinović Bojan , Nurkowski Kristin A. , Rieseberg Loren H. , Connallon Tim , Martin Michael D. , Hodgins Kathryn A. 
Published: March 2023

AbstractAdaptation is the central feature and leading explanation for the evolutionary diversification of life. Adaptation is also notoriously difficult to study in nature, owing to its complexity and logistically prohibitive timescale. Here, we leverage extensive contemporary and historical collections of Ambrosia artemisiifolia—an aggressively invasive weed and primary cause of pollen-induced hayfever—to track the phenotypic and genetic causes of recent local adaptation across its native and invasive ranges in North America and Europe, respectively. Large haploblocks—indicative of chromosomal inversions—contain a disproportionate share (26%) of genomic regions conferring parallel adaptation to local climates between ranges, are associated with rapidly adapting traits, and exhibit dramatic frequency shifts over space and time. These results highlight the importance of large-effect standing variants in rapid adaptation, which have been critical to A. artemisiifolia’s global spread across vast climatic gradients.
Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity
Authors: He Shuwen , Gillies John P. , Zang Juliana L. , Córdoba-Beldad Carmen M. , Yamamoto Io , Fujiwara Yasuhiro , Grantham Julie , DeSantis Morgan E. , Shibuya Hiroki 
Published: March 2023

AbstractSpindle formation in male meiosis relies on the canonical centrosome system, which is distinct from acentrosomal oocyte meiosis, but its specific regulatory mechanisms remain unknown. Herein, we report that DYNLRB2 (Dynein light chain roadblock-type-2) is a male meiosis-upregulated dynein light chain that is indispensable for spindle formation in meiosis I. In Dynlrb2 KO mouse testes, meiosis progression is arrested in metaphase I due to the formation of multipolar spindles with fragmented pericentriolar material (PCM). DYNLRB2 inhibits PCM fragmentation through two distinct pathways; suppressing premature centriole disengagement and targeting NuMA (nuclear mitotic apparatus) to spindle poles. The ubiquitously expressed mitotic counterpart, DYNLRB1, has similar roles in mitotic cells and maintains spindle bipolarity by targeting NuMA and suppressing centriole overduplication. Our work demonstrates that two distinct dynein complexes containing DYNLRB1 or DYNLRB2 are separately used in mitotic and meiotic spindle formations, respectively, and that both have NuMA as a common target.
Structural and functional analysis of human pannexin 2 channel
Authors: He Zhihui , Zhao Yonghui , Rau Michael J. , Fitzpatrick James A. J. , Sah Rajan , Hu Hongzhen , Yuan Peng 
Published: March 2023

AbstractThe pannexin 2 channel (PANX2) participates in multiple physiological processes including skin homeostasis, neuronal development, and ischemia-induced brain injury. However, the molecular basis of PANX2 channel function remains largely unknown. Here, we present a cryo-electron microscopy structure of human PANX2, which reveals pore properties contrasting with those of the intensely studied paralog PANX1. The extracellular selectivity filter, defined by a ring of basic residues, more closely resembles that of the distantly related volume-regulated anion channel (VRAC) LRRC8A, rather than PANX1. Furthermore, we show that PANX2 displays a similar anion permeability sequence as VRAC, and that PANX2 channel activity is inhibited by a commonly used VRAC inhibitor, DCPIB. Thus, the shared channel properties between PANX2 and VRAC may complicate dissection of their cellular functions through pharmacological manipulation. Collectively, our structural and functional analysis provides a framework for development of PANX2-specific reagents that are needed for better understanding of channel physiology and pathophysiology.
Functional comparison of metabolic networks across species
Authors: Ramon Charlotte , Stelling Jörg 
Published: March 2023

AbstractMetabolic phenotypes are pivotal for many areas, but disentangling how evolutionary history and environmental adaptation shape these phenotypes is an open problem. Especially for microbes, which are metabolically diverse and often interact in complex communities, few phenotypes can be determined directly. Instead, potential phenotypes are commonly inferred from genomic information, and rarely were model-predicted phenotypes employed beyond the species level. Here, we propose sensitivity correlations to quantify similarity of predicted metabolic network responses to perturbations, and thereby link genotype and environment to phenotype. We show that these correlations provide a consistent functional complement to genomic information by capturing how network context shapes gene function. This enables, for example, phylogenetic inference across all domains of life at the organism level. For 245 bacterial species, we identify conserved and variable metabolic functions, elucidate the quantitative impact of evolutionary history and ecological niche on these functions, and generate hypotheses on associated metabolic phenotypes. We expect our framework for the joint interpretation of metabolic phenotypes, evolution, and environment to help guide future empirical studies.
Unraveling a bifunctional mechanism for methanol-to-formate electro-oxidation on nickel-based hydroxides
Authors: Zhu Botao , Dong Bo , Wang Feng , Yang Qifeng , He Yunpeng , Zhang Cunjin , Jin Peng , Feng Lai 
Published: March 2023

AbstractFor nickel-based catalysts, in-situ formed nickel oxyhydroxide has been generally believed as the origin for anodic biomass electro-oxidations. However, rationally understanding the catalytic mechanism still remains challenging. In this work, we demonstrate that NiMn hydroxide as the anodic catalyst can enable methanol-to-formate electro-oxidation reaction (MOR) with a low cell-potential of 1.33/1.41 V at 10/100 mA cm−2, a Faradaic efficiency of nearly 100% and good durability in alkaline media, remarkably outperforming NiFe hydroxide. Based on a combined experimental and computational study, we propose a cyclic pathway that consists of reversible redox transitions of NiII-(OH)2/NiIII-OOH and a concomitant MOR. More importantly, it is proved that the NiIII-OOH provides combined active sites including NiIIIand nearby electrophilic oxygen species, which work in a cooperative manner to promote either spontaneous or non-spontaneous MOR process. Such a bifunctional mechanism can well account for not only the highly selective formate formation but also the transient presence of NiIII-OOH. The different catalytic activities of NiMn and NiFe hydroxides can be attributed to their different oxidation behaviors. Thus, our work provides a clear and rational understanding of the overall MOR mechanism on nickel-based hydroxides, which is beneficial for advanced catalyst design.
Neuraminidase 1 promotes renal fibrosis development in male mice
Authors: Chen Qian-Qian , Liu Kang , Shi Ning , Ma Gaoxiang , Wang Peipei , Xie Hua-Mei , Jin Si-Jia , Wei Ting-Ting , Yu Xiang-Yu , Wang Yi , Zhang Jun-Yuan , Li Ping , Qi Lian-Wen , Zhang Lei 
Published: March 2023

AbstractThe functions of the influenza virus neuraminidase has been well documented but those of the mammalian neuraminidases remain less explored. Here, we characterize the role of neuraminidase 1 (NEU1) in unilateral ureteral obstruction (UUO) and folic acid (FA)-induced renal fibrosis mouse models. We find that NEU1 is significantly upregulated in the fibrotic kidneys of patients and mice. Functionally, tubular epithelial cell-specific NEU1 knockout inhibits epithelial-to-mesenchymal transition, inflammatory cytokines production, and collagen deposition in mice. Conversely, NEU1 overexpression exacerbates progressive renal fibrosis. Mechanistically, NEU1 interacts with TGFβ type I receptor ALK5 at the 160-200aa region and stabilizes ALK5 leading to SMAD2/3 activation. Salvianolic acid B, a component of Salvia miltiorrhiza, is found to strongly bind to NEU1 and effectively protect mice from renal fibrosis in a NEU1-dependent manner. Collectively, this study characterizes a promotor role for NEU1 in renal fibrosis and suggests a potential avenue of targeting NEU1 to treat kidney diseases.
The small GTPase Rit2 modulates LRRK2 kinase activity, is required for lysosomal function and protects against alpha-synuclein neuropathology
Authors: Obergasteiger Julia , Castonguay Anne-Marie , Pizzi Sara , Magnabosco Stefano , Frapporti Giulia , Lobbestael Evy , Baekelandt Veerle , Hicks Andrew A. , Pramstaller Peter P. , Gravel Claude , Corti Corrado , Lévesque Martin , Volta Mattia 
Published: March 2023

AbstractIn Parkinson’s disease (PD) misfolded alpha-synuclein (aSyn) accumulates in the substantia nigra, where dopaminergic neurons are progressively lost. The mechanisms underlying aSyn pathology are still unclear, but they are hypothesized to involve the autophagy-lysosome pathway (ALP). LRRK2 mutations are a major cause of familial and sporadic PD, and LRRK2 kinase activity has been shown to be involved in pS129-aSyn inclusion modulation. We observed selective downregulation of the novel PD risk factor RIT2 in vitro and in vivo. Rit2 overexpression in G2019S-LRRK2 cells rescued ALP abnormalities and diminished aSyn inclusions. In vivo, viral mediated overexpression of Rit2 operated neuroprotection against AAV-A53T-aSyn. Furthermore, Rit2 overexpression prevented the A53T-aSyn-dependent increase of LRRK2 kinase activity in vivo. On the other hand, reduction of Rit2 levels leads to defects in the ALP, similar to those induced by the G2019S-LRRK2 mutation. Our data indicate that Rit2 is required for correct lysosome function, inhibits overactive LRRK2 to ameliorate ALP impairment, and counteracts aSyn aggregation and related deficits. Targeting Rit2 could represent an effective strategy to combat neuropathology in familial and idiopathic PD.
Symptoms assessment and decision to treat patients with advanced Parkinson’s disease based on wearables data
Authors: Virbel-Fleischman Clara , Mousin Flavien , Liu Shuo , Hardy Sébastien , Corvol Jean-Christophe , Benatru Isabelle , Bendetowicz David , Béreau Matthieu , De Cock Valérie Cochen , Drapier Sophie , Frismand Solène , Giordana Caroline , Devos David , Rétory Yann , Grabli David 
Published: March 2023

AbstractBody-worn sensors (BWS) could provide valuable information in the management of Parkinson’s disease and support therapeutic decisions based on objective monitoring. To study this pivotal step and better understand how relevant information is extracted from BWS results and translated into treatment adaptation, eight neurologists examined eight virtual cases composed of basic patient profiles and their BWS monitoring results. Sixty-four interpretations of monitoring results and the subsequent therapeutic decisions were collected. Relationship between interrater agreements in the BWS reading and the severity of symptoms were analyzed via correlation studies. Logistic regression was used to identify associations between the BWS parameters and suggested treatment modifications. Interrater agreements were high and significantly associated with the BWS scores. Summarized BWS scores reflecting bradykinesia, dyskinesia, and tremor predicted the direction of treatment modifications. Our results suggest that monitoring information is robustly linked to treatment adaptation and pave the way to loop systems able to automatically propose treatment modifications from BWS recordings information.
A survey on dogs with valvular disease flying to Japan for operation
Authors: Takahashi Arane , Takeuchi Sayaka , Chen Ayaka , Uechi Masami 
Published: March 2023

AbstractIn small-breed dogs, myxomatous mitral valve disease (MMVD) is a common disease which may lead to chronic heart failure. Mitral valve repair is an optimal surgical treatment that is currently available in limited veterinary facilities globally because it requires a special surgery team and specific devices. Therefore, some dogs must travel overseas to undergo this surgery. However, a question arises regarding the safety of dogs when traveling by air with a heart disease. We aimed to evaluate the effect of flight journey on dogs with mitral valve disease, including survival rates, symptoms during the trip, laboratory test results, and operational outcomes. All dogs stayed near the owner in the cabin during the flight. The survival rate after the flight was 97.5% in 80 dogs. The surgical survival rates (96.0% and 94.3%) and hospitalization periods (7 days and 7 days) were similar between overseas and domestic dogs. This report shows that taking air flights in the cabin may not have a significant effect on dogs with MMVD, on the premise that their overall conditions are stable under cardiac medication.
Terrestrial planet and asteroid belt formation by Jupiter–Saturn chaotic excitation
Authors: Lykawka Patryk Sofia , Ito Takashi 
Published: March 2023

AbstractThe terrestrial planets formed by accretion of asteroid-like objects within the inner solar system’s protoplanetary disk. Previous works have found that forming a small-mass Mars requires the disk to contain little mass beyond ~ 1.5 au (i.e., the disk mass was concentrated within this boundary). The asteroid belt also holds crucial information about the origin of such a narrow disk. Several scenarios may produce a narrow disk. However, simultaneously replicating the four terrestrial planets and the inner solar system properties remains elusive. Here, we found that chaotic excitation of disk objects generated by a near-resonant configuration of Jupiter–Saturn can create a narrow disk, allowing the formation of the terrestrial planets and the asteroid belt. Our simulations showed that this mechanism could typically deplete a massive disk beyond ~ 1.5 au on a 5–10 Myr timescale. The resulting terrestrial systems reproduced the current orbits and masses of Venus, Earth and Mars. Adding an inner region disk component within ~ 0.8–0.9 au allowed several terrestrial systems to simultaneously form analogues of the four terrestrial planets. Our terrestrial systems also frequently satisfied additional constraints: Moon-forming giant impacts occurring after a median ~ 30–55 Myr, late impactors represented by disk objects formed within 2 au, and effective water delivery during the first 10–20 Myr of Earth’s formation. Finally, our model asteroid belt explained the asteroid belt’s orbital structure, small mass and taxonomy (S-, C- and D/P-types).
Root cause prediction for failures in semiconductor industry, a genetic algorithm–machine learning approach
Authors: Rammal Abbas , Ezukwoke Kenneth , Hoayek Anis , Batton-Hubert Mireille 
Published: March 2023

AbstractFailure analysis has become an important part of guaranteeing good quality in the electronic component manufacturing process. The conclusions of a failure analysis can be used to identify a component’s flaws and to better understand the mechanisms and causes of failure, allowing for the implementation of remedial steps to improve the product’s quality and reliability. A failure reporting, analysis, and corrective action system is a method for organizations to report, classify, and evaluate failures, as well as plan corrective actions. These text feature datasets must first be preprocessed by Natural Language Processing techniques and converted to numeric by vectorization methods before starting the process of information extraction and building predictive models to predict failure conclusions of a given failure description. However, not all-textual information is useful for building predictive models suitable for failure analysis. Feature selection has been approached by several variable selection methods. Some of them have not been adapted for use in large data sets or are difficult to tune and others are not applicable to textual data. This article aims to develop a predictive model able to predict the failure conclusions using the discriminating features of the failure descriptions. For this, we propose to combine a Genetic Algorithm with supervised learning methods for an optimal prediction of the conclusions of failure in terms of the discriminant features of failure descriptions. Since we have an unbalanced dataset, we propose to apply an F1 score as a fitness function of supervised classification methods such as Decision Tree Classifier and Support Vector Machine. The suggested algorithms are called GA-DT and GA-SVM. Experiments on failure analysis textual datasets demonstrate the effectiveness of the proposed GA-DT method in creating a better predictive model of failure conclusion compared to using the information of the entire textual features or limited features selected by a genetic algorithm based on a SVM. Quantitative performances such as BLEU score and cosine similarity are used to compare the prediction performance of the different approaches.
Exploiting machine learning models to identify novel Alzheimer’s disease biomarkers and potential targets
Authors: Alamro Hind , Thafar Maha A. , Albaradei Somayah , Gojobori Takashi , Essack Magbubah , Gao Xin 
Published: March 2023

AbstractWe still do not have an effective treatment for Alzheimer's disease (AD) despite it being the most common cause of dementia and impaired cognitive function. Thus, research endeavors are directed toward identifying AD biomarkers and targets. In this regard, we designed a computational method that exploits multiple hub gene ranking methods and feature selection methods with machine learning and deep learning to identify biomarkers and targets. First, we used three AD gene expression datasets to identify 1/ hub genes based on six ranking algorithms (Degree, Maximum Neighborhood Component (MNC), Maximal Clique Centrality (MCC), Betweenness Centrality (BC), Closeness Centrality, and Stress Centrality), 2/ gene subsets based on two feature selection methods (LASSO and Ridge). Then, we developed machine learning and deep learning models to determine the gene subset that best distinguishes AD samples from the healthy controls. This work shows that feature selection methods achieve better prediction performances than the hub gene sets. Beyond this, the five genes identified by both feature selection methods (LASSO and Ridge algorithms) achieved an AUC = 0.979. We further show that 70% of the upregulated hub genes (among the 28 overlapping hub genes) are AD targets based on a literature review and six miRNA (hsa-mir-16-5p, hsa-mir-34a-5p, hsa-mir-1-3p, hsa-mir-26a-5p, hsa-mir-93-5p, hsa-mir-155-5p) and one transcription factor, JUN, are associated with the upregulated hub genes. Furthermore, since 2020, four of the six microRNA were also shown to be potential AD targets. To our knowledge, this is the first work showing that such a small number of genes can distinguish AD samples from healthy controls with high accuracy and that overlapping upregulated hub genes can narrow the search space for potential novel targets.