bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-organ metabolic model of tomato predicts plant responses to nutritional and genetic perturbations
Authors: Gerlin Léo , Cottret Ludovic , Escourrou Antoine , Genin Stéphane , Baroukh Caroline 
Published: October 2021

AbstractPredicting and understanding plant responses to perturbations requires integrating the interactions between nutritional sources, genes, cell metabolism and physiology in the same model. This can be achieved using metabolic modeling calibrated by experimental data. In this study, we developed a multi-organ metabolic model of a tomato plant during vegetative growth, named VYTOP (Virtual Young TOmato Plant) that combines genome-scale metabolic models of leaf, stem and root and integrates experimental data acquired from metabolomics and high-throughput phenotyping of tomato plants. It is composed of 6689 reactions and 6326 metabolites. We validated VYTOP predictions on five independent use cases. The model correctly predicted that glutamine is the main organic nutrient of xylem sap. The model estimated quantitatively how stem photosynthetic contribution impact exchanges between the different organs. The model was also able to predict how nitrogen limitation affects the plant vegetative growth, and to predict the metabolic behavior of transgenic tomato lines with altered expressions of core metabolic enzymes. The integration of different components such as a metabolic model, physiological constraints and experimental data generates a powerful predictive tool to study plant behavior, which will be useful for several other applications such as plant metabolic engineering or plant nutrition.One sentence summaryA multi-organ metabolic model of tomato gives biological insights into the functioning of a plant such as xylem composition, the role of the stem and the response to environmental or genetic perturbation.
Hi-C detects genomic structural variants in peripheral blood of pediatric leukemia patients
Authors: Mallard Claire , Johnston Michael J , Bobyn Anna , Nikolic Ana , Argiropoulos Bob , Chan Jennifer A , Guilcher Gregory MT , Gallo Marco 
Published: October 2021

ABSTRACTB-cell acute lymphoblastic leukemia (B-ALL) is often driven by chromosome translocations that result in recurrent and well-studied gene fusions. Currently, fluorescent in-situ hybridization probes are employed to detect candidate translocations in bone marrow samples from B-ALL patients. Recently Hi-C, a sequencing-based technique originally designed to reconstruct the three-dimensional architecture of the nuclear genome, was shown to effectively recognize structural variants. Here, we demonstrate that Hi-C can be used as a genome-wide assay to detect translocations and other structural variants of potential clinical interest. Structural variants were identified in both bone marrow and peripheral blood samples, including an ETV6-RUNX1 translocation present in one pediatric B-ALL patient. Our report provides proof-of-principle that Hi-C could be an effective strategy to globally detect driver structural variants in B-ALL peripheral blood specimens, reducing the need for invasive bone marrow biopsies and candidate-based clinical tests.
SARS-CoV-2 multi-variant graphene biosensor based on engineered dimeric ACE2 receptor
Authors: D’Agostino Mattia , Pavoni Eleonora , Romagnoli Alice , Ardiccioni Chiara , Motta Stefano , Crippa Paolo , Biagetti Giorgio , Notarstefano Valentina , Barocci Simone , Costabile Brianna K. , Colasurdo Gabriele , Caucci Sara , Mencarelli Davide , Turchetti Claudio , Farina Marco , Pierantoni Luca , Teana Anna La , Hadi Richard Al , Chinappi Mauro , Trucchi Emiliano , Mancia Filippo , Morozzo della Rocca Blasco , D’Annessa Ilda , Marino Daniele Di 
Published: October 2021

AbstractFast, reliable and point-of-care systems to detect the SARS-CoV-2 infection are crucial to contain viral spreading and to adopt timely clinical treatments. Many of the rapid detection tests currently in use are based on antibodies that bind viral proteins1. However, newly appearing virus variants accumulate mutations in their RNA sequence and produce proteins, such as Spike, that may show reduced binding affinity to these diagnostic antibodies, resulting in less reliable tests and in the need for continuous update of the sensing systems2. Here we propose a graphene field-effect transistor (gFET) biosensor which exploits the key interaction between the Spike protein and the human ACE2 receptor. This interaction is one of the determinants of host infections and indeed recently evolved Spike variants were shown to increase affinity for ACE2 receptor3. Through extensive computational analyses we show that a chimeric ACE2-Fc construct mimics the ACE2 dimer, normally present on host cells membranes, better than its soluble truncated form. We demonstrate that ACE2-Fc functionalized gFET is effective for in vitro detection of Spike and outperforms the same chip functionalized with either a diagnostic antibody or the soluble ACE2. Our sensor is implemented in a portable, wireless, point-of-care device and successfully detected both alpha and gamma virus variants in patient’s clinical samples. As incomplete immunization, due to vaccine roll-out, may offer new selective grounds for antibody-escaping virus variants4, our biosensor opens to a class of highly sensitive, rapid and variant-robust SARS-CoV-2 detection systems.
Impact of Salivary and Pancreatic Amylase Gene Copy Numbers on Diabetes, Obesity, and Functional Profiles of Microbiome in Northern Japanese Population
Authors: Hasegawa Takanori , Kakuta Masanori , Yamaguchi Rui , Sato Noriaki , Mikami Tatsuya , Murashita Koichi , Nakaji Shigeyuki , Itoh Ken , Imoto Seiya 
Published: October 2021

AbstractAmylase genes reside in a structurally complex locus, and their copy numbers vary greatly, especially among agricultural races. Amylase genes seem to shape the metabolic response to dietary starch, and several studies have reported their association with obesity. Besides, the effect of amylase copy numbers seems to depend on lifestyle, and the mechanism of this effect was partially explained by changes in the oral and gut microbiome compositions; however, a detailed mechanism has been unclarified. In this study, we showed their association with diabetes in addition to obesity, and further discovered a plausible mechanism of this association based on the function of commensal bacterial in a northern Japanese population. First, we confirmed that the amylase copy number in the population tends to be larger than that reported in other studies and that there is a positive association between obesity and diabetes (p =1.95E-2 and 3.28E-2). Second, we identified that relative abundance of some genus level microbiome, Capnocytophaga, Dialister, and previously reported bacteria, were significantly associated with amylase copy numbers. Finally, through functional gene-set analysis using shotgun sequencing, we observed that the abundance of genes in the Acarbose pathway in the gut microbiome was significantly decreased with an increase in the amylase copy number (p-value = 5.80E-4), which can partly explain the mechanism underlying obesity and diabetes in populations with high amylase copy numbers.
Clinical evaluation of a RT-LAMP SARS-CoV-2 test for the Point-Of-Care, rapid, low-cost, integrating sample solid phase extraction and on which reagents are lyophilized
Authors: Coz E. , Garneret P. , Martin E. , do Nascimento D. F. , Vilquin A. , Hoinard D. , Feher M. , Grassin Q. , Vanhomwegen J. , Manuguerra J.C , Mukherjee S. , Olivo-Marin J.-C. , Brient-Litzler E. , Merzoug M. , Collin E. , Tabeling P. , Rossi B. 
Published: October 2021

ABSTRACTObjectivesDetermine the sensitivity and specificity of a Point-Of-Care test (‘COVIDISC’) for SARS-COV2. The novelty of the test is to integrate, on the same (low-cost) compact plastic/paper device, solid phase RNA extraction and RT-LAMP amplification, all reagents being freeze-dried on it.MethodRetrospective study with a cohort of 99 patients characterized by real-time RT-PCR. The 37 positive naso-pharyngeal samples cover a broad range of viral loads (from 5 gc /µL to 2 106gc/ µL of sample).ResultsThe COVIDISC found 36 positives (out of 37 by IP4 RT-PCR protocols) and 63 negatives (out of 62 by RT-PCR).ConclusionThe sensitivity of the COVIDISC, found in this 99-patient retrospective study, is 97% and the specificity 100%.
In vivo CRISPRi screen reveals the differential requirement for mitochondrial respiratory chain function between in vivo and in vitro tumor growth
Authors: Nakaoka Hiroki , Bennett Neal , Okimoto Ross A. , Laurent Danny , Sei Yoshitaka , Bivona Trever , Hoeve Johanna ten , Graeber Thomas G. , Nakamura Ken , Nakamura Jean L. 
Published: October 2021

ABSTRACTThe Warburg effect, aerobic glycolysis, is a hallmark feature of cancer cells grown in culture. However, the relative roles of glycolysis and respiratory metabolism in supporting in vivo tumor growth and significant processes such as tumor dissemination and metastases remain poorly understood, particularly on a systems level. Using a CRISPRi mini-library enriched for mitochondrial ribosomal protein and respiratory chain genes in multiple human lung cancer cell lines we analyzed in vivo metabolic requirements in xenograft tumors grown in distinct anatomic contexts. While knockdown of mitochondrial ribosomal protein and respiratory chain genes (mito-respiratory genes) has little impact on growth in vitro, tumor cells depend heavily on these genes when grown in vivo as either flank or primary orthotopic lung tumor xenografts. In contrast, respiratory function is comparatively dispensable for metastatic tumor growth. RNA-Seq and metabolomics analysis of tumor cells expressing individual sgRNAs against mito-respiratory genes indicate overexpression of glycolytic genes and increased sensitivity of glycolytic inhibition compared to control when grown in vitro, but when grown in vivo as primary tumors these cells downregulate glycolytic mechanisms. These studies demonstrate that discrete perturbations of mitochondrial metabolism impact in vivo tumor growth in a context-specific manner and provides systems-level evidence that respiratory function modulates tumor growth in vivo, suggesting that ATP limits growth and metastatic potential.
Inherited variants in CHD3 demonstrate variable expressivity in Snijders Blok-Campeau syndrome
Authors: van der Spek Jet , den Hoed Joery , Snijders Blok Lot , Dingemans Alexander J. M. , Schijven Dick , Nellaker Christoffer , Venselaar Hanka , Barakat Tahsin Stefan , Bebin E. Martina , Beck-Wödl Stefanie , Beunders Gea , Brown Natasha J. , Brunet Theresa , Brunner Han G. , Campeau Philippe M. , Čuturilo Goran , Gilissen Christian , Haack Tobias B. , Husain Ralf A. , Kamien Benjamin , Lim Sze Chern , Lovrecic Luca , Magg Janine , Maver Ales , Miranda Valancy , Monteil Danielle C. , Ockeloen Charlotte W. , Pais Lynn S. , Plaiasu Vasilica , Raiti Laura , Richmond Christopher , Rieß Angelika , Schwaibold Eva M. C. , Simon Marleen E. H. , Spranger Stephanie , Tan Tiong Yang , Thompson Michelle L. , de Vries Bert B.A. , Wilkins Ella J. , Willemsen Marjolein H. , Francks Clyde , Vissers Lisenka E. L. M. , Fisher Simon E. , Kleefstra Tjitske 
Published: October 2021

SummaryInterpretation of next-generation sequencing data of individuals with an apparent sporadic neurodevelopmental disorder (NDD) often focusses on pathogenic variants in genes associated with NDD, assuming full clinical penetrance with limited variable expressivity. Consequently, inherited variants in genes associated with dominant disorders may be overlooked when the transmitting parent is clinically unaffected. While de novo variants explain a substantial proportion of cases with NDDs, a significant number remains undiagnosed possibly explained by coding variants associated with reduced penetrance and variable expressivity. We characterized twenty families with inherited heterozygous missense or protein-truncating variants (PTVs) in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome, characterized by intellectual disability, speech delay and recognizable facial features (SNIBCPS). Notably, the majority of the inherited CHD3 variants were maternally transmitted. Computational facial and human phenotype ontology-based comparisons demonstrated that the phenotypic features of probands with inherited CHD3 variants overlap with the phenotype previously associated with de novo variants in the gene, while carrier parents are mildly or not affected, suggesting variable expressivity. Additionally, similarly reduced expression levels of CHD3 protein in cells of an affected proband and of related healthy carriers with a CHD3 PTV, suggested that compensation of expression from the wildtype allele is unlikely to be an underlying mechanism. Our results point to a significant role of inherited variation in SNIBCPS, a finding that is critical for correct variant interpretation and genetic counseling and warrants further investigation towards understanding the broader contributions of such variation to the landscape of human disease.
Molecular Basis of Urostyle Development: Genes and Gene Regulation Underlying an Evolutionary Novelty
Authors: Senevirathne Gayani , Shubin Neil H. 
Published: October 2021

ABSTRACTEvolutionary novelties entail the origin of morphologies that enable new functions. These features can arise through changes to gene function and regulation. One important novelty is the fused rod at the end of the vertebral column in anurans, the urostyle. This feature is composed of a coccyx and an ossifying hypochord, and both structures ossify during metamorphosis. We used Laser Capture Micro-dissection of these identified tissues and subjected them to RNA-seq and ATAC-seq analyses at three developmental stages in tadpoles of Xenopus tropicalis. These experiments reveal that the coccyx and hypochord have two different molecular signatures. ATAC-seq data reveals potential regulatory regions that are observed in proximity to candidate genes identified from RNA-seq. Neuronal (TUBB3) and muscle markers (MYH3) are upregulated in coccygeal tissues, whereas T-box genes (TBXT, TBXT.2), corticosteroid stress hormones (CRCH.1), and matrix metallopeptidases (MMP1, MMP8, MMP13) are upregulated in the hypochord. Even though an ossifying hypochord is only present in anurans, this ossification between the vertebral column and the notochord appears to resemble a congenital vertebral anomaly seen prenatally in humans, caused by an ectopic expression of the TBXT/TBXT.2 gene. This work opens the way to functional studies that help us better elucidate anuran bauplan evolution.
Archerfish number discrimination
Authors: Potrich Davide , Zanon Mirko , Vallortigara Giorgio 
Published: October 2021

ABSTRACTDebates have arisen as to whether non-human animals actually can learn astract non-symbolic numerousness or whether they always rely on some continuous physical aspect of the stimuli covarying with number. Here we investigated archerfish (Toxotes jaculatrix) non-symbolic numerical discrimination with accurate control for co-varying continuous physical stimulus attributes. Archerfish were trained to select one of two groups of black dots (Exp. 1: 3 vs. 6 elements; Exp. 2: 2 vs. 3 elements); these were controlled for several combinations of physical variables (elements’ size, overall area, overall perimeter, density and sparsity), ensuring that only numerical information was available. Generalization tests with novel numerical comparisons (2 vs. 3, 5 vs. 8 and 6 vs. 9 in Exp. 1; 3 vs. 4, 3 vs. 6 in Exp. 2) revealed choice for the largest or smallest numerical group according to the relative number that was rewarded at training. None of the continuous physical variables, including spatial frequency, were affecting archerfish performance. Results provide evidence of the spontaneous use of abstract relative numerical information in archerfish for both small and large numbers.
Disruption of metapopulation structure effectively reduces Tasmanian devil facial tumour disease spread at the expense of abundance and genetic diversity
Authors: Durrant Rowan , Hamede Rodrigo , Wells Konstans , Lurgi Miguel 
Published: October 2021

AbstractMetapopulation structure (i.e. the spatial arrangement of local populations and corridors between them) plays a fundamental role in the persistence of wildlife populations, but can also drive the spread of infectious diseases. While the disruption of metapopulation connectivity can reduce disease spread, it can also impair host resilience by disrupting gene flow and colonisation dynamics. Thus, a pressing challenge for many wildlife populations is to elucidate whether the benefits of disease management methods that reduce metapopulation connectivity outweigh the associated risks.Directly transmissible cancers are clonal malignant cell lines capable to spread through host populations without immune recognition, when susceptible and infected hosts become in close contact. Using an individual-based metapopulation model we investigate the effects of the interplay between host dispersal, disease transmission rate and inter-individual contact distance for transmission (determining within-population mixing) on the spread and persistence of a transmissible cancer, Tasmanian devil facial tumour disease (DFTD), from local to regional scales. Further, we explore population isolation scenarios to devise management strategies to mitigate disease spread.Disease spread, and the ensuing population declines, are synergistically determined by individuals’ dispersal, disease transmission rate and within-population mixing. Low to intermediate transmission rates can be magnified by high dispersal and inter-individual transmission distance. Once disease transmission rate is high, dispersal and inter-individual contact distance do not impact the outcome of the disease transmission dynamics.Isolation of local populations effectively reduced metapopulation-level disease prevalence but caused severe declines in metapopulation size and genetic diversity. The relative position of managed (i.e. isolated) populations within the metapopulation had a significant effect on disease prevalence, highlighting the importance of considering metapopulation structure when implementing metapopulation-scale disease control measures. Our findings suggests that population isolation is not an ideal management method for preventing disease spread in species inhabiting already fragmented landscapes, where genetic diversity and extinction risk are already a concern, such as the Tasmanian devil.
A synthesis of senescence predictions for indeterminate growth, and support from multiple tests in wild lake trout
Authors: Purchase Craig F. , Rooke Anna C. , Gaudry Michael J. , Treberg Jason R. , Mittell Elizabeth A. , Morrissey Michael B. , Rennie Michael D. 
Published: October 2021

ABSTRACTSenescence, or the deterioration of functionality with age, varies widely across taxa in pattern and rate. Insights into why and how this variation occurs are hindered by the predominance of lab-focused research on short-lived model species with determinate growth. We synthesize evolutionary theories of senescence, highlight key information gaps, and clarify predictions for species with low mortality and variable degrees of indeterminate growth. Lake trout are an ideal species to evaluate predictions in the wild. We monitored individual males from two populations (1976-2017) longitudinally for changes in adult mortality (actuarial senescence) and body condition (proxy for energy balance). A cross-sectional approach (2017) compared young (ages 4-10 years) and old (18-37 years) adults for (1) phenotypic performance in body condition, and semen quality - which is related to fertility under sperm competition (reproductive senescence), and (2) relative telomere length (potential proxy for cellular senescence). Adult growth in these particular populations is constrained by a simplified food web, and our data support predictions of negligible senescence when maximum size is only slightly larger than maturation size. Negative senescence (aka reverse senescence) may occur in other lake trout populations where diet shifts allow maximum sizes to be much larger than maturation size.
Network-aware credit scoring system for telecom subscribers using machine learning and network analysis
Authors: Gao Hongming , Liu Hongwei , Ma Haiying , Ye Cunjun , Zhan Mingjun 
Published: October 2021

PurposeA good decision support system for credit scoring enables telecom operators to measure the subscribers' creditworthiness in a fine-grained manner. This paper aims to propose a robust credit scoring system by leveraging latent information embedded in the telecom subscriber relation network based on multi-source data sources, including telecom inner data, online app usage, and offline consumption footprint.Design/methodology/approachRooting from network science, the relation network model and singular value decomposition are integrated to infer different subscriber subgroups. Employing the results of network inference, the paper proposed a network-aware credit scoring system to predict the continuous credit scores by implementing several state-of-art techniques, i.e. multivariate linear regression, random forest regression, support vector regression, multilayer perceptron, and a deep learning algorithm. The authors use a data set consisting of 926 users of a Chinese major telecom operator within one month of 2018 to verify the proposed approach.FindingsThe distribution of telecom subscriber relation network follows a power-law function instead of the Gaussian function previously thought. This network-aware inference divides the subscriber population into a connected subgroup and a discrete subgroup. Besides, the findings demonstrate that the network-aware decision support system achieves better and more accurate prediction performance. In particular, the results show that our approach considering stochastic equivalence reveals that the forecasting error of the connected-subgroup model is significantly reduced by 7.89–25.64% as compared to the benchmark. Deep learning performs the best which might indicate that a non-linear relationship exists between telecom subscribers' credit scores and their multi-channel behaviours.Originality/valueThis paper contributes to the existing literature on business intelligence analytics and continuous credit scoring by incorporating latent information of the relation network and external information from multi-source data (e.g. online app usage and offline consumption footprint). Also, the authors have proposed a power-law distribution-based network-aware decision support system to reinforce the prediction performance of individual telecom subscribers' credit scoring for the telecom marketing domain.