bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortical cell size regulates root metabolic cost
Authors: Sidhu Jagdeep Singh , Lynch Jonathan P. 
Published: August 2023

AbstractIt has been hypothesized that vacuolar occupancy in mature root cortical parenchyma cells regulates root metabolic cost and thereby plant fitness under conditions of drought, suboptimal nutrient availability, and soil mechanical impedance. However, the mechanistic role of vacuoles in reducing root metabolic cost was unproven. Here we provide evidence to support this hypothesis. We first show that root cortical cell size is determined by both cortical cell diameter (CCD) and cell length (CCL). Significant genotypic variation for both CCD (∼1.1 to 1.5- fold) and CCL (∼ 1.3 to 7-fold) was observed in maize and wheat. GWAS and QTL analyses indicate CCD and CCL are heritable and under independent genetic control. We identify candidate genes for both phenes. Empirical results from isophenic lines contrasting for CCD and CCL show that increased cell size, due to either CCD or CCL, is associated with reduced root respiration, root nitrogen content, and root phosphorus content.RootSlice, a functional-structural model of root anatomy, predicts that an increased ratio of vacuolar to cytoplasmic volume causes reduced root respiration and tissue nutrient content. Ultrastructural imaging of cortical parenchyma cells with varying CCD and CCL confirms thein-silicopredictions and shows that an increase in cell size is correlated with increased vacuolar volume and reduced cytoplasmic volume. Phylogenetic analysis of terrestrial plants reveals that CCD has not significantly changed throughout plant evolution. Vacuolar occupancy and its relationship with CCD/CCL merits further investigation as a phene for improving crop adaptation to edaphic stress.Significance StatementCortical cell size is an important phene determining root metabolic cost, but the underlying physiological mechanism is unclear. Here, usingin silicoand empirical approaches, we provide evidence that supports the hypothesis that vacuolar occupancy in cortical parenchyma cells regulates root metabolic cost. We also show that vacuolar occupancy is associated with cortical cell diameter and cell length, phenes that are under distinct genetic control and hold the potential for improving crop yields under edaphic stress.
Progressive plasticity during colorectal cancer metastasis
Authors: Moorman AR , Cambuli F , Benitez EK , Jiang Q , Xie Y , Mahmoud A , Lumish M , Hartner S , Balkaran S , Bermeo J , Asawa S , Firat C , Saxena A , Luthra A , Sgambati V , Luckett K , Wu F , Li Y , Yi Z , Masilionis I , Soares K , Pappou E , Yaeger R , Kingham P , Jarnagin W , Paty P , Weiser MR , Mazutis L , D’Angelica M , Shia J , Garcia-Aguilar J , Nawy T , Hollmann TJ , Chaligné R , Sanchez-Vega F , Sharma R , Pe’er D , Ganesh K 
Published: August 2023

AbstractMetastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5+intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.
ABCB7 deficiency increases endoplasmic reticulum–mitochondria coupling and mTOR-independent autophagy flux in H9c2 cardiomyocytes
Authors: Chandan Shivanshu , Kosher Ganesh 
Published: August 2023

AbstractABCB7 deficiency during chronic cardiac hypertrophy contribute to mitochondrial dysfunction, metabolic shift and worsens cardiac function. Here, we explored that ABCB7 deficiency contribute to tethering of mito-ER and in turn mitochondrial dysfunction in H9c2 cells. We also investigated the mechanistic link between mitochondrial dysfunction and ABCB7 deficiency in these cells. Knockdown of ABCB7 was performed by siABCB7 plasmids or control vectors using lipofectamine 2000. To rescue the changes produced by siABCB7, ABCB7 overexpression was performed using ABCB7 overexpression vector. After knockdown or overexpression, cells were harvested for transmission electron microscopy (TEM), RT-PCR or Immunofluorescence analysis. Knockdown of ABCB7 in H9C2 cells resulted in enhanced tethering of mito.-ER contact sites, and increased mito.-ER distance. To our surprise, the downregulation of ABCB7 did not alter the cristae structure or morphology in these cells. On the mechanistic front, Knockdown of ABCB7 in H9C2 cells MTOR-independent AMPK-dependent macroautophagic/autophagic flux. ABCB7 downregulation did not result in cell death in these cells; this phenomenon could work independent of cell death in H9c2 cells.
GPATCH11variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment
Authors: Zanetti Andrea , Fares-Taie Lucas , Amiel Jeanne , Roger Jérôme , Audo Isabelle , Robert Matthieu , David Pierre , Jung Vincent , Goudin Nicolas , Guerrera Ida Chiara , Moriceau Stéphanie , Amana Danielle , Boddaert Nathalie , Briault Sylvain , Bruel Ange-Line , Gitiaux Cyril , Kaminska Karolina , Philip-Sarles Nicole , Quinodoz Mathieu , Santos Cristina , Coutinho Santos Luisa , Sigaudy Sabine , Soeiro e Sá Mariana , Sousa Ana Berta , Thauvin Christel , Rivolta Carlo , Kaplan Josseline , Rozet Jean-Michel , Perrault Isabelle 
Published: August 2023

ABSTRACTSpliceosome and ciliary dysfunctions can lead to remarkably similar clinical syndromes. Studying ten individuals with retinal dystrophy, neurological involvement, and skeletal abnormalities, suggestive of both spliceosomopathies and ciliopathies, we involved GPATCH11, a lesser-known GPATCH-domain-containing regulators of RNA metabolism. To elucidate GPATCH11 function, we employed fibroblasts from unaffected individuals and patients carrying a recurring mutation specifically removing the main part of the GPATCH-domain while preserving other domains. Additionally, we generated a mouse model replicating the patient’s genetic defect, exhibiting behavioural abnormalities and retinal dystrophy. Our findings revealed GPATCH11 unique subcellular localization, marked as foci staining pattern and a diffuse presence in the nucleoplasm, alongside its centrosomal localization, indicating roles in RNA and cilia metabolism. We show dysregulation of U4 snRNA in patient cells and dysregulation in both gene expression and spliceosome activity within the mutant mouse retina, impacting key processes such as photoreceptor light responses, RNA regulation, and primary cilia-associated metabolism. These results highlight GPATCH11 roles in RNA metabolism, spliceosome regulation, and potential ciliary involvement. They underscore its significance in maintaining proper gene expression, contributing to retinal, neurological, and skeletal functions. Our research also demonstrates how studying rare genetic disorders can reveal broader gene functions, providing insights into GPATCH11 multifaceted roles.
JOINT CLINICAL AND MOLECULAR SUBTYPING OF COPD WITH VARIATIONAL AUTOENCODERS
Authors: Maiorino Enrico , De Marzio Margherita , Xu Zhonghui , Yun Jeong H. , Chase Robert P. , Hersh Craig P. , Weiss Scott T. , Silverman Edwin K. , Castaldi Peter J. , Glass Kimberly 
Published: August 2023

AbstractChronic Obstructive Pulmonary Disease (COPD) is a complex, heterogeneous disease. Traditional subtyping methods generally focus on either the clinical manifestations or the molecular endotypes of the disease, resulting in classifications that do not fully capture the disease’s complexity. Here, we bridge this gap by introducing a subtyping pipeline that integrates clinical and gene expression data with variational autoencoders. We apply this methodology to the COPDGene study, a large study of current and former smoking individuals with and without COPD. Our approach generates a set of vector embeddings, called Personalized Integrated Profiles (PIPs), that recapitulate the joint clinical and molecular state of the subjects in the study. Prediction experiments show that the PIPs have a predictive accuracy comparable to or better than other embedding approaches. Using trajectory learning approaches, we analyze the main trajectories of variation in the PIP space and identify five well-separated subtypes with distinct clinical phenotypes, expression signatures, and disease outcomes. Notably, these subtypes are more robust to data resampling compared to those identified using traditional clustering approaches. Overall, our findings provide new avenues to establish fine-grained associations between the clinical characteristics, molecular processes, and disease outcomes of COPD.
Validation of physical activity levels from shank-placed Axivity AX6 accelerometers
Authors: Gafoor Fatima , Ruder Matthew , Kobsar Dylan 
Published: August 2023

AbstractThis cross-sectional study aimed to identify and validate cut-points for measuring physical activity using Axivity AX6 accelerometers positioned at the shank in older adults. Free-living physical activity was assessed in 35 adults aged 55 and older, where each participant wore a shank mounted Axivity and a waist mounted ActiGraph simultaneously for 72 hours. Optimized cut-points for each participant’s Axivity data were determined using an optimization algorithm to align with ActiGraph results. To assess validity between the physical activity assessments from the optimized Axivity cut-points, a leave-one-out cross validation was conducted. Bland-Altman plots with 95% limits of agreement, intraclass correlation coefficients (ICC), and mean differences were used for comparing the systems. The results indicated good agreement between the two accelerometers when classifying sedentary behaviour (ICC = 0.85) and light physical activity (ICC = 0.80), and moderate agreement when classifying moderate physical activity (ICC = 0.67) and vigorous physical activity (ICC = 0.70). Upon removal of a significant outlier, the agreement was slightly improved for sedentary behaviour (ICC = 0.86) and light physical activity (ICC = 0.82), but substantially improved for moderate physical activity (ICC = 0.81) and vigorous physical activity (ICC = 0.96). Overall, the study successfully demonstrated the capability of the resultant cut-point model to accurately classify physical activity using Axivity AX6 sensors placed at the shank.
Individualized, self-supervised deep learning for blood glucose prediction
Authors: Fuest Johannes , Tacke Marco , Ullman Leander , Washington Peter 
Published: August 2023

AbstractThe current standard for monitoring blood glucose levels in diabetes patients are continuous glucose monitoring (CGM) devices, which are costly and carry the risk of complications, such as allergic reactions or skin irritations from the adhesive used to attach the CGM sensor to the skin. CGM devices are also highly visible and can thus act as a discomforting disease-marker for diabetes patients. To mitigate these issues, we develop and test a novel method that is able to predict blood glucose levels with only non-invasive predictor variables and a very small number of target variable measurements by using individualization and self-supervised deep learning. Using only a single blood glucose measurements per week, our method (6387.47 glucose-specific MSE) outperforms traditional deep learning performed with hourly measurements (8191.23 glucose-specific MSE). Across eight experiments where blood glucose measurements are more than one hour apart, our approach outperforms traditional deep learning without exception. Our findings suggest that self-supervised, individualized deep learning could provide an avenue towards alternatives to CGM devices that would be less costly, non-invasive, and thus more accessible.
Regulatory variation controlling architectural pleiotropy in maize
Authors: Bertolini Edoardo , Rice Brian R. , Braud Max , Yang Jiani , Hake Sarah , Strable Josh , Lipka Alexander E. , Eveland Andrea L. 
Published: August 2023

AbstractAn early event in plant organogenesis is establishment of a boundary between the meristem and differentiating lateral organ. In maize (Zea mays), evidence suggests a common gene network functions at boundaries of distinct organs and contributes to pleiotropy between leaf angle and tassel branch number, two agronomic traits. To uncover regulatory variation at the nexus of these two traits, we used regulatory network topologies derived from specific developmental contexts to guide multivariate genome-wide association analyses. In addition to defining network plasticity around core pleiotropic loci, we identified new transcription factors that contribute to phenotypic variation in canopy architecture, and structural variation that contributes tocis-regulatory control of pleiotropy between tassel branching and leaf angle across maize diversity. Results demonstrate the power of informing statistical genetics with context-specific developmental networks to pinpoint pleiotropic loci and theircis-regulatory components, which can be used to fine-tune plant architecture for crop improvement.
sRNAfrag: A pipeline and suite of tools to analyze fragmentation in small RNA sequencing data
Authors: Nakatsu Ken , Jijiwa Mayumi , Khadka Vedbar , Nasu Masaki , Huo Matthew , Deng Youping 
Published: August 2023

AbstractFragments derived from small RNAs such as small nucleolar RNAs hold biological relevance. However, they remain poorly understood, calling for more comprehensive methods for analysis. We developed sRNAfrag, a standardized workflow and set of scripts to quantify and analyze sRNA fragmentation of any biotype. In a benchmark, it is able to detect loci of mature microRNAs fragmented from precursors and, utilizing multi-mapping events, the conserved 5’ seed sequence of miRNAs which we believe may extraoplate to other small RNA fragments. The tool detected 1411 snoRNA fragment conservation events between 2/4 eukaryotic species, providing the opportunity to explore motifs and fragmentation patterns not only within species, but between. Availability:https://github.com/kenminsoo/sRNAfrag.
Cell-specific crosstalk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone
Authors: Norton Emily S. , Whaley Lauren A. , Jones Vanessa K. , Brooks Mieu M. , Russo Marissa N. , Morderer Dmytro , Jessen Erik , Schiapparelli Paula , Ramos-Fresnedo Andres , Zarco Natanael , Carrano Anna , Rossoll Wilfried , Asmann Yan W. , Lam TuKiet T. , Chaichana Kaisorn L. , Anastasiadis Panos Z. , Quiñones-Hinojosa Alfredo , Guerrero-Cázares Hugo 
Published: August 2023

SummaryGlioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially due to subventricular zone (SVZ) contact. Despite this, crosstalk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. Additionally, GBM brain tumor initiating cells (BTICs) increase expression of CTSB upon interaction with NPCs. Lentiviral knockdown and recombinant protein experiments reveal both cell-intrinsic and soluble CTSB promote malignancy-associated phenotypes in BTICs. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Finally, we show LV-proximal CTSB upregulation in patients, showing the relevance of this crosstalk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM.HighlightsPeriventricular GBM is more malignant and disrupts neurogenesis in a rodent model.Cell-specific proteomics elucidates tumor-promoting crosstalk between GBM and NPCs.NPCs induce upregulated CTSB expression in GBM, promoting tumor progression.GBM stalls neurogenesis and promotes NPC senescence via CTSB.
A high-resolution gene expression atlas of the medial and lateral domains of the gynoecium of Arabidopsis
Authors: Luna-García Valentín , Bernal Gallardo Judith Jazmin , Rethoret-Pasty Martin , Pasha Asher , Provart Nicholas J. , de Folter Stefan 
Published: August 2023

AbstractAngiosperms are characterized by the formation of flowers, and in their inner floral whorl, one or various gynoecia are produced. These female reproductive structures are responsible for fruit and seed production, thus ensuring the reproductive competence of angiosperms. InArabidopsis thaliana, the gynoecium is composed of two fused carpels with different tissues that need to develop and differentiate to consolidate a mature gynoecium and thus the reproductive competence of Arabidopsis. For these reasons, they have become the object of study for floral and fruit development. However, due to the complexity of the gynoecium, specific spatio-temporal tissues expression patterns are still scarce. In this study, we used precise laser-assisted microdissection and high-throughput RNA sequencing to describe the transcriptional profiles of the medial and lateral domain tissues of the Arabidopsis gynoecium. We provide evidence that the method used is reliable and that, in addition to corroborating gene expression patterns of previously reported regulators of these tissues, we found genes whose expression dynamics point to being involved in cytokinin and auxin homeostasis and in cell cycle progression. Furthermore, based on differential gene expression analyses, we functionally characterized several genes and found that they are involved in gynoecium development. This new resource is available via the Arabidopsis eFP browser and will serve the community in future studies on developmental and reproductive biology.
Evaluating public health effects of risk-based travel policy for the COVID-19 epidemic in Scotland
Authors: McLachlan Isobel , Huntley Selene , Leslie Kirstin , Bishop Jennifer , Redman Christopher , Yebra Gonzalo , Shaaban Sharif , Christofidis Nicolaos , Lycett Samantha , Holden Matthew T.G. , Robertson David L. , Smith-Palmer Alison , Hughes Joseph , Nickbakhsh Sema 
Published: August 2023

AbstractBackgroundDecisions to impose temporary travel measures are less common as the global epidemiology of COVID-19 evolves. Risk-based travel measures may avoid the need for a complete travel ban, however evaluations of their effects are lacking. Here we investigated the public health effects of a temporary traffic light system introduced in the United Kingdom (UK) in 2021, imposing red-amber-green (RAG) status based on risk assessment.MethodsWe analysed data on international flight passengers arriving into Scotland, COVID-19 testing surveillance, and SARS-CoV-2 whole genome sequences to quantify effects of the traffic light system on (i) international travel frequency, (ii) travel-related SARS-CoV-2 case importations, (iii) national SARS-CoV-2 case incidence, and (iv) importation of novel SARS-CoV-2 variants.ResultsInternational flight passengers arriving into Scotland had increased by 754% during the traffic light period. Amber list countries were the most frequently visited and ranked highly for SARS-CoV-2 importations and contribution to national case incidence. Rates of international travel and associated SARS-CoV-2 cases varied significantly across age, health board, and deprivation groups. Multivariable logistic regression revealed SARS-CoV-2 cases detections were less likely among travellers than non-travellers, although increasing from green-to-amber and amber-to-red lists. When examined according to travel destination, SARS-CoV-2 importation risks did not strictly follow RAG designations, and red lists did not prevent establishment of novel SARS-CoV-2 variants.ConclusionsOur findings suggest that country-specific post-arrival screening undertaken in Scotland did not prohibit the public health impact of COVID-19 in Scotland. Travel rates likely contributed to patterns of high SARS-CoV-2 case importation and population impact.
Incidence and Predictors of Neuropsychiatric manifestations following a Traumatic Brain Injury in Referral Hospitals in Dodoma, Tanzania: a protocol of a prospective longitudinal observational study
Authors: Aslan Suluma , Nyundo Azan 
Published: August 2023

ABSTRACTIntroductionTraumatic Brain Injury (TBI) is any injury to the brain resulting from an external force leading to complications. TBI affects 27-69 million yearly, with high incidence in Africa and LMICs, and is attributed to motor traffic accidents. Within three to six months following moderate-to-severe TBI, the relative risk of any psychiatric disorder is significantly higher than in the general population. Post-TBI neuropsychiatric disorders include; depression with a prevalence of over 50%, apathy up to 72%, Post-traumatic stress disorder (26%), anxiety (9%), manic symptoms (5 - 9%) and psychosis (3 to 8%).This study aims to determine the incidence and predictors of post-TBI neuropsychiatric manifestations among patients admitted at Referral hospitals in Dodoma.Methods and analysisThis is a prospective longitudinal observational study in which patients admitted after moderate to severe TBI will be recruited after obtaining informed consent. Patients will be followed for six months; the diagnostic MINI International Neuropsychiatric Interview (M.I.N.I) tool will assess psychiatric disorders, and severity and progression of symptoms will be assessed using PHQ-9 for depressive symptoms, GAD7 for anxiety symptoms, PCL-5 for Post-traumatic Stress Disorders (PTSD), MoCA for cognitive assessment, AES for apathy and YMRS for manic symptoms at one, three and six months. The analysis will use logistic regression to determine the association between predictors and neuropsychiatric outcomes.Ethics and disseminationThe ethical clearance has been secured from the institutional Research Review committee and ethical committee of the University of Dodoma with the reference number MA.84/261/12. The respective authorities provided permission to conduct the study within the premises of BMH and DRRH.Strength and limitationThe diagnostic tool “International Neuropsychiatric Interview (M.I.N.I),” is highly reliable and sensitive as it utilizes both DSM-5 and ICD-10 criteria, and screening tools there are used have good validity and reliability in assessing the severity progression of neuropsychiatric symptoms.The longitudinal prospective nature of the study offers a strong temporal association of the incidence, progression and associated factors of neuropsychiatric manifestations post-TBI.The study excluded patients with a known history of psychiatric diagnosis that could influence the recurrence relapse of the present illness and the existence of another new psychiatric diagnosis after TBI.