bluuebunny/crossref_metadata_2025_split huggingface dataset:
Root-specific activation of plasma membrane H+-ATPase 1 enhances plant growth and shoot accumulation of nutrient elements under nutrient-poor conditions in Arabidopsis thaliana
Authors: Monden Kota , Kamiya Takehiro , Sugiura Daisuke , Suzuki Takamasa , Nakagawa Tsuyoshi , Hachiya Takushi 
Published: May 2022

AbstractPlasma membrane (PM) H+-ATPase contributes to nutrient uptake and stomatal opening by creating proton gradient across the membrane. Previous studies report that a dominant mutation in the OPEN STOMATA2 locus (OST2-2D) constitutively activates Arabidopsis PM H+-ATPase 1 (AHA1), which enlarges proton motive force for root nutrient uptake. However, the stomatal opening is also constitutively enhanced in the ost2-2D, causing drought hypersensitivity. To develop plants with improved nutrient acquisition and normal stomatal movement, we generated grafted plants (scion/rootstock : Col-0 (WT)/ost2-2D), and compared their growth and nutrient element content with those of control plants (WT/WT) under two nutrient regimes. WT/ost2-2D shoots had larger weights, rosette diameter, leaf blade area, and content of C, N, K, Ca, S, P, Mg, Na, Mn, B, Co, and Mo under nutrient-poor conditions compared with WT/WT shoots. The root weights and primary root length were greater in WT/ost2-2D plants than in WT/WT plants under both nutrient conditions. These results suggest that root-specific activation of PM H+-ATPase enhances root nutrient uptake, which accelerates the plant growth under nutrient-poor condition. Our study presents a novel approach to improving nutrient uptake efficiency in crops and vegetable for the implementation of low-input sustainable agriculture.
Background noise in an Emergency Department: an observational study from staff and patient perspectives
Authors: Emar Murad , Smith Ella , Coats Timothy J 
Published: May 2022

AbstractBackground and importanceNoise is a contributing factor to mis-communication, poor sleep patterns and stress in healthcare. There has been little research on noise in the Emergency Department (ED).Objective(s)(1) To identify the noise levels experienced by staff and patients in different areas of an emergency department over the 24 hour cycle, (2) to examine the impact of cubicle doors on the background noise experienced by the patient, and (3) to assess the impact of monitor alarms on staff and patient noise levels.DesignObservational study.SettingA large urban teaching hospital Emergency Department.Measures and analysisUsing a standard protocol monitoring of staff and patient experience of noise was carried out in 3 areas of the ED (a resuscitation room, an area of patient cubicles with solid doors and and an area of patient cubicles with curtains).The overall distributions of noise levels in each area were described and circadian variation plotted. The proportion of time that background noise was above key cutoff values known to impair communication was calculated (45dB and 65dB).Non-parametric methods were used to compare: (1) a patient cubicle with curtains compared to a solid door, (2) having the door open or closed, and (3) staff and patient exposure a monitor alarm.Main resultsNoise was greater than 45dB for staff between 76% and 96% of the time (30% to 100% for patients). There was little difference across the 24hr cycle. A door decreased the noise experienced by patients, but only if left closed. In the resuscitation rooms monitor alarms were much louder for patients than for staff.ConclusionNoise levels likely to impair communication are present in the ED for most of the time. Staff awareness and improved design of both buildings and equipment might mitigate this negative acoustic environment.
Modelling the impact of combining HIV prevention interventions on HIV dynamics in fishing communities in Uganda
Authors: Kremer Cécile , Kamali Anatoli , Kuteesa Monica , Seeley Janet , Hens Niel , Nsubuga Rebecca N 
Published: May 2022

AbstractBackgroundIn countries with mature generalized HIV epidemics such as Uganda, there are still groups of individuals that are disproportionately affected. These most at risk populations (MARPs) have high HIV prevalence compared to the general population. Among the MARPs in Uganda are fishing communities, which make up about 10% of the population.MethodsWe investigated the impact of combined HIV prevention interventions on HIV transmission dynamics in high-risk fishing communities in Uganda using a deterministic compartmental model. The model was calibrated to seroprevalence data from a census performed in 2014. To account for remaining uncertainty in the calibrated model parameters, an additional 50 000 simulated scenarios were modelled to investigate the impact of combined interventions.ResultsThe projected HIV incidence decreased from 1.87 per 100 PY without intervention scale-up to 0.25 per 100 PY after 15 years (2014-2029) of intervention scale-up. A potential combination achieving this 87% reduction in incidence included condom use in about 60% of sexual acts, 23% of susceptible men circumcised, 87% of people living with HIV aware of their status, 75% of those on ART, and about 3% of susceptible individuals on oral PrEP. Uncertainty analysis revealed relative reductions in incidence ranging from 30.9% to 86.8%. Sensitivity analyses suggested that condom use and early ART were the most important intervention components.ConclusionsReducing HIV incidence, and consequently prevalence and AIDS-related mortality, in these high-risk fishing communities in Uganda is attainable in the long-run with a combination prevention package. Our projected intervention coverage levels are well within the national targets set by the Uganda government and close to reaching the UNAIDS 95-95-95 goal to end AIDS by 2030.
Assessing the knowledge and practices of primary healthcare workers on malaria diagnosis and related challenges in view of COVID-19 outbreak in a Nigerian Southwestern Metropolis
Authors: Ayandipo Esther , Babatunde Deborah , Afolayan Oladipo , Kalejaye Olabisi , Obembe Taiwo 
Published: May 2022

AbstractBackgroundThe clinical features of COVID-19 and malaria are interrelated. Due to the similarity of symptoms between the two disease states, patients can be incorrectly diagnosed with the other ailment in areas with limited health resources. There is a dearth of knowledge of co-infection between COVID-19 and malaria from healthcare providers’ perspective. Hence, this study assessed the ability of primary healthcare workers to diagnose malaria infection correctly from COVID-19 infection.MethodsA multistage sampling technique was used to select health care workers who were directly involved in malaria case management at 261 government-owned primary health facilities in Oyo State. Socio-demographic characteristics of respondents, knowledge & practices, COVID-19 differential diagnosis and challenges that healthcare workers face regarding malaria diagnosis were obtained using a standardized electronic structured questionnaire. Descriptive statistics, bivariate and multivariate analysis were conducted on data collected and significant results were interpreted at a 5% level of significance.ResultsA good percentage of the respondents (81.6%, 74.3%) had good knowledge about malaria and COVID-19 infection. However, the knowledge gained did not translate to practice, as majority (86.2%) of respondents had poor malaria diagnosis practices. Practices relating to COVID-19 differential diagnosis in 69.7% of respondents were also poor. Most of the respondents attributed poor practices to the unavailability of Malaria Rapid Diagnostic Test (mRDT), inadequate training and continuous capacity improvement. Only 12.3% of the respondents had any form of training on malaria diagnosis and treatment in the last five years.ConclusionHarmonization of regular trainings and continuous on-the job capacity building is essential to improve case identification, diagnosis and management of both ailments. Also, uninterrupted supplies of essential commodities such as mRDT in laboratories will reduce missed opportunities for malaria diagnosis.
Sex differences in depression and sleep disturbance as inter-related risk factors of diabetes
Authors: Li Clara S. , Porta Rose , Chaudhary Shefali 
Published: May 2022

ABSTRACTBackgroundPrevious studies identified depression and sleep disturbance as risk factors for diabetes. Sleep disturbance and depression are known to be inter-related. Further, women relative to men are more prone to depression. Here, we investigated how depression and sleep disturbance may jointly influence the risk of diabetes and the effects of sex on these influences.MethodsUsing the data of 21,229 participants from the 2018 National Health Interview Survey, we performed multivariate logistic regression with diabetes diagnosis as the dependent variable, sex, self-reported frequency of weekly depression and nightly sleep duration, and their interactions with sex as independent variables, and age, race, income, body mass index and physical activity as covariates. We employed Bayesian and Akaike Information criteria to identify the best model, evaluated the accuracy of the model in predicting diabetes using receiver operating characteristic analysis, and computed the odds ratios of these risk factors.ResultsIn the two best models, depression frequency and sleep hours interact with sex in determining the diagnosis of diabetes, with higher depression frequency and nightly duration of sleep longer or shorter than 7 to 8 hours associated with higher likelihood of diabetes. The two models both predicted diabetes at an accuracy (area under the receiver operating characteristic curve) of 0.86. Further, these effects were stronger in men than in women at each depression and sleep level.ConclusionsDepression and sleep inter-relatedly rather than independently contributes to diabetes. Depression and sleep hours associate with diabetes more significantly in men than in women. The current findings indicate a sex-dependent relationship between depression, sleep disturbance and diabetes risk and add to a growing body of evidence linking mental and physical health.
PGC-1β and ERRα promote glutamine metabolism and colorectal cancer survival via transcriptional regulation of PCK2
Authors: Frodyma Danielle E. , Troia Thomas C. , Rao Chaitra , Svoboda Robert A. , Berg Jordan A. , Shinde Dhananjay D. , C.Thomas Vinai , Lewis Robert E. , Fisher Kurt W. 
Published: May 2022

AbstractPrevious studies have shown that Peroxisome Proliferator-Activated Receptor Gamma, Coactivator 1 Beta (PGC-1β) and Estrogen-Related Receptor Alpha (ERRα) are over-expressed in colorectal cancer and promote tumor survival. In this study, we show that amino acid motif LRELL on PGC-1β is responsible for the physical interaction with ERRα and promotes ERRα mRNA and protein expression. We used RNAsequencing to determine the genes regulated by both PGC-1β & ERRα and found that mitochondrial Phosphoenolpyruvate Carboxykinase 2 (PCK2) was the gene that decreased most significantly after depletion of both genes. Depletion of PCK2 in colorectal cancer cells was sufficient to reduce anchorage-independent growth and inhibit glutamine utilization by the TCA cycle. Lastly, shRNA-mediated depletion of ERRα decreased anchorage-independent growth and glutamine metabolism, which could not be rescued by plasmid derived expression of PCK2. These findings suggest that transcriptional control of PCK2 is one mechanism used by PGC-1β and ERRα to promote glutamine metabolism and colorectal cancer cell survival.
Human primed and naïve PSCs are both competent in differentiating into bona fide trophoblast stem cells
Authors: Viukov Sergey , Shani Tom , Bayerl Jonathan , Sheban Daoud , Stelzer Yonatan , Novershtern Noa , Hanna Jacob 
Published: May 2022

SummaryCells of the trophoblast lineage constitute the major part of placental tissues in higher mammals. Recent derivation of human trophoblast stem cells (TSC) from placental cytotrophoblasts (CT) and from human naïve PSCs opens new opportunities for studying development and function of human placenta. Several recent reports have suggested that naïve human PSCs retain an exclusive potential to give rise to bona fide TSCs. Here we report that inhibition of TGFβ pathway and avoiding WNT stimulation, leads to direct and robust conversion of primed human pluripotent stem cells into TSCs. Systematic side by side comparative analysis showed that the latter are equivalent to previously derived TSC lines. Primed PSC derived TSC lines exhibit self-renewal, are able to differentiate into the main trophoblast lineages, and present RNA and epigenetic profiles that are indistinguishable from the TSC lines derived from placenta or naïve PSCs. Our findings underscore a residual plasticity in primed human PSCs that allows converting directly into pre-implantation extra-embryonic cell lineages.HighlightsPrimed human PSCs readily convert into TSCs upon inhibition of TGF pathwayCHIR inhibits conversion to TSC in primed but not in naive hPSCsPrimed human PSC derived TSCs line are indistinguishable from placental and naïve derived TSCsYAP is sufficient for TSC induction from hPSCs and necessary for TSC maintenance.
Complexity of enhancer networks predicts cell identity and disease genes revealed by single-cell multi-omics analysis
Authors: Hong Danni , Lin Hongli , Liu Lifang , Shu Muya , Dai Jianwu , Lu Falong , Tong Mengsha , Huang Jialiang 
Published: May 2022

AbstractMany enhancers exist as clusters in the genome and control cell identity and disease genes; however, the underlying mechanism remains largely unknown. Here, we introduce an algorithm, eNet, to build enhancer networks by integrating single-cell chromatin accessibility and gene expression profiles. Enhancer network is a gene regulation model we proposed that not only delineates the mapping between enhancers and target genes, but also quantifies the underlying regulatory relationships among enhancers. The complexity of enhancer networks is assessed by two metrics: the number of enhancers and the frequency of predicted enhancer interactions (PEIs) based on chromatin co-accessibility. We apply eNet algorithm to a human blood dataset and find cell identity and disease genes tend to be regulated by complex enhancer networks. The network hub enhancers (enhancers with frequent PEIs) are the most functionally important in enhancer networks. Compared with super-enhancers, enhancer networks show better performance in predicting cell identity and disease genes. The establishment of enhancer networks drives gene expression during lineage commitment. Applying eNet in various datasets in human or mouse tissues across different single-cell platforms, we demonstrate eNet is robust and widely applicable. Thus, we propose a model of enhancer networks containing three modes: Simple, Multiple and Complex, which are distinguished by their complexity in regulating gene expression.Taken together, our work provides an unsupervised approach to simultaneously identify key cell identity and disease genes and explore the underlying regulatory relationships among enhancers in single cells, without requiring the cell type identity in advance.HighlightseNet, a computational method to build enhancer network based on scATAC-seq and scRNA-seq dataCell identity and disease genes tend to be regulated by complex enhancer networks, where network hub enhancers are functionally importantEnhancer network outperforms the existing models in predicting cell identity and disease genes, such as super-enhancer and enhancer clusterWe propose a model of enhancer networks in gene regulation containing three modes: Simple, Multiple and Complex
Humanized CAR T cells targeting p95HER2
Authors: Román Macarena , Rius-Ruiz Irene , Grinyó-Escuer Ariadna , Duro-Sánchez Santiago , Escorihuela Marta , Moessner Ekkehard , Klein Christian , Arribas Joaquín 
Published: May 2022

AbstractRedirection of T lymphocytes against tumor-associated or tumor-specific antigens, via bispecifc T cells engagers (BiTEs) or chimeric antigen receptors (CARs), is a successful therapeutic strategy against certain hematologic malignancies. In contrast, so far it has failed against solid tumors. Given the scarcity of tumor-specific antigens, the vast majority of BiTEs and CAR Ts developed to date have been directed against tumor-associated antigens. These are expressed in some normal tissues and, as a consequence, frequent and serious side effects caused by on-target off-tumor activity have limited the use of BiTEs and CARs in the clinic. P95HER2 is a fragment of the tyrosine kinase receptor HER2 expressed in more than 30% of HER2-amplified tumors. It has been previoulsy shown that p95HER2 is a tumor-specific antigen. Here we present the generation of CARs targeting p95HER2. p95HER2 CAR T cells show remarkable activity against p95HER2-expressing cells in vitro and in vivo. Further, they are also effective against lung and brain metastasis. These tumor-specific CAR T cells could be used in the near future to deliver additional anti-tumor therapies in a safe manner.
Spurious intragenic transcription is a hallmark of mammalian cellular senescence and tissue aging
Authors: Sen P. , Donahue G. , Li C. , Lan Y. , Egervari G. , Robertson N. , Shah P. P. , Kerkhoven E. , Schultz D. C. , Adams P. D. , Berger S. L. 
Published: May 2022

AbstractMammalian aging is characterized by the progressive loss of tissue integrity and function manifesting in ill health and increased risk for developing multiple chronic conditions. Accumulation of senescent cells in aging tissues partly contributes to this decline and targeted depletion of senescent cells in vivo ameliorates many age-related phenotypes. However, the fundamental molecular mechanisms responsible for the decline of cellular health and fitness during senescence and aging are largely unknown. In this study, we investigated whether chromatin-mediated loss of transcriptional fidelity, known to contribute to fitness and survival in yeast and worms, also occurs during human cellular senescence and mouse aging. Our findings reveal that aberrant transcription initiation inside genes is widespread in senescence and aging. It co-occurs with changes in the chromatin landscape and formation of non-canonical transcription start sites. Interventions that alter spurious transcripts have dramatic consequences on cellular health primarily affecting intracellular signal transduction pathways. We propose that spurious transcription is a conserved hallmark of aging that promotes a noisy transcriptome and degradation of coherent transcriptional networks.
Genome-wide association mapping reveals genes underlying population-level metabolome diversity in a fungal crop pathogen
Authors: Singh Nikhil Kumar , Tralamazza Sabina Moser , Abraham Leen Nanchira , Glauser Gaétan , Croll Daniel 
Published: May 2022

AbstractBackgroundFungi produce a wide range of specialized metabolites (SMs) involved in biotic interactions. Pathways for the production of SMs are often encoded in clusters of tightly arranged genes identified as biosynthetic gene clusters. Such gene clusters can undergo horizontal gene transfers between species and rapid evolutionary change within species. The acquisition, rearrangement and deletion of gene clusters can generate significant metabolome diversity. However, the genetic basis underlying variation in SM production remains poorly understood.ResultsHere, we analyzed metabolite production of a large population of the fungal pathogen of wheat, Zymoseptoria tritici. The pathogen causes major yield losses and shows variation in gene clusters. We performed untargeted ultra-high performance liquid chromatography-high resolution mass spectrometry to profile the metabolite diversity among 102 isolates of the same species. We found substantial variation in the abundance of the detected metabolites among isolates. Integrating whole-genome sequencing data, we performed metabolite genome-wide association mapping to identify loci underlying variation in metabolite production (i.e. metabolite-GWAS). We found that significantly associated SNP reside mostly in coding and gene regulatory regions. Associated genes encode mainly transport and catalytic activities. The metabolite-GWAS identified also a polymorphism in the 3’UTR region of a virulence gene related to metabolite production and showing expression variation.ConclusionsTaken together, our study provides a significant resource to unravel polymorphism underlying metabolome diversity within a species. Integrating metabolome screens should be feasible for a range of different plant pathogens and help prioritize molecular studies.
Differences in Gut Microbiota Assembly Alter Its Ability to Metabolize Dietary Polysaccharides and Resist Clostridioides difficile Colonization
Authors: Schnizlein Matthew K. , Standke Alexandra K. , Garmo Mark J. , Edwards Summer J. , Young Vincent B. 
Published: May 2022

AbstractThe mammalian gut is home to a vibrant community of microbes. As the gut microbiota has evolved, its members have formed a complex yet stable relationships that prevent non-indigenous microorganisms, such as Clostridioides difficile, from establishing within the gut. Using a bioreactor model of the gut, we characterize how variation in microbial community assembly changes its ability to resist C. difficile. We established diluted microbial communities from healthy human stool in a bioreactor gut model and subsequently challenged them with vegetative C. difficile. 16S rRNA-gene sequencing and selective plating revealed that dilution progressively increases microbiota variability and decreases C. difficile colonization resistance. Using Dirichlet Multinomial Mixtures and linear discriminant analysis of effect size, we identified 19 bacterial taxa, including Bifidobacterium, Bacteroides and Lachnospiraceae, that associate with more resistant community types. Since these taxa are associated with butyrate production, which is tied to C. difficile colonization resistance, we performed another reactor experiment where we increased inulin concentrations prior to C. difficile challenge. Diluted communities concurrently lost their ability to produce additional butyrate in response to inulin, as measured by high performance liquid chromatography, and resist C. difficile colonization. These data demonstrate that a similar level of microbiota cohesiveness is required to prevent C. difficile colonization and metabolize inulin. It also suggests that metabolic activity of butyrate-producing microbes is tied to colonization resistance. Future work can leverage these findings to develop treatments that leverage knowledge of these ecological dynamics to improve efficacy.ImportanceThe microbes living in the human large intestine helps create an environment that is resistant to organisms that do not normally reside there, such as the pathogen Clostridioides difficile. Differences in ways in which microbial communities make an environment their home can change their ability to provide that resistance. To study those differences, we use a model of the intestine that incorporates only microbial variables (i.e. no host is involved). By diluting microbial communities to decrease their complexity, we show that communities lose their ability to resist C. difficile at a particular point and, at the same time, their ability to use inulin, a common dietary fiber, in ways that make the environment more toxic to C. difficile. These findings will help future researchers dissect the microbial components that create a resistant intestinal environment.