bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoscale resolution of microbial fiber degradation in action
Authors: Tatlı Meltem , Moraïs Sarah , Tovar-Herrera Omar E. , Bomble Yannick , Bayer Edward A. , Medalia Ohad , Mizrahi Itzhak 
Published: February 2021

AbstractDeconstruction of plant cell walls is imperative to global carbon cycling and sustainability efforts. Selected microbes degrade plant fibers using extremely efficient multi-enzymatic cellulosomes assemblies. Organization of cellulosomes on the bacterial cell surface and their ecological regulation remain elusive. By combining structural methodologies with molecular and biochemical approaches on the canonicalClostridium thermocellumsystem, we provide an unprecedented view into the in-situ structure and distribution of cellulosomal enzymes while interacting with their cellulosic substrate during fiber degradation. Structural exploration of growing cultures revealed isogenic phenotypic heterogeneity of cellulosome organization on single cells across the bacterial population, suggesting a division-of labor strategy driven by product-dependent dynamics. This study demonstrates how structural biology under near-physiological conditions can be employed to develop ecological hypotheses to understand microbial plant-fiber degradation at the single-cell nanoscale level.One Sentence SummaryThis study contributes critical insights into thein-situorganization of cellulosomes and their cellulosic substrates and provides evidence for phenotypic heterogeneity, with dynamic, growth phase-dependent organization of the fiber-degrading machinery.
Parallel processing of working memory and temporal information by distinct types of cortical projection neurons
Authors: Bae Jung Won , Jeong Huijeong , Bae Chanmee , Lee Hyeonsu , Paik Se-Bum , Jung Min Whan 
Published: February 2021

AbstractIt is unclear how different types of cortical projection neurons work together to support diverse cortical functions. We examined the discharge characteristics and inactivation effects of intratelencephalic (IT) and pyramidal tract (PT) neurons—two major types of cortical excitatory neurons that project to cortical and subcortical structures, respectively—in the medial prefrontal cortex of mice performing a delayed response task. We found that IT neurons, but not PT neurons, convey significant working memory-related signals. We also found that the inactivation of IT neurons, but not PT neurons, impairs behavioral performance. In contrast, PT neurons convey far more temporal information than IT neurons during the delay period. Our results indicate a division of labor between IT and PT projection neurons in the prefrontal cortex for the maintenance of working memory and for tracking the passage of time, respectively.
Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells
Authors: Vasseur Maxence Le , Friedman Jonathan R. , Jost Marco , Xu Jiawei , Yamada Justin , Kampmann Martin , Horlbeck Max A. , Salemi Michelle R. , Phinney Brett S. , Weissman Jonathan S. , Nunnari Jodi 
Published: February 2021

AbstractDysfunction of the mitochondrial electron transport chain (mETC) is a major cause of human mitochondrial diseases. To identify determinants of mETC function, we screened a genome-wide human CRISPRi library under oxidative metabolic conditions with selective inhibition of mitochondrial Complex III and identified OCIA domain-containing protein 1 (OCIAD1) as a Complex III assembly factor. We find that OCIAD1 is an inner mitochondrial membrane protein that forms a complex with supramolecular prohibitin assemblies. Our data indicate that OCIAD1 is required for maintenance of normal steady state levels of Complex III and the proteolytic processing of the catalytic subunit cytochromec1(CYC1). In OCIAD1 depleted mitochondria, unprocessed CYC1 is hemylated and incorporated into Complex III. We propose that OCIAD1 acts as an adaptor within prohibitin assemblies to stabilize and/or chaperone CYC1 and to facilitate its proteolytic processing by the IMMP2L protease.
IRONMAN Tunes Responses to Iron Deficiency in Concert with Environmental pH
Authors: Gautam Chandan Kumar , Tsai Huei-Hsuan , Schmidt Wolfgang 
Published: February 2021

ABSTRACTIron (Fe) is an essential mineral element which governs the composition of natural plant communities and limits crop yield in agricultural ecosystems due to its extremely low availability in most soils, particularly at alkaline pH. To extract sufficient Fe from the soil under such conditions, some plants includingArabidopsis thalianasecrete Fe-mobilizing phenylpropanoids, which mobilize sparingly soluble Fe hydroxides by reduction and chelation. We show here that ectopic expression of theIRONMANpeptidesIMA1andIMA2improves growth on calcareous soil by inducing the biosynthesis and secretion of the catecholic coumarin fraxetin (7,8-dihydroxy-6-methoxycoumarin) through increased expression ofMYB72andSCOPOLETIN 8-HYDROXYLASE(S8H), a response which is strictly dependent on elevated environmental pH (pHe). By contrast, transcription of the cytochrome P450 family proteinCYP82C4,catalyzing the subsequent hydroxylation of fraxetin to sideretin, which forms less stable complexes with iron, was strongly repressed under such conditions. Luciferase reporter assays in transiently transformed protoplasts showed that IMA1/IMA2 peptides are translated and modulate the expression ofCYP82C4andMYB72by acting as transcriptional coactivators. It is concluded that IMA peptides regulate processes supporting Fe uptake at both acidic and elevated pH by controlling gene expression upstream of or in concert with a putative pHesignal to adapt the plant to the prevailing edaphic conditions. This regulatory pattern confers tolerance to calcareous soils by extending the pH range in which Fe can be efficiently absorbed from the soil. Altering the expression of IMA peptides provides a novel route for generating plants adapted to calcareous soils.One sentence summaryEctopic expression of IRONMAN peptides improves growth under iron-limiting conditions by inducing responses to limited iron availability in accordance with the environmental pH.The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantphysiol.org) is: Wolfgang Schmidt (wosh@gate.sinica.edu.tw).
The neural G protein Gαotagged with GFP at an internal loop is functional inC. elegans
Authors: Kumar Santosh , Olson Andrew C. , Koelle Michael R. 
Published: February 2021

AbstractGαois the alpha subunit of the major heterotrimeric G protein in neurons and mediates signaling by every known neurotransmitter, yet the signaling mechanisms activated by Gαoremain to be fully elucidated. Genetic analysis inCaenorhabditis eleganshas shown that Gαosignaling inhibits neuronal activity and neurotransmitter release, but studies of the molecular mechanisms underlying these effects have been limited by lack of tools to complement genetic studies with other experimental approaches. Here we demonstrate that inserting the green fluorescent protein (GFP) into an internal loop of the Gαoprotein results in a tagged protein that is functionalin vivoand that facilitates cell biological and biochemical studies of Gαo. Transgenic expression of Gαo-GFP rescues the defects caused by loss of endogenous Gαoin assays of egg laying and locomotion behaviors. Defects in body morphology caused by loss of Gαoare also rescued by Gαo-GFP. The Gαo-GFP protein is localized to the plasma membrane of neurons, mimicking localization of endogenous Gαo. Using GFP as an epitope tag, Gαo-GFP can be immunoprecipitated fromC. eleganslysates to purify Gαoprotein complexes. The Gαo-GFP transgene reported in this study enables studies involvingin vivolocalization and biochemical purification of Gαoto complement the already well-developed genetic analysis of Gαosignaling.
Deep Behavioral Phenotyping of Mouse Autism Models using Open-Field Behavior
Authors: Klibaite Ugne , Kislin Mikhail , Verpeut Jessica L. , Sun Xiaoting , Shaevitz Joshua W. , Wang Samuel S.-H. 
Published: February 2021

AbstractAutism is noted for both its genotypic and phenotypic diversity. Repetitive action, resistance to environmental change, and motor disruptions vary from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we use advances in computer vision and deep learning to develop a framework for characterizing mouse behavior on multiple time scales using a single popular behavioral assay, the open field test. We observed male and female C57BL/6J mice to develop a dynamic baseline of adaptive behavior over multiple days. We then examined two rodent models of autism, a cerebellum-specific model, L7-Tsc1, and a whole-brain knockout model, Cntnap2. Both Cntnap2 knockout and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure-to-adapt took the form of maintained ambling, turning, and locomotion, and an overall decrease in grooming. Adaptation in Cntnap2 knockout mice more broadly resembled that of wild-type. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy. Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics.
Molecular origin of somatostatin-positive neuron vulnerability
Authors: Tomoda Toshifumi , Sumitomo Akiko , Newton Dwight , Sibille Etienne 
Published: February 2021

AbstractReduced somatostatin (SST) and SST-positive (SST+) neurons are hallmarks of neurological disorders and associated with mood disturbances, but their origin are unknown. Chronic psychosocial stress induces behavioral emotionality deficits and deregulates unfolded protein response (UPR) of the endoplasmic reticulum (ER) preferentially in SST+neurons. Here we confirm that chronic stress increases ER stress levels in SST+neurons of mouse prefrontal cortex, and show that genetically suppressing ER stress in SST+neurons, but not in pyramidal neurons, normalized psychosocial stress-induced behavioral emotionality. Forced expression of SST precursor protein (preproSST), mimicking psychosocial stress-induced early proteomic changes, induces ER stress, whereas mature SST or processing-incompetent preproSST does not. Biochemical analyses further show that psychosocial stress induces SST protein aggregation under elevated ER stress conditions. These results demonstrate that SST processing is a SST+neuron-intrinsic vulnerability factor under conditions of sustained or over-activated UPR in the ER, hence negatively impacting SST+neuron functions.
E484K mutation in SARS-CoV-2 RBD enhances binding affinity with hACE2 but reduces interactions with neutralizing antibodies and nanobodies: Binding free energy calculation studies
Authors: Wang Wei Bu , Liang Yu , Jin Yu Qin , Zhang Jing , Su Ji Guo , Li Qi Ming 
Published: February 2021

AbstractThe pandemic of the COVID-19 disease caused by SARS-CoV-2 has led to more than 100 million infections and over 2 million deaths worldwide. The progress in the developments of effective vaccines and neutralizing antibody therapeutics brings hopes to eliminate the threat of COVID-19. However, SARS-CoV-2 continues to mutate, and several new variants have been emerged. Among the various naturally-occurring mutations, the E484K mutation shared by both the 501Y.V2 and 501Y.V3 variants attracted serious concerns, which may potentially enhance the receptor binding affinity and reduce the immune response. In the present study, the molecular mechanism behind the impacts of E484K mutation on the binding affinity of the receptor-binding domain (RBD) with the receptor human angiotensin-converting enzyme 2 (hACE2) was investigated by using the molecular dynamics (MD) simulations combined with the molecular mechanics-generalized Born surface area (MMGBSA) method. Our results indicate that the E484K mutation results in more favorable electrostatic interactions compensating the burial of the charged and polar groups upon the binding of RBD with hACE2, which significantly improves the RBD-hACE2 binding affinity. Besides that, the E484K mutation also causes the conformational rearrangements of the loop region containing the mutant residue, which leads to more tight binding interface of RBD with hACE2 and formation of some new hydrogen bonds. The more tight binding interface and the new hydrogen bonds formation also contribute to the improved binding affinity of RBD to the receptor hACE2. In addition, six neutralizing antibodies and nanobodies complexed with RBD were selected to explore the effects of E484K mutation on the recognition of these antibodies to RBD. The simulation results show that the E484K mutation significantly reduces the binding affinities to RBD for most of the studied neutralizing antibodies, and the decrease in the binding affinities is mainly owing to the unfavorable electrostatic interactions caused by the mutation. Our studies revealed that the E484K mutation may improve the binding affinity between RBD and the receptor hACE2, implying more transmissibility of the E484K-containing variants, and weaken the binding affinities between RBD and the studied neutralizing antibodies, indicating reduced effectiveness of these antibodies. Our results provide valuable information for the effective vaccine development and antibody drugs design.
A measles-vectored COVID-19 vaccine induces long-term immunity and protection from SARS-CoV-2 challenge in mice
Authors: Frantz Phanramphoei N. , Barinov Aleksandr , Ruffié Claude , Combredet Chantal , Najburg Valérie , Teeravechyan Samaporn , Jongkaewwattana Anan , Prot Matthieu , Conquet Laurine , Montagutelli Xavier , Fernandes Priyanka , Strick-Marchand Hélène , Di Santo James , Simon-Lorière Etienne , Gerke Christiane , Tangy Frédéric 
Published: February 2021

AbstractIn light of the expanding SARS-CoV-2 pandemic, developing efficient vaccines that can provide sufficient coverage for the world population is a global health priority. The measles virus (MV)-vectored vaccine is an attractive candidate given the measles vaccine’s extensive safety history, well-established manufacturing process, and induction of strong, long-lasting immunity. We developed an MV-based SARS-CoV-2 vaccine using either the full-length spike (S) or S2 subunit as the antigen. While the S2 antigen failed to induce neutralizing antibodies, the prefusion-stabilized, full-length S (MV-ATU2-SF-2P-dER) construct proved to be an attractive vaccine candidate, eliciting strong Th1-dominant T-cell and neutralizing antibody responses against the S antigen while minimizing reactivity to the vector itself. Neutralizing antibody titers remained high three months after homologous prime-boost immunization, and infectious virus was undetectable in all animals after challenge with a mouse-adapted SARS-CoV-2 virus.
Dynamic conceptual framework to investigate adoption of healthy diet through agent-based modelling
Authors: Rahmani Jamal , Mirzay Razaz Jalaledin , Kalantari Naser , Garcia Leandro M.T. , Shariatpanahi Seyed Peyman , Bawadi Hiba , Thompson Jacqueline Y. , Ryan Paul M. , Santos Heitor O. , Haghighian Roudsari Arezoo 
Published: February 2021

PurposeThe purpose of this research is to develop a dynamic conceptual framework depicting factors related to the adoption of a healthy diet, which will underpin the development of an agent-based model (ABM) to uncover the dynamic interplay between these factors.Design/methodology/approachThe conceptual framework was developed in three steps using available empirical data from a semi-structured in-depth interview qualitative study, comprehensive systematic literature searches, existing theories and models and expert opinions from across the world.FindingsThe conceptual framework explicitly presents intention as the key determinant of the tendency to adopt a healthy diet. Intention is determined by demographic, psychological and behavioural factors and individual dietary mindset factors and dynamically affected by social environment and the person's past behaviour. The relationship between intention and behaviour is dynamically moderated by perceived control factors (price and accessibility of healthy food and time).Originality/valueThe conceptual framework developed in this study is well supported by evidence and experts' opinions. This conceptual framework will be used to design the ABM of this study, and it can be used in future investigations on the tendency to adopt healthy diet and food choices.
Housing market networks in China's major cities: a conditional causality approach
Authors: Yang Lu , Yuan Nannan , Hu Shichao 
Published: February 2021

PurposeTo explore the state of this conditional Granger causality when other cities are not factors, we investigate housing market networks in China's major cities by using a combination of conditional Granger causality and network analysis.Design/methodology/approachAlthough housing market networks have been well discussed for different countries, the question of housing market networks in China's major cities based on the conditional causality perspective has yet to be answered.FindingsWe discover that second-tier cities are more influential than first-tier cities. Although the connectivity of the primary housing market is more complex than the diversified connectivity observed in the secondary housing market, both markets are scale-free networks that exhibit high stability. Moreover, we reveal that geographic conditions and economic development jointly determine the housing market's modular hierarchical structure. Our results provide meaningful information for both Chinese policymakers and investors.Originality/valueBy excluding the influence of other cities, our conditional Granger causality identifies the true casual relation between cities' housing markets. Moreover, it is the first paper to consider the primary housing market and secondary housing market separately. Specifically, Chinese prefer new house rather than second-hand house from both speculative and self-housing. Generally speaking, the new house price is lower than the second-hand house price since the new house is off-plan property. Therefore, understanding the difference between primary and secondary housing markets will provide useful information for both policymakers and speculators.
Factors predicting six-month exclusive breastfeeding among mothers in Ho Chi Minh City, Vietnam
Authors: Nguyen Nhan Thi , Prasopkittikun Tassanee , Payakkaraung Sudaporn , Vongsirimas Nopporn 
Published: February 2021

PurposeExclusive breastfeeding (EBF) rates continue to be low in Vietnam. This study aimed to determine the factors predicting 6-month EBF among mothers in Ho Chi Minh City, Vietnam.Design/methodology/approachA cross-sectional study was conducted with 259 mothers of infants aged between six to nine months at well-baby clinics in Ho Chi Minh City. The questionnaires used for data collection included personal background questionnaire, perceived benefits of breastfeeding scale, breastfeeding self-efficacy scale-short form, perceived barriers to breastfeeding scale and the family support of breastfeeding scale. Descriptive statistics, bivariate and multiple logistic regression were used for data analysis.FindingsAbout 32% of the Vietnamese mothers practiced 6-month EBF. By increasing one unit of perceived benefits of breastfeeding, perceived self-efficacy in breastfeeding and family support, the mothers' likelihood to give 6-month EBF would increase 19% (AOR = 1.19, 95% CI = 1.08, 1.31), 12% (AOR = 1.12, 95% CI = 1.04, 1.19) and 10% (AOR = 1.10, 95% CI = 1.04, 1.16), while previous breastfeeding experience, maternal age and maternal education could not significantly contribute to the 6-month EBF.Originality/valueThis is the first study in Vietnam using a nursing model, the health promotion model, as a framework to identify factors predicting 6-month EBF. An effective program for promoting EBF could be developed by manipulating and tailoring the predicting factors to fit the Vietnamese mothers' needs through a mother class, lactation clinic or individual approach.
Evidence to Support the Clinical Utility of Prenatal Exome Sequencing in Evaluation of the Fetus with Congenital Anomalies
Authors: Mone F , McMullan DJ , Williams D , Chitty LS , Maher ER , Kilby MD ,   Fetal Genomics Steering Group of the British Society for Genetic Medicine,   the Royal College of Obstetricians and Gynaecologists
Published: February 2021

Plain language summaryStructural differences (congenital anomalies) in the makeup of the baby's heart, brain and other organs are found on antenatal ultrasound scans in up to 3% of pregnancies. These often have a genetic cause, arising because of changes in the chromosomes (which store our genetic material) or the DNA code that make up the genes. The more differences a baby has the more likely the risk of underlying genetic disease. If a structural difference is found, parents are usually offered a genetic test, which may be carried out on cells taken either from the placenta (chorionic villous sampling) or the fluid surrounding the baby (amniocentesis). At the moment, these cells are only tested for changes in the chromosomes and are only able to reveal the underlying cause in about 40% of unborn babies.Prenatal exome sequencing (ES) is a new genetic test, which, when combined with testing the DNA of both parents can find changes in the baby's genetic code. If a DNA change is found that can explain the structural changes seen on ultrasound, specific information about the underlying diagnosis can be given to the parents. Having this information can help parents make important decisions about their ongoing pregnancy, as well as help doctors to care for the mother and baby. Finding a genetic change can also help to understand how the condition has arisen and whether it might happen again in another pregnancy. It may also be possible to test for the genetic condition in future pregnancies.Although prenatal ES is an exciting new way to improve diagnosis rates for structural differences, it has some challenges. While the test is very detailed, it may not always find a genetic explanation and sometimes the results are difficult to interpret. For example, genetic changes can be found where their significance for the pregnancy is unclear.More recently, two studies have now shown that prenatal ES can find a genetic diagnosis in at least 10% of pregnancies with structural differences where standard chromosome testing has been negative. This paper reviews these studies, along with earlier evidence on ES and provides clinicians with guidance for future practice.