bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Crystal Structure of Bromide-BoundGtACR1 Reveals a Pre-Activated State in the Transmembrane Anion Tunnel
Authors: Li Hai , Huang Chia-Ying , Govorunova Elena G. , Sineshchekov Oleg A. , Wang Meitian , Zheng Lei , Spudich John L. 
Published: January 2021

AbstractThe crystal structure of the light-gated anion channelGtACR1 reported in our previous research article (Li et al., 2019) revealed a continuous tunnel traversing the protein from extracellular to intracellular pores. We proposed the tunnel as the conductance channel closed by three constrictions: C1 in the extracellular half, mid-membrane C2 containing the photoactive site, and C3 on the cytoplasmic side. Reported here, the crystal structure of bromide-boundGtACR1 reveals structural changes that relax the C1 and C3 constrictions, including a novel salt-bridge switch mechanism involving C1 and the photoactive site. These findings indicate that substrate binding induces a transition from an inactivated state to a pre-activated state in the dark that facilitates channel opening by reducing free energy in the tunnel constrictions. The results provide direct evidence that the tunnel is the closed form of the channel ofGtACR1 and shed light on the light-gated channel activation mechanism.Impact StatementSubstrate-induced structural changes inGtACR1 provide new insight into the chemical mechanism of natural light-gated anion conductance, and facilitate its optimization for photoinhibition of neuron firing in optogenetics.
Flagellin triggers mesophyll dehydration: An early PTI defense against bacterial establishment in intercellular spaces
Authors: Dalal Ahan , Attia Ziv , Moshelion Menachem 
Published: January 2021

ABSTRACTPlants have evolved various mechanisms to defend themselves against pathogens. Many pathogens induce the formation of water-soaked lesions during early infection under conditions of high atmospheric humidity. These water-soaked spots are caused by the disruption of the plasma membrane or cell wall integrity due to various activities of effector proteins during infection. We hypothesized that bacterial PAMP-flagellin plays a role in modulating the cell-membrane permeability that controls the availability of water in the apoplast, to prevent bacterial establishment on the cell wall during the early stages of the PAMP-triggered immunity (PTI) response. Our results revealed that the conductivity of hydraulic pathways in the leaf was reduced in response to flagellin22 (flg22). The cellular osmotic water permeability (Pf) of both mesophyll cells and bundlesheath cells was dramatically reduced in response to flg22 treatment. Moreover, the whole-leaf hydraulic conductance (Kleaf) was also reduced in response to flg22 treatment. The fact that the Pfof mesophyll cells of an aquaporin (AQP) mutant was not affected by the flg22 treatment suggests the involvement of AQP channels in the flg22-induced Pfreduction signal transduction pathway. We conclude that the binding of flagellin to their receptors elicits signals to close AQPs, consequently reducing the water content of the cell wall and intercellular spaces and leading to a more negative water potential. This serves as an early PTI response to pathogen attack, which, in turn, might decrease the rate of bacterial growth and establishment in the apoplast.Significance statementWe report that the membrane osmotic water permeability of both leaf mesophyll and vascular bundle-sheath cells is reduced in response to treatment with flagellin22. We suggest that this mechanism for cell dehydration may serve as an apoplastic defense response, to limit the chances of bacterial pathogens becoming established on the walls of leaf mesophyll cells.
Intermittent Bulk Release of Human Cytomegalovirus
Authors: Flomm Felix J. , Soh Timothy K. , Schneider Carola , Wedemann Linda , Britt Hannah M. , Thalassinos Konstantinos , Pfitzner Søren , Reimer Rudolph , Grünewald Kay , Bosse Jens B. 
Published: January 2021

AbstractHuman Cytomegalovirus (HCMV) can infect a variety of cell types by using virions of varying glycoprotein compositions. It is still unclear how this diversity is generated, but spatio-temporally separated envelopment and egress pathways might play a role. So far, one egress pathway has been described in which HCMV particles are individually enveloped into small vesicles and are subsequently exocytosed continuously. However, some studies have also found enveloped virus particles inside multivesicular structures but could not link them to productive egress or degradation pathways.We used a novel 3D-CLEM workflow allowing us to investigate these structures in HCMV morphogenesis and egress at high spatio-temporal resolution. We found that multiple envelopment events occurred at individual vesicles leading to multiviral bodies (MViBs), which subsequently traversed the cytoplasm to release virions as intermittent bulk pulses at the plasma membrane to form extracellular virus accumulations (EVAs). Our data support the existence of a novelbona fideHCMV egress pathway, which opens the gate to evaluate divergent egress pathways in generating virion diversity.
A genome wide copper-sensitized screen identifies novel regulators of mitochondrial cytochrome c oxidase activity
Authors: Garza Natalie M. , Griffin Aaron T. , Zulkifli Mohammad , Qiu Chenxi , Kaplan Craig D. , Gohil Vishal M. 
Published: January 2021

ABSTRACTCopper is essential for the activity and stability of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Loss-of-function mutations in genes required for copper transport to CcO result in fatal human disorders. Despite the fundamental importance of copper in mitochondrial and organismal physiology, systematic characterization of genes that regulate mitochondrial copper homeostasis is lacking. To identify genes required for mitochondrial copper homeostasis, we performed a genome-wide copper-sensitized screen using DNA barcoded yeast deletion library. Our screen recovered a number of genes known to be involved in cellular copper homeostasis while revealing genes previously not linked to mitochondrial copper biology. These newly identified genes include the subunits of the adaptor protein 3 complex (AP-3) and components of the cellular pH-sensing pathway-Rim20 and Rim21, both of which are known to affect vacuolar function. We find that AP-3 and the Rim mutants impact mitochondrial CcO function by maintaining vacuolar acidity. CcO activity of these mutants could be rescued by either restoring vacuolar pH or by supplementing growth media with additional copper. Consistent with these genetic data, pharmacological inhibition of the vacuolar proton pump leads to decreased mitochondrial copper content and a concomitant decrease in CcO abundance and activity. Taken together, our study uncovered a number of novel genetic regulators of mitochondrial copper homeostasis and provided a mechanism by which vacuolar pH impacts mitochondrial respiration through copper homeostasis.
Benchmarking Oxford Nanopore read assemblers for high-quality molluscan genomes
Authors: Sun Jin , Li Runsheng , Chen Chong , Sigwart Julia D. , Kocot Kevin M. 
Published: January 2021

SummaryChoosing the optimum assembly approach is essential to achieving a high-quality genome assembly suitable for comparative and evolutionary genomic investigations. Significant recent progress in long-read sequencing technologies such as PacBio and Oxford Nanopore Technologies (ONT) also brought about a large variety of assemblers. Although these have been extensively tested on model species such asHomo sapiensandDrosophila melanogaster, such benchmarking has not been done in Mollusca which lacks widely adopted model species. Molluscan genomes are notoriously rich in repeats and are often highly heterozygous, making their assembly challenging. Here, we benchmarked 10 assemblers based on ONT raw reads from two published molluscan genomes of differing properties, the gastropodChrysomallon squamiferum(356.6Mb, 1.59% heterozygosity) and the bivalveMytilus coruscus(1593Mb, 1.94% heterozygosity). By optimising the assembly pipeline, we greatly improved both genomes from previously published versions. Our results suggested that 40-50X of ONT reads are sufficient for high-quality genomes, with Flye being the recommended assembler for compact and less heterozygous genomes exemplified byC. squamiferum, while NextDenovo excelled for more repetitive and heterozygous molluscan genomes exemplified byM. coruscus. A phylogenomic analysis utilising the two updated genomes with other 32 published high-quality lophotrochozoan genomes resulted in maximum support across all nodes, and we show that improved genome quality also leads to more complete matrices for phylogenomic inferences. Our benchmarking will ensure the efficiency in future assemblies for molluscs and perhaps also other marine phyla with few genomes available.
Rejuveinix Reverses Severe Inflammatory Lung Damage in a Mouse Model of Fatal Sepsis
Authors: Uckun Fatih M. , Ozercan Ibrahim H. , Orhan Cemal , Gitterle Marcus , Sahin Kazim 
Published: January 2021

AbstractWe set out to determine if our anti-sepsis drug candidate Rejuveinix (RJX) can effectively treat systemic inflammation in a mouse model of sepsis when used at a dose level that is >10-times lower than its maximum tolerated dose (MTD) for human subjects. Our findings obtained in the LPS-GalN mouse model of fatal sepsis provide experimental evidence that RJX exhibits potent single-agent anti-inflammatory activity and reverses very severe inflammatory lung injury when used therapeutically, thereby significantly improving the survival outcome. These findings demonstrate the clinical impact potential of RJX for the treatment of severe sepsis.
Rapid inactivation of SARS-CoV-2 on copper touch surfaces determined using a cell culture infectivity assay
Authors: Bryant Catherine , Wilks Sandra A. , Keevil C. William 
Published: January 2021

ABSTRACTCOVID-19, caused by SARS-CoV-2, was first reported in China in 2019 and has transmitted rapidly around the world, currently responsible for 83 million reported cases and over 1.8 million deaths. The mode of transmission is believed principally to be airborne exposure to respiratory droplets from symptomatic and asymptomatic patients but there is also a risk of the droplets contaminating fomites such as touch surfaces including door handles, stair rails etc, leading to hand pick up and transfer to eyes, nose and mouth. We have previously shown that human coronavirus 229E survives for more than 5 days on inanimate surfaces and another laboratory reproduced this for SARS-CoV-2 this year. However, we showed rapid inactivation of Hu-CoV-229E within 10 minutes on different copper surfaces while the other laboratory indicated this took 4 hours for SARS-CoV-2. So why the difference? We have repeated our work with SARS-CoV-2 and can confirm that this coronavirus can be inactivated on copper surfaces in as little as 1 minute. We discuss why the 4 hour result may be technically flawed.
Unveiling everyday discrimination. Two field experiments on discrimination against religious minorities in day‐to‐day interactions
Authors: Aidenberger Amelie , Doehne Malte 
Published: January 2021

AbstractIn recent years—particularly since the beginning of the refugee crisis in 2015—the political debate about issues of Islamophobia and resentment of Muslims has gained new momentum. Our research contributes to the growing experimental literature focusing on these phenomena. Unlike most previous empirical investigations, the present study does not examine “large scale” discrimination against Muslim minorities in situations which occur only periodically throughout an individual's life (e.g., on the rental‐, labor‐, or partner market); rather, it sheds light on (minor) discrimination events that occur on a day‐to‐day basis. Such “everyday discrimination” has been shown to be particularly detrimental to physical and psychological health. Specifically, our research examines the effect of open displays of religious identification—wearing a Muslim headscarf—on everyday discrimination against female Muslims. We report the results of two natural field experiments in Switzerland designed to examine such forms of day‐to‐day discrimination. Study 1 focuses on differential sanctioning, whereas study 2 investigates differences regarding helping behavior. We found pronounced discrimination against women wearing a headscarf in two distinctly different types of everyday interactions. In both scenarios, headscarf‐wearing confederates were treated less favorably than bare‐headed ones: they were sanctioned more often for violating the “stand right, walk left”‐norm on escalators and received less help when asking for a favor (borrowing a mobile phone for an urgent call).
Staying at home or going out? Leadership response to the COVID‐19 crisis in Greece and Sweden
Authors: Petridou Evangelia , Zahariadis Nikolaos 
Published: January 2021

AbstractIn this article, we investigate the leadership response to the COVID‐19 pandemic crisis in Greece and Sweden based on the strategic leadership framework put forth by Boin, 't Hart, Stern and Sundelius. We seek to understand the contextual (institutional, administrative and political) factors explaining the differences in stringency of measures and centralization of response in Greece and Sweden, respectively. What trade‐offs did public leaders implement between effectiveness and efficiency to successfully manage the crisis? We find that reliance on expertise plays out differently in centralized and decentralized structure, while a salient lesson drawn for practitioners is that there is more than one path to successful crisis leadership response contingent on institutional capacity, bureaucratic autonomy and political system. The article concludes with implications for leadership response during crises and practical lessons for crisis managers.
Low‐grade albuminuria is associated with high cardiovascular risk in CVD‐free and normoalbuminuric Chinese adults: Results from the REACTION study
Authors: Li Bing , Chen Kang , Wang Jie , Wang Yuxia , Li Binqi , Li Ran , Gao Zhengnan , Tang Xulei , Yan Li , Wan Qin , Wang Weiqing , Qin Guijun , Chen Lulu , Mu Yiming 
Published: January 2021

AbstractBackgroundData are limited with regard to the association between low‐grade albuminuria (below the threshold of microalbuminuria) and high cardiovascular risk in normoalbuminuric Chinese adults free of cardiovascular disease (CVD).MethodsA total of 32 650 participants aged over 40 years from seven regional centers in China were included in this study. The single‐void first morning urine sample was collected to measure the urinary albumin to creatinine ratio (UACR) and the data were divided into sex‐specific quartiles. The Framingham Risk Score (FRS) was used to identify participants at high risk of developing coronary heart disease (CHD) over the next 10 years and the association between low‐grade albuminuria and high 10‐year Framingham risk for CHD (FRS ≥20%) was investigated.ResultsAmong males and females, the prevalence of cardiometabolic risk factors (diabetes, hypertension, and dyslipidemia) increased markedly with the elevation of UACR quartiles. Logistic regression analysis showed that the odds ratios (ORs) for high 10‐year risk of CHD increased significantly from the second quartile in males (UACR: 4.78 ~ 7.53 mg/g, OR = 1.21, 95% confidence interval [CI]: 1.05‐1.40) and the third quartile in females (UACR: 9.13 ~ 15.04 mg/g, OR = 3.07, 95% CI: 1.75‐5.40). Stratified analysis showed that in males, the association was especially pronounced in elderly, overweight/obese participants and those without diabetes and hypertension whereas in females, the association was especially pronounced in elderly, overweight/obese participants and those without diabetes and with hypertension.ConclusionsLow‐grade albuminuria was significantly associated with high 10‐year cardiovascular risk among CVD‐free and normoalbuminuric Chinese adults.
Interpretation of Pumping Tests in Heterogeneous Aquifers with Constant Head Boundary
Authors: Pechstein Armin , Copty Nadim K. 
Published: January 2021

AbstractThis paper investigates the impact of heterogeneity of the transmissivity field on the interpretation of steady‐state pumping test data from aquifer systems delimited by constant head boundaries such as aquifers adjacent to lakes or rivers. Spatially variable transmissivity fields are randomly generated and used to simulate the drawdown due to a pumping well located at different distances from a constant head boundary. The steady‐state drawdown simulated at different observation wells are then interpreted using the Hantush method (Hantush 1959). The numerical simulations show that, in contrast to the case of infinite aquifer domains, the interpreted transmissivity varies depending on well locations and the separation distance between pumping well and boundary relative to the correlation length. The ensemble‐averaged estimated transmissivity varies between the geometric mean and the arithmetic mean, and can even exceed the arithmetic mean in a narrow domain adjacent to the boundary. It approaches the geometric mean of the underlying transmissivity field only if the distance between the pumping well is more than 20 times the characteristic length of the transmissivity field.
Clinical cell‐based versus cell‐free regenerative endodontics: clarification of concept and term
Authors: Lin L. M. , Huang G. T‐J. , Sigurdsson A. , Kahler B. 
Published: January 2021

AbstractThere is no consensus on the true meaning of clinical regenerative endodontics, and there is confusion over the concept and the term. Commonly used terms include revitalization and revascularization. The clinical methods for endodontic revitalization procedures and the tissue engineering concept differ depending on whether there is exogenous delivery of cells – called cell therapy, or not. Here, in this review, the difference is clarified by emphasizing the correct terminology: cell‐free versus cell‐based regenerative endodontic therapy (CF‐RET versus CB‐RET). The revitalization procedures practised clinically do not fit into the modern tissue engineering concepts of pulp regeneration but can be categorized as CF‐RET. The modern tissue engineering concept in pulp regeneration is a CB‐RET, which so far is at the clinical trial stage. However, histological examination of teeth following regenerative endodontic treatments reveals healing with repair derived from stem cells that originate from the periodontal, bone and other tissues. The aim of regenerative endodontics is regeneration of the pulp–dentine complex. This review discusses why CF‐RET is unlikely to regenerate a pulp–dentine complex with current protocols. The American Association of Endodontists and the European Society of Endodontology have not yet recommended autologous stem cell transplantation (CB‐RERT) which aspires for regeneration. Therefore, an understanding of the concept, term, difficulties and differences in current protocols is important for the clinician. However, rather than being discouraged that ideal regeneration has not been achieved to date, repair can be an acceptable outcome in clinical regenerative endodontics as it has also been accepted in medicine. Repair should also be considered in the context that resolution of the clinical signs/symptoms of pulp necrosis/apical periodontitis is generally reliably obtained in clinical regenerative endodontics.
Val‐Val‐Tyr‐Pro protects against non‐alcoholic steatohepatitis in mice by modulating the gut microbiota and gut‐liver axis activation
Authors: Xie Xinshu , Zhang Lang , Yuan Shun , Li Huilan , Zheng Chaojun , Xie Saisai , Sun Yongbing , Zhang Changhua , Wang Rikang , Jin Yi 
Published: January 2021

AbstractVal‐Val‐Tyr‐Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride‐induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non‐alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L‐02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine‐choline‐deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non‐esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis‐related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae, coriobacteriacease, Desulfovibrionaceae, S24‐7 and Bacteroidia in high‐fat diet (HFD)‐fed mice, however, VVYP reduced the abundance of Lactobacillus. Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)‐associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut‐liver axis activation. VVYP might be a promising drug candidate for NASH.
Older patients’ perspectives and experience of hospitalisation during the COVID‐19 pandemic: a qualitative explorative study
Authors: Nielsen Dorthe Susanne , Hansen Rikke Frøslev , Beck Sanne Have , Wensien Jette , Masud Tahir , Ryg Jesper 
Published: January 2021

AbstractBackground and ObjectivesThe aim of this study was to gain in‐depth knowledge and an increased understanding on how isolation from close relatives and carers, during the COVID‐19 pandemic, impacted older patients during hospitalisation in a Geriatric department.MethodWe conducted a qualitative study using semi‐structured interviews and a phenomenological‐hermeneutic approach, to get an understanding of the older participants' perspectives and lived experiences. Complete interviews were available for 11 patients—six men and five women, between 69 and 91 years of age.ResultsThe participants' narratives identified several themes. Feeling isolated from and having no contact with close relatives or carers was prominent. The COVID‐19 pandemic created fear and anxiety among hospitalized patients. Relationships with family members and some staff became strained. The transformation from being “a person” to being “a patient” and loss of dignity, autonomy and a “sense of self” were themes identified in the analysis. Although virtual contact can't replace the real world, the use of technology to maintain contact with family and carers, and the need for help from hospital staff in facilitating this contact was deemed important. The environment of care was a prominent theme. The attitude of staff made a difference to how patients felt and some patients expressed a loss of decision‐making capability. The interviews were challenging in some cases because the interviews had to be interrupted or shortened due to ethical considerations around the individual person's needs and condition.Conclusions and implication for practiceOur study provided in‐depth knowledge on how older patients experienced hospitalisation during the COVID‐19 pandemic in a Danish hospital. The results emphasise that compassionate care includes a willingness to listen to older patients' narratives and to imagine life as depicted by them. This can lead to better understanding of an individual person's needs and increase the quality of care provided.