bluuebunny/crossref_metadata_2025_split huggingface dataset:
The P5-ATPase ATP13A1 modulates MR1-mediated antigen presentation
Authors: Kulicke Corinna A. , Zan Erica De , Hein Zeynep , Gonzalez-Lopez Claudia , Ghanwat Swapnil , Veerapen Natacha , Besra Gurdyal S. , Klenerman Paul , Christianson John C. , Springer Sebastian , Nijman Sebastian , Cerundolo Vincenzo , Salio Mariolina 
Published: May 2021

AbstractThe monomorphic antigen presenting molecule MHC-I-related protein 1 (MR1) presents small molecule metabolites to mucosal-associated invariant T (MAIT) cells. The MR1-MAIT cell axis has been implicated in a variety of infectious and non-communicable diseases and recent studies have begun to develop an understanding of the molecular mechanisms underlying this specialised antigen presentation pathway. Yet, the proteins regulating MR1 folding, loading, stability, and surface expression remain to be identified. Here, we performed a gene trap screen to discover novel modulators of MR1 surface expression through insertional mutagenesis of an MR1-overexpressing clone derived from the near-haploid human cell line HAP1 (HAP1.MR1). The most significant positive regulators identified included β2-microglobulin, a known regulator of MR1 surface expression, and ATP13A1, a P5-ATPase in the endoplasmic reticulum (ER) with putative transporter function not previously associated with MR1-mediated antigen presentation. CRISPR/Cas9-mediated knock-out of ATP13A1 in both HAP1.MR1 and THP-1 cell lines revealed a profound reduction in MR1 protein levels and a concomitant functional defect specific to MR1-mediated antigen presentation. Collectively, these data are consistent with the ER-resident ATP13A1 as a key post-transcriptional determinant of MR1 surface expression.
APOE4 expression confers a mild, persistent reduction in neurovascular function in the visual cortex and hippocampus of awake mice
Authors: Bonnar Orla , Shaw Kira , Grijseels Dori M. , Clarke Devin , Bell Laura , Anderle Silvia , King Sarah L. , Hall Catherine N. 
Published: May 2021

AbstractYoung mice possessing the e4 allele of the Apolipoprotein (APOE) gene (a risk factor for Alzheimer’s disease (AD)) have previously been shown to have dramatic decreases in vascular function, suggesting APOE4 may confer its risk via the vasculature. However, in human carriers, vascular and cognitive function decrease later in life. Mouse data may be confounded by an increased impact of anaesthesia and surgery in APOE4 animals, and has also focused on sensory cortices, ignoring medial lobe structures more sensitive to AD.To clarify how APOE4 expression alters neurovascular function, we studied the visual cortex and hippocampus of awake APOE3 and APOE4 targeted replacement mice, using 2-photon microscopy of neurons and blood vessels.We found milder vascular deficits than studies using anaesthetised preparations: functional hyperaemia was unaffected in APOE4 mice and neuronal or vascular function did not decrease with age. Instead, vascular responsiveness was lower at all ages, arteriole vasomotion was reduced and neuronal calcium signals during visual stimulation were increased. This suggests that, independently, APOE4 expression is not catastrophic but alters neurovascular physiology towards a state more sensitive to insults such as surgery or beta amyloid accumulation. Understanding how APOE4 expression interacts with these insults will be critical for understanding the emergence of AD in APOE4 carriers.
How many replicates to accurately estimate fish biodiversity using environmental DNA on coral reefs?
Authors: Stauffer Salomé , Jucker Meret , Keggin Thomas , Marques Virginie , Andrello Marco , Bessudo Sandra , Cheutin Marie-Charlotte , Borrero-Pérez Giomar Helena , Richards Eilísh , Dejean Tony , Hocdé Régis , Juhel Jean-Baptiste , Ladino Felipe , Letessier Tom B. , Loiseau Nicolas , Maire Eva , Mouillot David , Martinezguerra Maria Mutis , Manel Stéphanie , Fernández Andrea Polanco , Valentini Alice , Velez Laure , Albouy Camille , Pellissier Loïc , Waldock Conor 
Published: May 2021

AbstractQuantifying the diversity of species in rich tropical marine environments remains challenging. Environmental DNA (eDNA) metabarcoding is a promising tool to face this challenge through the filtering, amplification, and sequencing of DNA traces from water samples. However, the reliability of biodiversity detection from eDNA samples can be low in marine environments because eDNA density is low and certainly patchy in this vast, heterogenous and dynamic environment. So, the number of sampling replicates and filtered volume necessary to obtain accurate estimates of biodiversity in rich tropical marine environments using eDNA metabarcoding is still unknown. Here, we used a paired sampling design of 30L per replicate on 68 reef transects from 8 sites in three tropical regions and identified fish Molecular Taxonomic Units (MOTUs) using a 12S marker. We quantified local biodiversity variation as MOTU richness, compositional turnover and compositional nestedness between replicated pairs of seawater samples. We report strong turnover of MOTUs between replicated pairs of samples undertaken in the same location, time, and conditions. Paired samples contained non-overlapping assemblages rather than subsets of one-another. As a result, localised diversity accumulation curves showed that even 6 replicates (180L) in the same location underestimated local diversity (for an area <1km). However, sampling of regional diversity using ∼25 replicates in variable locations (often covering 10s of km) achieved saturation of biodiversity accumulation curves. Our results demonstrate high variability of diversity estimates perhaps arising from heterogeneous and local distribution of eDNA distribution in seawater or highly skewed frequencies of eDNA traces. This high compositional variability has consequences for using eDNA to monitor temporal and spatial biodiversity changes of local assemblages. Future biomonitoring efforts could be strongly undermined by a high level of false-negative detections under low replication protocols. We reveal the need to increase replicates or increase sampled water volume to better inform management of marine biodiversity using eDNA.
Decomposing age effects in EEG alpha power
Authors: Tröndle Marius , Popov Tzvetan , Pedroni Andreas , Pfeiffer Christian , Barańczuk-Turska Zofia , Langer Nicolas 
Published: May 2021

AbstractIncreasing life expectancy is prompting the need to understand how the brain changes during healthy aging. Research utilizing Electroencephalography (EEG) has found that the power of alpha oscillations decrease from adulthood on. However, non-oscillatory (aperiodic) components in the data may confound results and thus require re-investigation of these findings. The present report aims at analyzing a pilot and two additional independent samples (total N = 533) of resting-state EEG from healthy young and elderly individuals. A newly developed algorithm will be utilized that allows the decomposition of the measured signal into aperiodic and aperiodic-adjusted signal components. By using multivariate sequential Bayesian updating of the age effect in each signal component, evidence across the datasets will be accumulated. It is hypothesized that previously reported age-related alpha power differences will disappear when absolute power is adjusted for the aperiodic signal component. Consequently, age-related differences in the intercept and slope of the aperiodic signal component are expected. Importantly, using a battery of neuropsychological tests, we will assess how the previously reported relationship between cognitive functions and alpha oscillations changes when taking the aperiodic signal into account; this will be done on data of the young and aged individuals separately. The aperiodic signal components and adjusted alpha parameters could potentially offer a promising biomarker for cognitive decline, thus finally the test–retest reliability of the aperiodic and aperiodic-adjusted signal components will be assessed.
A robust method for performing 1H-NMR lipidomics in embryonic zebrafish
Authors: Morgan Rhiannon S. , Walmsley Gemma , Peffers Mandy J. , Barrett-Jolley Richard , Phelan Marie M. 
Published: May 2021

AbstractThe embryonic zebrafish is an ideal system for lipid analyses with relevance to many areas of bioscience research, including biomarkers and therapeutics. Research in this area has been hampered by difficulties in extracting, identifying and quantifying lipids. We employed 1H-NMR at 700MHz to profile lipids in developing zebrafish embryos. The optimal method for lipidomics in embryonic zebrafish incorporated rapid lipid extraction using chloroform and an environment without oxygen depletion. Pools of 10 embryos gave the most acceptable signal-to-noise ratio, and the inclusion of chorions in the sample had no significant effect on lipid abundances. Embryos, bisected into cranial (head and yolk sac) and caudal (tail) regions, were compared by principal component analysis and analysis of variance. The lipid spectra (including lipid annotation) are available in the public repository MetaboLights (MTBLS2396).
Structural basis for the inhibition of the Bacillus subtilis c-di-AMP cyclase CdaA by the phosphoglucomutase GlmM
Authors: Pathania Monisha , Tosi Tommaso , Millership Charlotte , Hoshiga Fumiya , Morgan Rhodri M. L. , Freemont Paul S. , Gründling Angelika 
Published: May 2021

AbstractCyclic-di-adenosine monophosphate (c-di-AMP) is an important nucleotide signalling molecule, which plays a key role in osmotic regulation in bacteria. Cellular c-di-AMP levels are tightly regulated, as both high and low levels have a negative impact on bacterial growth. Here, we investigated how the activity of the main Bacillus subtilis c-di-AMP cyclase CdaA is regulated by the phosphoglucomutase GlmM. c-di-AMP is produced from two molecules of ATP by proteins containing a deadenylate cyclase (DAC) domain. CdaA is a membrane-linked cyclase with an N-terminal transmembrane domain followed by the cytoplasmic DAC domain. Here we show, using the soluble catalytic B. subtilis CdaACD domain and purified full-length GlmM or the GlmMF369 variant lacking the C-terminal flexible domain 4, that the cyclase and phosphoglucomutase form a stable complex in vitro and that GlmM is a potent cyclase inhibitor. We determined the crystal structure of the individual B. subtilis CdaACD and GlmM proteins, both of which form dimers in the structures, and of the CdaACD:GlmMF369 complex. In the complex structure, a CdaACD dimer is bound to a GlmMF369 dimer in such a manner that GlmM blocks the oligomerization of CdaACD and formation of active head-to-head cyclase oligomers, thus providing molecular details on how GlmM acts as cyclase inhibitor. The function of a key amino acid residue in CdaACD in complex formation was confirmed by mutagenesis analysis. As the amino acids at the CdaACD:GlmM interphase are conserved, we propose that the observed inhibition mechanism of CdaA by GlmM is conserved among Firmicutes.
TatA and TatB generate a hydrophobic mismatch that is important for function and assembly of the Tat translocon in Escherichia coli
Authors: Mehner-Breitfeld Denise , Ringel Michael T. , Tichy Daniel Alexander , Endter Laura J. , Stroh Kai Steffen , Lünsdorf Heinrich , Risselada Herre Jelger , Brüser Thomas 
Published: May 2021

AbstractThe Tat system has the unique purpose to translocate folded proteins across energy-transducing membranes. It occurs in bacteria and archaea, as well as in eukaryotic organelles of bacterial origin. In the bacterial model system Escherichia coli, the three components TatA, TatB, and TatC assemble to functional translocons. TatA and TatB both possess an N-terminal transmembrane helix (TMH) that is followed by an amphipathic helix (APH). The TMHs of TatA and TatB generate a hydrophobic mismatch with only 12 consecutive hydrophobic residues that span the membrane. We shortened or extended this stretch of hydrophobic residues in either TatA, TatB, or both, and analyzed effects on transport functionality and translocon assembly. The wild type length functioned best but was not an absolute requirement, as some variation was clearly tolerated. Defects of shortenings or extensions were enhanced by simultaneous mutations in TatA and TatB, indicating partial compensations of mutations in TatA by wild type TatB or vice versa. Length variation in TatB destabilized TatBC-containing complexes, revealing that the 12-residues-length is important for Tat component interactions and translocon assembly. To also address potential effects on TatA associations, we characterized these by metal tagging transmission electron microscopy and carried out molecular dynamics simulations. In these simulations, interacting short TMHs of larger TatA assemblies were thinning the membrane together with laterally aligned tilted APHs that generated a deep V-shaped groove. The conserved length of 12 hydrophobic residues may thus not only be important for translocon interactions, but also for a membrane destabilization during Tat transport. If this is the case, the specific short length could be a compromise between functionality and proton leakage minimization.
Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes
Authors: Monti Remo , Rautenstrauch Pia , Ghanbari Mahsa , James Alva Rani , Ohler Uwe , Konigorski Stefan , Lippert Christoph 
Published: May 2021

AbstractHere we present an exome-wide rare genetic variant association study for 30 blood biomarkers in 191,971 individuals in the UK Biobank. We compare gene-based association tests for separate functional variant categories to increase interpretability and identify 193 significant gene-biomarker associations. Genes associated with biomarkers were ~ 4.5-fold enriched for conferring Mendelian disorders. In addition to performing weighted gene-based variant collapsing tests, we design and apply variant-category-specific kernel-based tests that integrate quantitative functional variant effect predictions for missense variants, splicing and the binding of RNA-binding proteins. For these tests, we present a statistically powerful and computationally efficient combination of the likelihood-ratio and score tests that found 36% more associations than the score test alone. Kernel-based tests identified 13% more associations than their gene-based collapsing counterparts and had advantages in the presence of gain of function missense variants. We introduce local collapsing by amino acid position for missense variants and use it to interpret associations and identify potential novel gain of function variants inPIEZO1. Our results show the benefits of investigating different functional mechanisms when performing rare-variant association tests, and demonstrate pervasive rare-variant contribution to biomarker variability.
The evolution of the phenylpropanoid pathway entailed pronounced radiations and divergences of enzyme families
Authors: de Vries Sophie , Fürst-Jansen Janine MR , Irisarri Iker , Ashok Amra Dhabalia , Ischebeck Till , Feussner Kirstin , Abreu Ilka N , Petersen Maike , Feussner Ivo , de Vries Jan 
Published: May 2021

ABSTRACTLand plants constantly respond to fluctuations in their environment. Part of their response is the production of a diverse repertoire of specialized metabolites. One of the foremost sources for metabolites relevant to environmental responses is the phenylpropanoid pathway, which was long thought to be a land plant-specific adaptation shaped by selective forces in the terrestrial habitat. Recent data have however revealed that streptophyte algae, the algal relatives of land plants, have candidates for the genetic toolkit for phenylpropanoid biosynthesis and produce phenylpropanoid-derived metabolites. Using phylogenetic and sequence analyses, we here show that the enzyme families that orchestrate pivotal steps in phenylpropanoid biosynthesis have independently undergone pronounced radiations and divergence in multiple lineages of major groups of land plants; sister to many of these radiated gene families are streptophyte algal candidates for these enzymes. These radiations suggest a high evolutionary versatility in the enzyme families involved in the phenylpropanoid-derived metabolism across embryophytes. We suggest that this versatility likely translates into functional divergence and may explain the key to one of the defining traits of embryophytes: a rich specialized metabolism.
Controlling shareholders' stock pledges and strategic change: the moderating effects of corporate governance
Authors: Zhong Xi , Wan He , Peng Qiuping 
Published: May 2021

PurposeThe authors analyze the effects of controlling shareholders' stock pledging on firms' strategic change behavior, and investigate how the balance of power between shareholders and analyst coverage moderates those effects.Design/methodology/approachEmploying fixed effects models, the authors test hypotheses based on Chinese listed company data from 2011 to 2017.FindingsControlling shareholders' stock pledges has a negative effect on strategic change. As the balance of power among shareholders and/or analyst coverage increases, it mitigates the effect of controlling shareholder stock pledges on strategic change. In particular, the balance of power between shareholders and analyst coverage weakened the relationship between controlling shareholder stock pledges and strategic change. Lastly, after distinguishing family from nonfamily firms, the authors discovered that these findings only held for family firms.Originality/valueThis study makes important contributions to strategic change, stock pledge and family firm literature, and also provides guidance on firms' strategic change practices.
Outsourcing of healthcare services in a smart city of Eastern India
Authors: Barik Susanta Kumar , Rout Himanshu Sekhar 
Published: May 2021

PurposeOwing to the rising costs and shrinking budgets; inefficiency can be observed in the financing and delivery of health service both in the private and public sectors, which is not only causing organizations to reconsider their management patterns but also to use new strategies to achieve competitive merits in the current world of business. Outsourcing is one of the best alternates. The purpose of this paper is to study: the nature and magnitude of outsourcing of health-care services in a Smart City of Eastern India; the motives behind outsourcing: and the factors affecting outsourcing decisions.Design/methodology/approachThe study was conducted in Bhubaneswar, a Smart City of Eastern India and capital of Odisha State. Data relating to the outsourcing of health-care services were collected from 40 hospitals (each having a minimum of 10 beds) through a structured schedule. Descriptive statistics were calculated through Statistical Package for Social Science to substantiate the objectives.FindingsMost of the clinical services were outsourced by small hospitals, while a significant portion of non-clinical services were outsourced by large and medium hospitals. Reduction in cost and better management control were the major driving forces of outsourcing. Loss of control over service providers and quality of measurement were considered as the main disadvantages in the decision-making process of not outsourcing the services by hospitals.Originality/valueThe study is the first-ever survey based on empirical evidence about the state of facilities management services outsourced in public and private hospitals in Odisha, India. The paper concluded that the effect of outsourcing did not synchronize successfully as shown in international literature.
Building a resilient public health system for international migrant workers: a case study and policy brief for COVID-19 and beyond
Authors: Rojanaworarit Chanapong , El Bouzaidi Sarah 
Published: May 2021

PurposeThis article analyzes deficiencies in public health services for international migrant workers (IMWs) during the COVID-19 pandemic and provides a policy brief for improvement of the public health system.Design/methodology/approachA COVID-19 outbreak that initially clustered in IMWs and further contributed to the resurgence of the disease across Thailand in December 2020 was analyzed to address the deficiencies in public health services based on the framework of the 10 Essential Public Health Services (EPHS). The EPHS framework was also applied to develop policy options and recommendations in the subsequent policy brief.FindingsThis outbreak unveiled unique challenges that make IMWs more vulnerable to COVID-19. The public health system, challenged by the COVID-19 outbreak among IMWs, manifested deficiencies in the planning and implementation of all essential services. Delayed detection of the outbreak along with the lack of policy accommodating undocumented IMWs and the lack of equitable access to testing and treatment for COVID-19 resulted in the transmission of the disease that harmed the public at large.Originality/valueThe comprehensive analysis of the deficiencies in public health services for IMWs enabled a clear description of problems that could be further prioritized by relevant stakeholders. The policy brief provides policymakers with evidence-based recommendations for improving public health services for IMWs during the COVID-19 pandemic and beyond.
Improving vegetable supply chain collaboration: a case study in Vietnam
Authors: Yang Ying , Pham Mai Ha , Yang Biao , Sun Jun Wei , Tran Phuong Nguyen Thu 
Published: May 2021

Purpose
While various aspects of the vegetable supply chain (SC) have been increasingly studied, most studies tend to investigate the downstream part of the SC in terms of customer demand and product quality. Relatively fewer studies have focused on upstream suppliers/farmers. This study aims to understand upstream farmers’ positions in different types of vegetable SCs and identify ways of enhancing sustainable vegetable SC collaboration.

Design/methodology/approach
This study is based on an in-depth case study of a cooperative SC in Vietnam from the perspectives of both the cooperative and its farmers.

Findings
The study found that cooperative SCs are the most appropriate for Vietnamese farmers. It also identified the key activities needed to engage farmers with cooperative SCs and the mechanisms that the cooperative needs to develop. Cooperative SCs can be enhanced only when farmers are motivated to engage in SC activities and when the cooperative implements a robust management mechanism.

Originality/value
This study provides new, insightful results on how to engage with small fragmented farmers for SC collaboration and how to enhance the roles of cooperative SCs in the vegetable industry in Vietnam. It also provides information for policymakers to support sustainable vegetable SC development and maintain its sustainability.
The emerging importance of “homestays” in the Indian hospitality sector
Authors: Kulshreshtha Sandeep , Kulshrestha Ruchika 
Published: May 2021

Purpose
The purpose of this paper is to analyse the potential of “homestays” and also observe the trends related to this emerging concept in India. This paper also discusses various challenges faced by the owners of homestays.

Design/methodology/approach
This paper is based on an exploratory study that sought to collect factual data about the present scenario and the emerging trends related to homestays. A qualitative case study method was used to analyse the actual practices followed by stakeholders. This paper expresses the viewpoint of the authors on the augmented demand for homestay supported by secondary data published in several academic papers and reports published by various government departments. The author interviewed a number of homestay owners to obtain a first-hand perspective.

Findings
This paper brings to light the rising trend toward homestays, the benefits of homestay tourism from the perspective of homestay stakeholders (both tourists and owners) and the impact on economic, social and cultural life, as a result of growth in the homestay concept.

Originality/value
The current level of discussion about homestays is limited, as there are relatively few prior studies reported in the literature.