bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coenzyme Q regulates UCP1 expression and thermogenesis through the integrated stress responses
Authors: Chang Ching-Fang , Gunawan Amanda L. , Zushin Peter-James H. , Timblin Greg A. , Bertholet Ambre M. , Wang Biao , Sajio Kaoru , Kirichok Yuriy , Stahl Andreas 
Published: March 2022

AbstractCoenzyme Q (CoQ) is an essential component of mitochondrial respiration1 and required for thermogenic activity in brown adipose tissues2 (BAT). CoQ deficiency leads to a wide range of pathological manifestations3 but mechanistic consequences of CoQ deficiency in specific tissues such as BAT remain poorly understood. Here we show that pharmacological or genetic CoQ deficiency (50-75% reduction) in BAT leads to accumulation of cytosolic mitochondrial RNAs (mtRNAs) and activation of the eIF2α kinase PKR resulting in the induction of the integrated stress response (ISR) and suppression of UCP1 expression in an ATF4-dependent fashion. Surprisingly, despite diminished UCP1 levels, BAT CoQ deficiency increases whole-body metabolic rates at room temperature and thermoneutrality resulting in decreased weight gain on high fat diets (HFD). This mitohormesis like effect of BAT CoQ insufficiency is dependent on the ATF4-FGF21 axis in BAT revealing an unexpected role for CoQ in the modulation of whole-body energy expenditure with wide-ranging implications for primary and secondary CoQ deficiencies.
A South American mouse morbillivirus sheds light into a clade of rodent-borne morbilliviruses
Authors: Debat Humberto J. 
Published: March 2022

AbstractMorbilliviruses are negative sense single stranded monosegmented RNA viruses in the family Paramyxoviridae (order Mononegavirales). Morbilliviruses infect diverse mammals including humans, dogs, cats, small ruminants, seals, and cetaceans, which serve as natural hosts. Here, I report the identification and characterization of novel viruses associated with South American long-haired and olive field mice. The divergent viruses dubbed Ratón oliváceo morbillivirus (RoMV) detected in renal samples from mice collected from Chile and Argentina are characterized by an unusually large genome including long intergenic regions and the presence of an accessory protein between the F and H genes redounding in a genome architecture consisting in 3’-N-P/V/C-M-F-hp-H-L-5’. Structural and functional annotation, genetic distance and evolutionary insights suggest that RoMV is a member of a novel species within genus Morbillivirus tentatively dubbed South American mouse morbillivirus. Phylogenetic analysis suggests that this mouse morbillivirus is closely related to, and clusters into a monophyletic group of novel rodent-borne morbilliviruses. This subclade of divergent viruses expands the host range, redefines the genomic organization and provides insights on the evolutionary history of genus Morbillivirus.
A Biological Signature for the Inhibition of Outer Membrane Lipoprotein Biogenesis
Authors: Lehman Kelly M. , Smith Hannah C. , Grabowicz Marcin 
Published: March 2022

ABSTRACTThe outer membrane (OM) of Gram-negative bacteria is an essential organelle that acts as a formidable barrier to antibiotics. Increasingly prevalent resistance to existing drugs has exacerbated the need for antibiotic discovery efforts targeting the OM. Acylated proteins, known as lipoproteins, are essential in every pathway needed to build the OM. The central role of OM lipoproteins makes their biogenesis a uniquely attractive therapeutic target, but it also complicates in vivo identification of on-pathway inhibitors, as inhibition of OM lipoprotein biogenesis broadly disrupts OM assembly. Here, we use genetics to probe the eight essential proteins involved in OM lipoprotein biogenesis. We define a biological signature consisting of three simple assays that can characteristically identify OM lipoprotein biogenesis defects in vivo. The few known chemical inhibitors of OM lipoprotein biogenesis conform to the biological signature. We also examine MAC13243, a proposed inhibitor of OM lipoprotein biogenesis, and find that it fails to conform to the biological signature. Indeed, we demonstrate that MAC13243 activity relies entirely on a target outside of the OM lipoprotein biogenesis pathway. Hence, our signature offers simple tools to easily assess whether antibiotic lead compounds target an essential pathway that is the hub of OM assembly.IMPORTANCEGram-negative bacteria have an outer membrane, which acts as a protective barrier and excludes many antibiotics. The limited number of antibiotics active against Gram-negative bacteria, along with rising rates of antibiotic resistance, highlights the need for efficient antibiotic discovery efforts. Unfortunately, finding the target of lead compounds, especially ones targeting outer membrane construction, remains difficult. The hub of outer membrane construction is the lipoprotein biogenesis pathway. We show that defects in this pathway result in a signature cellular response that can be used to quickly and accurately validate pathway inhibitors. Indeed, we found that MAC13243, a compound previously proposed to target outer membrane lipoprotein biogenesis, does not fit the signature, and we show that it instead targets an entirely different cellular pathway. Our findings offer a streamlined approach to discovery and validation of lead antibiotics against a conserved and essential pathway in Gram-negative bacteria.
TheVerticillium longisporumphospholipase VlsPLA2is a virulence factor targets host nuclei and modulates plant immunity
Authors: Rafiei Vahideh , Vélëz Heriberto , Piombo Edoardo , Dubey Mukesh , Tzelepis Georgios 
Published: March 2022

AbstractPhospholipases A2(PLA2) are lipolytic enzymes, responsible for phospholipids hydrolysis. The role of PLA2in various aspects of cell physiology has been shown, but their involvement in host-microbe interactions remains to be elucidated. The present study investigated the biological function of the secreted VIsPLA2phospholipase in the phytopathogenic fungusVerticillium longisporumwith emphasis on its role in host-microbe interactions. TheVlsPLA2was highly induced inV. longisporumduring interaction with host plantBrassica napus, encoding an active phospholipase A2. VlsPLA2-overexpressionV. longisporumstrain showed an increased virulence onArabidopsisplants, plausibly by inducing virulence factors. Furthermore, VIsPLA2are transported to the nucleus, by hijacking VAMPA proteins, causing suppression of PTI-induced hypersensitive response, possibly by modulating the expression of genes involved in plant immunity. In summary, VlsPLA2acts as a virulence factor by hydrolyzing the hosts nuclear envelope phospholipids, an action that induces signaling cascade, suppressing basal plant immunity responses.
Shallow environmental gradients can cause range margins to form
Authors: Tomasini Matteo , Eriksson Martin , Johannesson Kerstin , Rafajlović Marina 
Published: March 2022

AbstractOne hypothesis invoked to explain limits to species’ ranges is a mismatch in environmental conditions between the central and marginal areas of species’ ranges. Low population size at the margins causes genetic drift to outplay selection locally, and limits the accumulation of genetic variance, so that adaptation is hindered locally. Earlier theoretical work shows that, for a population expanding over a spatially heterogeneous environment without any geographical barriers, adaptation will fail abruptly and sharp range margins will establish only when the underlying environmental conditions change more and more severely across space, whereas an environment changing constantly will result either in infinite expansion or rapid global extinction. Here, we extend this “steepening-gradient hypothesis” to encompass situations when multiple (up to three) environmental factors impose selection on separate adaptive traits. We show that multiple selection gradients steepen each other and that it is sufficient that just one of the gradients steepen in space for sharp range margins to form. This is true even if this gradient is shallow throughout the realised range. Thus, despite its detrimental role in forming range margins, it could be overlooked in field studies. Finally, by decomposing an environmental gradient to selection on two (or three) adaptive traits, we show that a population can withstand harsher environmental conditions than when selection acts on one adaptive trait alone. This finding argues for the evolution of novel traits in harsh environments.
The genome wide analysis deciphered virulence factors and secondary metabolites of Chryseobacterium and description of Chryseobacterium indicum sp. nov
Authors: Victor Manish Prakash , Das Lipika , Das Subrata K. 
Published: March 2022

ABSTRACTThis study describes a novel bacterium, Chryseobacterium strain PS-8, isolated from the skin of freshwater pufferfish (Tetraodon cutcutia). Cells are Gram-negative. The genome size is 4.72 Mb, and the G+C content is 36.4%. The in silico DDH homology, ANI, and AAI were below the cutoff value, 70% and 95% to 96%, respectively, as required for novel species delineation. The phylogenomic analysis using core and non-recombinant core genes, the strain PS-8 showed clustering with Chryseobacterium gambrini DSM 18014T. Generally, Chryseobacterium species are considered opportunistic pathogens. Prediction of the virulence genes revealed genes for adherence, biofilm and stability (glf, lpxD, clpE, cps0, clpE, IlpA), proliferation (tufA, cap8E, galE, kfic, bioB, clpP, kdtB, csgD, carB), resistance to immune response (htpB, katA, wbtl, sodB, kpsF), and host-defense evasion system (kpst, clpE, kfic, ybtQ, cap8G, clpP). The cladogram based upon the virulence genes showed a similar phylogeny amongst the Chryseobacterium species. Additionally, secondary metabolites producing gene clusters were identified, including microviridin, resorcinol and polyene, terpene, etc. Our study showed that strain PS-8 constitute a novel species for which Chryseobacterium indicum sp. nov. is proposed. The type strain is PS-8T (= TBRC 15233T = NBRC 115235T).
Multifaceted Atlases of the Human Brain in its Infancy
Authors: Ahmad Sahar , Wu Ye , Wu Zhengwang , Thung Kim-Han , Lin Weili , Li Gang , Wang Li , Yap Pew-Thian 
Published: March 2022

ABSTRACTBrain atlases agglomerate structural and functional features of a population of individuals in a standard coordinate space. Here, we introduce for the first time a collection of atlases that charts postnatal development of the human brain in a spatio-temporally dense manner from two weeks to two years of age. Atlases capturing month-to-month changes of the human brain are essentially nonexistent for the first two years of life — the critical developmental period during which the brain is evolving in virtually all facets at an exponential pace. This unmet need is compounded by the lack of atlases that provide a unified and holistic picture of the brain from both the perspectives of cortical surface convolutions and tissue volumetric characteristics. Existing surface and volumetric atlases are typically constructed independently in different coordinate spaces, causing discrepancies and complications in multifaceted analyses. Our month-specific conjoint surface and volumetric atlases chart normative patterns and capture key traits of early brain development and are therefore critical for identifying aberrations from normal developmental trajectories. Our atlases represent a major advance toward providing the neuroscience community an invaluable resource to facilitate the understanding of early structural and functional development by mapping multiple measurements of infant brains in a common reference frame for precise spatio-temporal quantification of cortical and subcortical changes.
Accurate Protein Domain Structure Annotation with DomainMapper
Authors: Manriquez-Sandoval Edgar , Fried Stephen D. 
Published: March 2022

SUMMARYAutomated domain annotation plays a number of important roles in structural informatics and typically involves searching query sequences against Hidden Markov Model (HMM) profiles. This process can be ambiguous or inaccurate when proteins contain domains with non-contiguous residue ranges, and especially when insertional domains are hosted within them. Here we present DomainMapper, an algorithm that accurately assigns a unique domain structure annotation to any query sequence, including those with complex topologies. We validate our domain assignments using the AlphaFold database and confirm that non-contiguity is pervasive (6.5% of all domains in yeast and 2.5% in human). Using this resource, we find that certain folds have strong propensities to be non-contiguous or insertional across the Tree of Life, likely underlying evolutionary preferences for domain topology. DomainMapper is freely available and can be run as a single command line function.HIGHLIGHTSDomainMapper generates a unique domain structure annotation, including non-contiguous and insertional domainsAutomated annotations of non-contiguous domains are validated against the AlphaFold databaseDomainMapper can be easily installed and used by non-expertsCertain folds have strong preferences to be non-contiguous or insertionalGRAPHICAL ABSTRACT
ASD modelling in organoids reveals imbalance of excitatory cortical neuron subtypes during early neurogenesis
Authors: Jourdon Alexandre , Wu Feinan , Mariani Jessica , Capauto Davide , Norton Scott , Tomasini Livia , Amiri Anahita , Suvakov Milovan , Schreiner Jeremy D. , Jang Yeongjun , Panda Arijit , Nguyen Cindy Khanh , Cummings Elise M. , Han Gloria , Powell Kelly , Szekely Anna , McPartland James C. , Pelphrey Kevin , Chawarska Katarzyna , Ventola Pamela , Abyzov Alexej , Vaccarino Flora M. 
Published: March 2022

SummaryThere is no clear genetic etiology or convergent pathophysiology for autism spectrum disorders (ASD). Using cortical organoids and single-cell transcriptomics, we modeled alterations in the formation of the forebrain between sons with idiopathic ASD and their unaffected fathers in thirteen families. Alterations in the transcriptome suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between the excitatory neurons of the dorsal cortical plate and other lineages such as the early-generated neurons from the putative preplate. The imbalance stemmed from a divergent expression of transcription factors driving cell fate during early cortical development. While we did not find probands’ genomic variants explaining the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and developmental transcriptome in idiopathic ASD.
Attracting the millennial customer: the case of food trucks
Authors: Kraus Sascha , Sen Sandipan , Savitskie Katrina , Kumar Sampath K. , Brooks John 
Published: March 2022

PurposeThe purpose of this paper is to examine millennial customer perceptions of food trucks and to identify factors that can foster their behavioral intentions pertaining to food trucks.Design/methodology/approachThe study is based on a sample of 247 millennial customers of various food truck vendors in the United States and was assessed using ordinary least squares regression analysis.FindingsFood truck image and employee friendliness were found to impact both customer satisfaction and word of mouth behavior; however, the other hypotheses were not supported.Research limitations/implicationsThere were two limitations. The first was that one of the constructs did not achieve the minimum average variance extracted. The second was that data collection was done in a single city in the United States; therefore, future research could overcome these limitations through a refinement of the construct’s items and targeting more cities.Originality/valueThere has been limited academic research on the millennial customer perceptions of the food truck phenomenon. This research addresses that gap through a field study that examines factors that contributed to the growth and popularity of food trucks among millennials
Potential role of general practice in reducing emergency department demand: A qualitative study
Authors: Willson Katie A , Lim David , Toloo Ghasem‐Sam , FitzGerald Gerry , Kinnear Frances B , Morel Douglas G 
Published: March 2022

AbstractObjectiveTo inform local, state and national strategies intended to reduce demand for ED care, the present study aimed to identify key factors influencing the current provision of acute care within primary healthcare (PHC) and explore the policy and system changes potentially required.MethodsSemi‐structured interviews with key stakeholders were audio‐recorded, transcribed verbatim and analysed through content and thematic approaches incorporating the Walt and Gilson health policy framework.ResultsEleven interviews were conducted. Five key considerations were highlighted, namely the barriers and enablers for general practitioners (GPs) in providing acute care, barriers to patient use of PHC instead of ED, suggestions for new PHC models and improvements for current ED models. Additionally, economic issues relating to clinic funding and GP remuneration, complexities of state or federal funding and management of urgent care centres (UCC) were identified. Potential policy changes included GP clinics incorporating emergency appointments, GP triage, further patient streaming and changes to the ED medical workforce model, as well as linking hospitals with PHC clinics. Suggested system changes included improving rapid access to non‐GP specialists, offering qualifications for urgent care within PHC, developing integrated information technology systems and educating patients regarding appropriate healthcare system pathways.ConclusionThe present study suggested that while PHC has the potential to attenuate the demands for ED services, a whole‐of‐system approach focusing on realignment of priorities and integrated changes are needed.
Relative contribution of genetic and environmental factors to determination of wing morphs of the brown planthopper Nilaparvata lugens
Authors: Zhang Chao , Mao Meng‐Sha , Liu Xiang‐Dong 
Published: March 2022

AbstractWing dimorphism is a fascinating feature of the ability of insects to adapt to environments. The brown planthopper (BPH) Nilaparvata lugens, a serious pest of rice, can switch between the long‐ and short‐winged morphs. It has been known that environmental factors can affect the wing morph of BPH. However, it is still unclear whether the effect of environment is dependent on BPH genetic backgrounds or not. In the present study, we established the pure‐bred lineages of short‐ and long‐winged BPHs via multigenerational selection, and we found that survival and fecundity were similar between these 2 lineages. Wing morphs of the pure‐bred lineages were almost fully dependent on genetics, but independent of the environmental factors, nymphal density and rice plant stage, 2 key factors affecting BPH wing morphs. In the unselected BPH population, short‐ and long‐winged morphs were produced depending on those 2 environmental factors, indicating the contribution of environment to wing morph. In the wing‐selected lineages, 4 developmental regulated genes of wing, NlInR1, NlInR2, NlAkt, and NlFoxo were expressed stably in the short‐winged adults, but almost silenced in the long‐winged adults. However, all these genes were expressed normally with a similar level in both the short‐ and long‐winged adults in an unselected population except NlFoxo. The pure‐bred lineages of long‐ and short‐winged morphs exhibited different expression patterns of wing development‐regulated genes, suggesting the genetic determination of wing morphs. Effects of environmental factors on wing morphs occurred only in the genetic mix population.
From being sacked to being unwell: A conservation of resources view on the effects of psychological contract violation on layoff victims' wellbeing
Authors: Asante Eric Adom , Oduro Frederick , Danquah Barbara , Dei Mensah Rebecca , Dartey‐Baah Kwasi , Affum‐Osei Emmanuel 
Published: March 2022

AbstractAlthough there is a consensus in the literature that layoff can be viewed as a form of psychological contract (PC) violation, research is yet to examine how such violation impacts layoff victims' well‐being outcomes including life satisfaction, sleep quality and psychological distress. Integrating psychological contract theory and the conservation of resource theory, we hypothesized a dual‐stage moderated mediation model in which PC violation resulting from layoff is associated with three dimensions of layoff victims' well‐being via worry. This indirect effect is proposed to be conditional on the level of social support received. Based on a sample of 252 layoff victims, we found support for the dual‐stage moderated mediation model in which the association between PC violation and the three dimensions of well‐being via worry was weak for layoff victims reporting high levels of social support. Findings contribute to our understanding of how PC violation is associated with nonwork outcomes.
Giving sleep position advice in pregnancy: Will we make women anxious?
Authors: Warland Jane , Footner Sarah , Beaufoy Georgie , Stocker Jade , Agostini Alex , Dorrian Jillian 
Published: March 2022

BackgroundThere is now robust evidence that when women settle to sleep on their back in late pregnancy (>28 weeks) they are at increased risk of stillbirth. Therefore, there are several stillbirth prevention programs worldwide that have begun advising pregnant women to adopt a side position when settling to sleep in late pregnancy. However, some hold concerns that giving women information about sleep position and stillbirth risk may make them anxious.AimThis study aimed to determine what influences how ‘safe sleep’ messages are perceived by pregnant women and if there is anxiety associated with receiving this message.Materials and MethodsAn online survey of 537 Australian women (n = 97 were ‘currently pregnant’). The survey examined participant’s views regarding sleep position messages, type of information source as well as participant characteristics such as general anxiety and their fetal health locus of control (FHLC).ResultsOur findings suggest that the FHLC may influence how health messaging regarding sleep in pregnancy is perceived and acted upon. We have also shown a subset of pregnant women may feel anxiety associated with the sleep position in pregnancy message. This may not be related to history of anxiety, but rather to their higher ‘internal’ FHLC, ie those who reflect a greater sense of personal agency over fetal health.ConclusionsOur findings suggest most women will perceive information about settling into sleep position as informative rather than anxiety provoking. Therefore, maternity care providers should not be overly concerned about provoking anxiety when providing this information.