bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomics of Bronchoalveolar Lavage Cells Identifies New Molecular Endotypes of Sarcoidosis
Authors: Vukmirovic Milica , Yan Xiting , Gibson Kevin F. , Gulati Mridu , Schupp Jonas C. , DeIuliis Giuseppe , Adams Taylor S. , Hu Buqu , Mihaljinec Antun , Woolard Tony , Lynn Heather , Emeagwali Nkiruka , Herzog Erica L. , Chen Edward S. , Morris Alison , Leader Joseph K. , Zhang Yingze , Garcia Joe G. N. , Maier Lisa A. , Colman Ron , Drake Wonder P. , Becich Michael , Hochheiser Harrison , Wisniewski Steven R. , Benos Panayiotis V. , Moller David R. , Prasse Antje , Koth Laura L. , Kaminski Naftali 
Published: July 2020

ABSTRACTSarcoidosis is a multisystem granulomatous disease of unknown origin with a variable and often unpredictable course and pattern of organ involvement. In this study we sought to identify specific bronchoalveolar lavage (BAL) cell gene expression patterns indicative of distinct disease phenotypic traits.RNA sequencing by Ion Torrent Proton was performed on BAL cells obtained from 215 well characterized patients with pulmonary sarcoidosis enrolled in the multicenter Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Weighted Gene Co-expression Network Analysis (WGCNA) and non-parametric statistics were used to analyze genome wide BAL transcriptome. Validation of results was performed using a microarray expression data set of an independent sarcoidosis cohort (Freiburg, Germany (n=50)).Our supervised analysis found associations between distinct transcriptional programs and major pulmonary phenotypic manifestations of sarcoidosis including; TH1 and TH17 pathways associated with hilar lymphadenopathy; TGFB1 and MTOR signaling with parenchymal involvement, and IL7 and IL2 with airway involvement. Our unsupervised analysis revealed gene modules that uncovered four potential sarcoidosis endotypes including hilar lymphadenopathy with increased acute T cell immune response; extraocular organ involvement with PI3K activation pathways; chronic and multiorgan disease with increased immune response pathways; and multiorgan with increased IL-1 and IL-18 immune and inflammatory responses. We validated the occurrence of these endotypes using gene expression, pulmonary function tests and cell differentials from Freiburg. Taken together our results identify BAL gene expression programs that characterize major pulmonary sarcoidosis phenotypes and suggest the presence of distinct disease molecular endotypes.Take home messageGenome wide BAL transcriptomics identified novel gene expression profiles associated with distinct phenotypic traits in sarcoidosis and is suggestive of the presence of novel molecular and clinical sarcoidosis endotypes that could help with further understanding of this heterogenous disease.
Spatial and temporal context jointly modulate the sensory response within the ventral visual stream
Authors: He Tao , Richter David , Wang Zhiguo , de Lange Floris P. 
Published: July 2020

AbstractBoth spatial and temporal context play an important role in visual perception and behavior. Humans can extract statistical regularities from both forms of context to help processing the present and to construct expectations about the future. Numerous studies have found reduced neural responses to expected stimuli compared to unexpected stimuli, for both spatial and temporal regularities. However, it is largely unclear whether and how these forms of context interact. In the current fMRI study, thirty-three human volunteers were exposed to object stimuli that could be expected or surprising in terms of their spatial and temporal context. We found a reliable independent contribution of both spatial and temporal context in modulating the neural response. Specifically, neural responses to stimuli in expected compared to unexpected contexts were suppressed throughout the ventral visual stream. Interestingly, the modulation by spatial context was stronger in magnitude and more reliable than modulations by temporal context. These results suggest that while both spatial and temporal context serve as a prior that can modulate sensory processing in a similar fashion, predictions of spatial context may be a more powerful modulator in the visual system.Significance StatementBoth temporal and spatial context can affect visual perception, however it is largely unclear if and how these different forms of context interact in modulating sensory processing. When manipulating both temporal and spatial context expectations, we found that they jointly affected sensory processing, evident as a suppression of neural responses for expected compared to unexpected stimuli. Interestingly, the modulation by spatial context was stronger than that by temporal context. Together, our results suggest that spatial context may be a stronger modulator of neural responses than temporal context within the visual system. Thereby, the present study provides new evidence how different types of predictions jointly modulate perceptual processing.
Long non-coding RNA regulation of spermatogenesis and endosomal processes via the spectrin cytoskeleton inDrosophila
Authors: Bouska Mark J , Bai Hua 
Published: July 2020

ABSTRACTThe spectrin cytoskeleton has been shown to be critical in diverse processes such as axon development and degeneration, myoblast fusion, and spermatogenesis. Spectrin can be modulated in a tissue specific manner through junctional protein complexes, however, it has not been shown that lncRNAs interact with and regulate spectrin. Here we provide evidence of a lncRNA that interacts with α and β Spectrin to regulate spermatogenesis and endosomal related activity in fat bodies ofDrosophila. Protein-RNA and Protein-Protein biochemical analysis indicated the interaction between α and β Spectrin is modulated by the lncRNA CR45362. Immunocytochemistry revealed CR45362 is highly expressed in the basal testis while α and β Spectrin are clearly disrupted in this same region of CR45362 mutants. We genetically demonstrate α-Spectrin and CR45362 deficiencies cause spermatid nuclear bundling defects with congruous changes of spectrin distribution and reduced Lysotracker staining in the fat body. Our data suggests lncRNA regulation of spectrin could provide cells with a repertoire of modulatory molecules to manipulate cell-type specific cytoskeletal and endosomal requirements.
Species detection within theEchinococcus granulosus sensu latocomplex by novel probe-based Real-Time PCRs
Authors: Maksimov Pavlo , Bergmann Hannes , Wassermann Marion , Romig Thomas , Gottstein Bruno , Casulli Adriano , Conraths Franz J. 
Published: July 2020

AbstractInfections with eggs ofEchinococcus granulosus sensu lato(s.l.) can cause cystic echinococcosis in intermediate host animals and humans. Upon ingestion of viable eggs, oncospheres hatch from the eggs and subsequently develop into fluid-filled larval cysts, most frequently in the liver or the lungs. The slowly growing cysts progressively interfere with organ function. The risk of infection is determined by the host range of the parasite, its pathogenicity and other epidemiologically relevant parameters, which differ significantly among the five species within theE. granulosus s.l. complex. It is therefore essential to diagnose the correct species withinE. granulosus s.l. to help understand specific disease epidemiology and to facilitate effective implementation of control measures. For this purpose, simple, fast and cost-effective typing techniques are needed.We developed quantitative Real-Time Polymerase Chain Reactions (qPCRs) and corresponding sequence-specific hydrolysis DNA probes to target polymorphic regions in the mitochondrial genome ofE. granulosus s.l.. In a single-step typing approach, we distinguishedE. granulosus s.l. members in four epidemiologically relevant subgroups. These wereE. granulosus sensu stricto(G1, G3),E. equinus(G4),E. ortleppi(G5) and theE. canadensiscluster (G6 to G8 and G10). The technique also allowed identification and differentiation of these species from otherEchinococcusorTaeniataxa for samples isolated from cysts or faeces.Single-step genotyping techniques for the molecular diagnosis ofEchinococcusspp. by qPCRs may not only improve diagnostic performance, but also our knowledge on the epidemiology of the parasites and help controlling the various agents of cystic echinococcosis.
Functional mapping of B-cell linear epitopes of SARS-CoV-2 in COVID-19 convalescent population
Authors: Yi Zhigang , Ling Yun , Zhang Xiaonan , Chen Jieliang , Hu Kongying , Wang Yuyan , song Wuhui , Ying Tianlei , Zhang Rong , Lu Hongzou , Yuan Zhenghong 
Published: July 2020

AbstractPandemic SARS-CoV-2 has infected over 10 million people and caused over 500,000 mortalities. Vaccine development is in urgent need to stop the pandemic. Despite great progresses on SARS-CoV-2 vaccine development, the efficacy of the vaccines remains to be determined. Deciphering the interactions of the viral epitopes with their elicited neutralizing antibodies in the convalescent COVID-19 population inspires the vaccine development. In this study, we devised a peptide array composed of 20-mer overlapped peptides of spike (S), membrane (M) and envelope (E) proteins, and performed a screening with 120 COVID-19 convalescent serums and 24 non-COVID-19 serums. We identified five SARS-CoV-2-specific dominant epitopes that reacted with above 40% COVID-19 convalescent serums. Epitopes in the receptor-binding domain (RBD) of S ill reacted with the convalescent serums. Of note, two peptides non-specifically interacted with most of the non-COVID-19 serums. Neutralization assay indicated that only five serums completely blocked viral infection at the dilution of 1:200. By using a peptide-compete neutralizing assay, we found that three dominant epitopes partially competed the neutralization activity of several convalescent serums, suggesting antibodies elicited by these epitopes played an important role in neutralizing viral infection. The epitopes we identified in this study may serve as vaccine candidates to elicit neutralizing antibodies in most vaccinated people or specific antigens for SARS-CoV-2 diagnosis.
Inhibitory and Transport Mechanisms of the Human Cation-Chloride Cotransport KCC1
Authors: Zhao Yongxiang , Shen Jiemin , Wang Qinzhe , Zhou Ming , Cao Erhu 
Published: July 2020

SummarySecondary active cation-chloride cotransporters (CCCs) catalyze electroneutral symport of Cl−with Na+and/or K+across membranes1,2. CCCs are fundamental in cell volume homeostasis, transepithelia ion movement, maintenance of intracellular Cl−concentration, and inhibitory synaptic transmission3–6. K+-Cl−cotransport 1 (KCC1) was first characterized in red blood cells and later in many other cell types as a crucial player in regulatory volume decrease in defense against cell swelling upon hypotonic challenges7,8. Here we present two cryo-EM structures of human KCC1: one captured in an inward-open state and another arrested in an outward-open state by a small molecule inhibitor. KCC1 can surprisingly adopt two distinct dimeric architectures via homotypic association of different protein domains and conversion between these two forms of dimers may entail dynamic formation and rupture of two interdigitating regulatory cytoplasmic domains. The inhibitor wedges into and forces open an extracellular ion permeation path and arrests KCC1 in an outward-open conformation. Concomitantly, the outward-open conformation involves inward movement of the transmembrane helix 8 and occlusion of the intracellular exit by a conserved short helix within the intracellular loop 1. Our structures provide a blueprint for understanding the mechanisms of CCC transporters and their inhibition by small molecule compounds.
High-content analysis reveals senescence of cultured canine adipose-derived mesenchymal stromal cells to be reversible with a novel immortalization approach
Authors: Stojiljković Ana , Gaschen Véronique , Forterre Franck , Rytz Ulrich , Stoffel Michael H. , Bluteau Jasmin 
Published: July 2020

1SummaryIn the last decades, the scientific community spared no effort to elucidate the therapeutic potential of mesenchymal stromal cells (MSCs). Unfortunately,in vitrocellular senescence occurring along with a loss of proliferative capacity is a major drawback in view of future therapeutic applications of these cells in the field of regenerative medicine. Even though insight into the mechanisms of replicative senescence in human medicine has evolved dramatically, knowledge about replicative senescence of canine MSCs is still scarce. Thus, we developed a high-content analysis workflow to simultaneously investigate three important characteristics of senescence in canine adipose-derived MSCs (cAD-MSCs): morphological changes, activation of the cell cycle arrest machinery and increased activity of the senescence-associated β-galactosidase. We took advantage of this tool to demonstrate that passaging of cAD-MSCs results in the appearance of a senescence phenotype and proliferation arrest. This was partially prevented upon immortalization of these cells using a newly designed PiggyBac™ Transposon System, which allows for the expression of the human polycomb ring finger proto-oncogene BMI1 and the human telomerase reverse transcriptase under the same promotor. Our results indicate that cAD-MSCs immortalized with this new vector maintain their proliferation capacity and differentiation potential for a longer time than untreated cAD-MSCs. This study not only offers a workflow to investigate replicative senescence in eukaryotic cells with a high-content analysis approach but also paves the way for a rapid and effective generation of immortalized MSC lines. This promotes a better understanding of these cells in view of future applications in regenerative medicine.
Structure of the HLTF HIRAN domain and its functional implications in regression of a stalled replication fork
Authors: Hishiki Asami , Sato Mamoru , Hashimoto Hiroshi 
Published: July 2020

HLTF (helicase-like transcription factor) is a yeast RAD5 homolog that is found in mammals. HLTF has E3 ubiquitin ligase and DNA helicase activities, and is a pivotal protein in template-switched DNA synthesis that allows DNA replication to continue even in the presence of DNA damage by utilizing a newly synthesized undamaged strand as a template. In addition, HLTF has a DNA-binding domain termed HIRAN (HIP116 and RAD5 N-terminal). HIRAN has been hypothesized to play a role in DNA binding; however, the structural basis of its role in DNA binding has remained unclear. In the past five years, several crystal structures of HIRAN have been reported. These structures revealed new insights into the molecular mechanism underlying DNA binding by HIRAN. Here, the structural information on HIRAN is summarized and the function of HIRAN in recognizing the 3′-terminus of the daughter strand at a stalled replication fork and the implications for its involvement in fork regression are discussed.
Understanding the implications of Belt and Road Initiative for sustainable supply chains: an environmental perspective
Authors: Butt Atif Saleem , Ali Imran 
Published: July 2020

PurposeThis research aims to explore the potential impacts of the Belt and Road Initiative (BRI) on sustainable supply chains.Design/methodology/approachThis study employs twenty qualitative interviews with supply chain managers located on the BRI lane from Asian countries.FindingsFindings revealed that if not managed properly, BRI can pose a serious threats to sustainable supply chains from environmental perspective. The findings also revealed additional properties which lead to the emergence of these perspective.Research limitations/implicationsThe findings of this study may not be generalizable to a broader population. Second, this study explores supply chain managers’ interpretations from Asian countries only.Practical implicationsSupply chain firms can use the findings from this study to understand the implications of BRI for sustainable supply chains. Particularly, firms can understand how the BRI may harm the organization's sustainable supply chains from the environmental perspective.Originality/valueThis is, perhaps, the first study which provides empirical evidence concerning the potential impacts of BRI on the management of sustainable supply chains.
Characterization of rotor losses in permanent magnet machines
Authors: Caunes Antomne , Takorabet Noureddine , Chaithongsuk Sisuda , Duranton Laurent 
Published: July 2020

Purpose
The purpose of this paper is to present a synthesis of the analysis and modeling of the rotor losses in high speed permanent magnets motors.

Design/methodology/approach
Three types of losses are as a result of eddy currents in the conductive parts of the rotor. The analysis includes their characterization and the setup of a numerical model using finite element method. The adopted methodology is based on the separation of the losses which allows a better understanding of the physical phenomena. Each type of losses will be modeled and computed separately.

Findings
It is possible to make a precise estimate of the different losses in the rotor while keeping a relatively short computing time.

Research limitations/implications
The analysis is applied on a high-speed permanent magnet motor for avionic application. The model is validated with the commercial finite element model (FEM) software Flux2D.

Originality/value
The developed model allows an important save in terms of CPU-time compared to commercial FEM software while staying accurate. The separation of each losses and their sources is important for motor engineers and was requested for them to improve the designs more easily.
A death in the family: a metaphor about race and police brutality
Authors: Avery Derek R. , Ruggs Enrica N. 
Published: July 2020

PurposeThis essay was written in response to the killings of George Floyd, Breonna Taylor and Rayshard Brooks by police in 2020 and the surge of social justice protests they helped to reignite.Design/methodology/approachThis essay uses a metaphor that nearly everyone can understand to help build common understanding around the unique impact of police killings of Black people on other Black people.FindingsThis essay uses social psychological theory and our experiences as Black Americans and diversity scholars to illustrate why interracial conversations about police killings of Black people may not proceed as intended.Originality/valueIn the wake of growing social justice protests aimed at combating systemic racism in the US, many individuals and organizations are wrestling with determining how people can talk about race. This is uncharted territory for many, as sociological research shows that racioethnic integration has stalled or even regressed in schools, workplaces and social networks in the US This essay seeks to help readers move toward a common understanding to facilitate more empathetic interracial interactions involving Black people in the aftermath of these traumatic experiences.
“The UK is not innocent”: Black Lives Matter, policing and abolition in the UK
Authors: Joseph–Salisbury Remi , Connelly Laura , Wangari-Jones Peninah 
Published: July 2020

PurposeThe purpose of this article is to show that racism is not only a US problem. Rather, racism is endemic and pervasive in the UK context, manifesting at every level of policing. From stop and search, to deaths after police contact, the authors highlight long-standing and widespread racist disparities in UK policing. The authors therefore pierce through any delusions of UK “post-racialism” in order to show that, as protesters have reminded us, “the UK is not innocent”.Design/methodology/approachIn this piece, the authors reflect on the Black Lives Matter protests of 2020. Whilst the catalyst was the death of George Floyd in the United States, the authors explore what the protests mean in the UK context. To do so, the authors draw upon recent high-profile examples of police racism, before situating those events within a wider landscape of racist policing.FindingsDemonstrating that UK policing has to be understood as institutionally racist, the authors suggest that responses to police racism need to be radical and uncompromising – tweaks to the system are not enough. The authors therefore look towards defunding and abolition as ways in which one can begin to seek change.Originality/valueThe piece takes up the challenges set by this Black Lives Matter moment and offers a critical take on policing that seeks to push beyond reformism whilst also highlighting the realities of UK racism.
About MyKindaFuture
Authors: Reichwald Simon 
Published: July 2020

PurposeThe purpose of this paper is to provide an overview of the changing and evolving apprenticeship market, with a specific focus on how it is beginning to impact the diversity of employer organisations across a range of industry sectors.Design/methodology/approachThis is an opinion piece, contextualising the UK business approach to apprenticeships and the levy. It includes case studies showing how the attraction and recruitment of apprentices have been used to address diversity issues in different organisations.FindingsEmployers are pushing for:A broader range of apprenticeship standards (and for them to be signed off more quickly),More of the UK population to be aware of the high-quality apprenticeship roles available,The necessary company infrastructure and appropriate external activities, to ensure that theBroadest range of talent applies for and secures apprentice roles.Partnership with the training provider(s) works well.Right level of support is in place for the apprentices, whether they are existing staff or new staff members (who are often young people, returners or ex-military).Line managers can quickly and effectively integrate apprentices into their teams, so that they are adding value and making an impact.
Workplace learning and organisational performance in the hospitality industry
Authors: Kleefstra Anne , Altan Michel , Stoffers Jol 
Published: July 2020

PurposeThe hospitality industry creates a distinctive context in which learning takes place. The industry's international perspective and large globalisation play an important role in learning, as well as the operational and structural features that give meaning to learning and development in the hospitality industry. This explorative research therefore studies the relation between workplace learning and organisational performance in the Dutch hospitality industry.Design/methodology/approachThe qualitative research is done through 15 in-depth interviews with general managers and HR managers of Dutch hotels with three or more stars and at least ten employees.FindingsIt can be concluded that there is a relation between workplace learning and organisational performance in the hospitality industry, as the participants in this research and the literature both mention workplace learning enhances organisational performance.Originality/valueLittle research has been done on learning and organisational performance specifically, in the (Western) hospitality industry. This research therefore focusses on HRD and studies the influence of workplace learning on organisational performance in the Dutch hospitality industry.