bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single cell atlas of the neonatal small intestine with necrotizing enterocolitis
Authors: Egozi Adi , Olaloye Oluwabunmi , Werner Lael , Silva Tatiana , McCourt Blake , Pierce Richard W. , An Xiaojing , Wang Fujing , Chen Kong , Pober Jordan S. , Shoval Dror , Itzkovitz Shalev , Konnikova Liza 
Published: March 2022

AbstractNecrotizing enterocolitis (NEC) is a gastrointestinal complication of premature infants with high rates of morbidity and mortality. A comprehensive view of the cellular changes and aberrant interactions that underlie this disease is lacking. Here, we combine single cell RNA sequencing, T Cell Receptor beta (TCRβ) analysis, bulk transcriptomics, and imaging to characterize cell identities, interactions and zonal changes in NEC. We find that inflammatory macrophages are abundant in NEC and that T cells exhibit increased expression of inflammatory genes and cytokines accompanied by an increase in TCRβ clonal expansion. Fibroblasts and endothelial cells increase in proportion and exhibit a switch to an activated pro-inflammatory state. Villus tip epithelial cell identity is substantially reduced in NEC and the remaining epithelial cells up-regulate pro-inflammatory genes. We establish a detailed map of aberrant epithelial-mesenchymal-immune interactions that may be driving inflammation in NEC mucosa. Our analyses highlight the cellular changes underlying NEC disease pathogenesis and identify potential targets for biomarker discovery and therapeutics.
Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period
Authors: Yu Esther Dawen , Narowski Tara M. , Wang Eric , Garrigan Emily , Mateus Jose , Frazier April , Weiskopf Daniela , Grifoni Alba , Premkumar Lakshmanane , da Silva Antunes Ricardo , Sette Alessandro 
Published: March 2022

AbstractUnderstanding immune memory to Common Cold Coronaviruses (CCCs) is relevant for assessing its potential impact on the outcomes of SARS-CoV-2 infection, and for the prospects of pan-corona vaccines development. We performed a longitudinal analysis, of pre-pandemic samples collected from 2016-2019. CD4+ T cells and antibody responses specific for CCC and to other respiratory viruses, and chronic or ubiquitous pathogens were assessed. CCC-specific memory CD4+ T cells were detected in most subjects, and their frequencies were comparable to those for other common antigens. Notably, responses to CCC and other antigens such as influenza and Tetanus Toxoid (TT) were sustained over time. CCC-specific CD4+ T cell responses were also associated with low numbers of HLA-DR+CD38+ cells and their magnitude did not correlate with yearly changes in the prevalence of CCC infections. Similarly, spike RBD-specific IgG responses for CCC were stable throughout the sampling period. Finally, high CD4+ T cell reactivity to CCC, but not antibody responses, was associated with high pre-existing SARS-CoV-2 immunity. Overall, these results suggest that the steady and sustained CCC responses observed in the study cohort are likely due to a relatively stable pool of CCC-specific memory CD4+ T cells instead of fast decaying responses and frequent reinfections.
ECD of PepT1 interacts with TM1 to facilitate substrate transport
Authors: Shen Jiemin , Hu Miaohui , Ren Zhenning , Fan Xiao , Portioli Corinne , Yan Xiuwen , Rong Mingqiang , Zhou Ming 
Published: March 2022

AbstractMammalian peptide transporters, PepT1 and PepT2, mediate uptake of a wide variety of di- and tri-peptides and are essential for the absorption of dietary peptides in the digestive tract and the recovery of peptides in renal filtrate. PepT also mediates absorption of many drugs and prodrugs to enhance their bioavailability. PepT has 12 transmembrane (TM) helices that fold into two domains, the N-terminal domain (NTD, TM1-6) and C-terminal domain (CTD, TM7-12), and a large extracellular domain (ECD) of ∼200 amino acids between TM9 and TM10. It is known that peptide transport involves large motions of the N- and C-domains, but the role of ECD remains unclear. Here we report the structure of PepT1 from Equus caballus (horse) determined by cryo-electron microscopy. The structure shows that ECD interacts with TM1 and bridges the N- and C-domains. Deletion of the ECD or mutations to the TM1-ECD interface both impair the transport activity. These results demonstrate a role of ECD in structure and function of PepT1 and enhance our understanding of the mechanism of transport in PepT1.
Persisting decreases in state and trait anxiety post-psilocybin: A naturalistic, observational study among retreat attendees
Authors: Kiraga M.K. , Kuypers K. P. C. , Uthaug M. V. , Ramaekers J.G. , Mason N. L. 
Published: March 2022

AbstractAnxiety disorders are the most common type of psychiatric disorders among Western countries. Evidence-based treatment modalities including pharmacological and cognitive-behavioral therapy result in relatively low response rates (average range: 51 - 58%). Historical and recent research suggests psychedelic drugs may be efficacious in alleviating anxiety-related symptoms among healthy and clinical populations. The main aim of the present study was investigation of the effects of psilocybin-containing truffles, when taken in a supportive group setting, on ratings of state and trait anxiety across self-reported healthy volunteers. Attendees of psilocybin ceremonies were asked to complete a test battery at three separate occasions: before the ceremony (baseline), the morning after, and one week after the ceremony. The test battery included questionnaires assessing state and trait anxiety (State-Trait Anxiety Inventory), mindfulness capacities (Five Facet Mindfulness Questionnaire), and personality (Big Five Inventory). Additionally, the psychedelic experience was quantified with the Persisting Effects Questionnaire and the Ego Dissolution Inventory. The total amount of psilocybin-containing truffles consumed by each participant was recorded, and a sample of the truffles was analyzed to determine psilocin concentrations. Fifty-two attendees (males= 25; females= 25; others= 2) completed parts of the baseline assessment, 46 (males= 21; females= 24; others= 1) completed assessments the morning after the ceremony, and 23 (males= 10; females= 13) completed assessments at the one-week follow-up. Average psilocin consumption across individuals was 27.1 mg. We observed medium to large reductions in anxiety measures (both state and trait) compared to baseline which persisted over a one-week period post-ceremony. At one week post-ceremony, the non-judging facet of the mindfulness scale was increased, while the personality trait neuroticism decreased, when compared to baseline. Additionally, we found neuroticism and ratings of ego dissolution to be the strongest predictors of reductions in trait and state anxiety, respectively. In sum, results indicate rapid and persisting (up to one week) anxiolytic effects in psilocybin retreat attendees, which are related to the acute experience of ego dissolution, as well as lasting changes in trait neuroticism. To understand whether these effects extend to wider populations suffering from heightened anxiety, and the mechanisms involved, further experimental research is needed.
The conserved genetic program of male germ cells uncovers ancient regulators of human spermatogenesis
Authors: Correia Rion Brattig , Almeida Joana M. , Wyrwoll Margot J. , Julca Irene , Sobral Daniel , Misra Chandra Shekhar , Persio Sara Di , Guilgur Leonardo G. , Schuppe Hans-Christian , Silva Neide , Prudêncio Pedro , Nóvoa Ana , Leocádio Ana S. , Bom Joana , Laurentino Sandra , Mallo Moisés , Kliesch Sabine , Mutwil Marek , Rocha Luis M. , Tüttelmann Frank , Becker Jörg D. , Navarro-Costa Paulo 
Published: March 2022

SummaryMale germ cells share a common origin across animal species, therefore they likely retain a conserved genetic program that defines their cellular identity. However, the unique evolutionary dynamics of male germ cells coupled with their widespread leaky transcription pose significant obstacles to the identification of the core spermatogenic program. Through network analysis of the spermatocyte transcriptome of vertebrate and invertebrate species, we describe the conserved evolutionary origin of metazoan male germ cells at the molecular level. We estimate the average functional requirement of a metazoan male germ cell to correspond to the expression of approximately 10,000 protein-coding genes, a third of which defines a genetic scaffold of deeply conserved genes that has been retained throughout evolution. Such scaffold contains a set of 79 functional associations between 104 gene expression regulators that represent a core component of the conserved genetic program of metazoan spermatogenesis. By genetically interfering with the acquisition and maintenance of male germ cell identity, we uncover 161 previously unknown spermatogenesis genes and three new potential genetic causes of human infertility. These findings emphasize the importance of evolutionary history on human reproductive disease and establish a cross-species analytical pipeline that can be repurposed to other cell types and pathologies.
Antiviral and Neuroprotective Abilities of Influenza Virus Infection in Tractable Brain Organoids
Authors: Zhang Xiaodong , Lin Haishuang , Dong Liangzhen , Xia Qing 
Published: March 2022

AbstractHuman pluripotent stem cell (hPSC)-derived brain organoids offer an unprecedented opportunity for various applications as an in vitro model, such as modeling virus infection and drug screening. In this study, we present an experimental brain organoid platform for modeling infection with multiple viruses (e.g., influenza virus or enterovirus). Brain organoids challenged by influenza viruses (H1N1-WSN and H3N2-HKT68) had decreased overall organoid size, similar to ZIKA virus infection, while enteroviruses (EV68 and EV71) infected brain organoids displayed the opposite result. Then, we studied the molecular events in WSN-infected organoids, and we found that WSN could widely infect multiple cell types, and preferentially infected MAP2+ neurons compared to SOX2+ neural stem cells (NSCs) and GFAP+ astrocytes in brain organoids, and induced apoptosis of NSCs and neurons, but not astrocytes. The inflammatory responses in organoids observed to occur (Tumor necrosis factor alpha, interferon gamma, and interleukin 6) after WSN infection may further facilitate brain damage. Furthermore, transcriptional profiling revealed several upregulated genes (CSAG3 and OAS2) and downregulated genes (CDC20B, KCNJ13, OTX2-AS1, CROCC2, and F5) after WSN infection for 24 hpi and 96 hpi, implicating antiviral drugs development responses to WSN. Finally, we explored neurotrophic factors (e.g., BDNF, GDNF, and NT3) and PYC-12 as antiviral and neuroprotective reagents, which could significantly suppress virus infection, apoptosis, and inflammatory responses. Collectively, we established a tractable experimental model system to investigate the impact and mechanism of virus infection on human brain development, and provide a platform for rapidly screening therapeutic compounds, advancing the development of antiviral strategies.
High Calcium Transport by Polycystin-2 (TRPP2) Induces Channel Clustering and Coordinated Oscillatory Behavior
Authors: Velázquez Irina F. , Cantiello Horacio F. , del Rocío Cantero María 
Published: March 2022

AbstractThe regulation by Ca2+ of Ca2+-permeable ion channels represents an important mechanism in the control of cell function. Polycystin-2 (PC2, TRPP2), a member of the TRP channel family (Transient Potential Receptor), is a Ca2+ permeable non-selective cation channel. Previous studies from our laboratory demonstrated that physiological concentrations of Ca2+ do not regulate in vitro translated PC2 (PC2iv) channel activity. However, the issue as to PC2’s Ca2+ permeability and regulation remain ill-defined. In this study, we assessed Ca2+ transport by PC2iv, in a lipid bilayer reconstitution system in the presence of a high Ca2+ gradient (CaCl2 100 mM cis, CaCl2 10 mM trans). PC2iv channel reconstitution was conducted in the presence of either 3:7 or 7:3 1-palmitoyl-2-oleoyl-choline (POPC) and ethanolamine (POPE) lipid mixtures. Reconstituted PC2iv showed spontaneous Ca2+ currents, in both lipid mixtures with a maximum conductance of 63 ± 13 pS (n = 19) and 105 pS ± 9.8 (n = 9), respectively. In both cases, experimental data were best fitted with the Goldman-Hodgkin-Katz equation, showing a reversal potential (Vrev ~ −27 mV) consistent with strict Ca2+ selectivity. The R742X mutated PC2 (PC2R742X), lacking the carboxy terminal domain of the channel showed no differences with wild type PC2. Interestingly, spontaneous Ca2+ current oscillations were observed whenever PC2-containing samples were reconstituted in the 3:7, but not 7:3 POPC:POPE lipid mixture. The amplitude and frequency of the oscillations were highly dependent on the applied voltage, the imposed Ca2+ gradient, and the presence of high Ca2+, which induced PC2 channel clustering as observed by atomic force microscopy (AFM). We also used the QuB suite to kinetically model the PC2 channel Ca2+ oscillations based on the presence of subconductance states in the channel. The encompassed data provide new evidence to support a high Ca2+ permeability by PC2, and a novel regulatory feedback mechanism dependent on the presence of Ca2+ and phospholipids on its function.Statement of SignificanceThe regulation by Ca2+ of Ca2+-permeable ion channels represents an important mechanism in the control of cell function. The Transient Potential Receptor channel Polycystin-2 (TRPP2, PC2), is a Ca2+ permeable non-selective cation channel. Ca2+ transport by PC2 has largely been inferred by changes in reversal potential. This study provides experimental evidence on the Ca2+-transporting capabilities of PC2 in high Ca2+ that is modulated by lipids and generates a novel phenomenon of oscillatory currents by channel clustering and multiple subconductance behavior. PC2 can be self-regulated by feedback mechanisms, which are independent of external regulatory proteins. This oscillatory behavior, previously unknown for a single channel species, depend on the presence of Ca2+ interaction sites as have been postulated for the channel protein.
What drives wolf preference towards wild ungulates? Insights from a multi-prey system in the Slovak Carpathians
Authors: Guimarães Nuno F. , Álvares Francisco , Ďurová Jana , Urban Peter , Bučko Jozef , Iľko Tomáš , Brndiar Jaro , Štofik Jozef , Pataky Tibor , Barančeková Miroslava , Kropil Rudolf , Smolko Peter 
Published: March 2022

AbstractThe wolf is a generalist-opportunistic predator that displays diverse and remarkably adaptable feeding strategies across its range with local adaptations to certain prey species depending on their availability and vulnerability. The multi-prey system of the Slovak Carpathians supports important portion of the European wolf population; however, it has been markedly understudied. We evaluated winter diet composition and prey selection of Slovak wolves based on 321 scat samples collected between September – February within four different study areas during 2015 – 2017. The winter diet of wolves in the Slovak Carpathians was characterized by a 98% occurrence of wild large-sized and medium-sized ungulates with red deer occurring in wolf scats most often, consistent with their highest density among other wild ungulates. However, by comparing the consumption with availability of wild prey, we found that wolves in fact selected for wild boar especially in areas with higher altitudinal range, while selected for red deer in areas with low altitudinal range where this prey species was more spatially predictable. Although wolves showed the potential to switch between red deer and wild boar when their density increases, we found that this variation can be rather linked to changing prey vulnerability, which is dependent on particular environmental conditions at local scale such as topography and snow accumulation. The present study provides valuable insights into the winter foraging ecology of Slovak wolves in a multi-prey system of the Carpathians and allows for practical implications in the management of the rapidly increasing populations of wild ungulates across Europe.
Proton-driven alternating access in a spinster transporter, an emerging family of broad-specificity efflux pumps
Authors: Dastvan Reza , Rasouli Ali , Dehghani-Ghahnaviyeh Sepehr , Gies Samantha , Tajkhorshid Emad 
Published: March 2022

AbstractSpinster (Spns) lipid transporters are critical for transporting sphingosine-1-phosphate (S1P) across cellular membranes. In humans, Spns2 functions as the main S1P transporter in endothelial cells, making it a potential drug target for modulating S1P signaling. Here, we employed an integrated approach in lipid membranes to identify unknown conformational states of a bacterial Spns from Hyphomonas neptunium (HnSpns) and to define its proton- and substrate-coupled conformational dynamics. Our systematic study reveals conserved residues critical for protonation steps and their regulation, and how sequential protonation of these proton switches coordinates the conformational transitions in the context of a noncanonical ligand-dependent alternating access. A conserved periplasmic salt bridge (Asp60TM2:Arg289TM7) keeps the transporter in a closed conformation, while proton-dependent conformational dynamics are significantly enhanced on the periplasmic side, providing a pathway for ligand exchange. Furthermore, our resistance assays reveal substrate polyspecificity and HnSpns multidrug resistance (MDR) activity that underscore the previously unknown role of Spns proteins in MDR, beyond their activity in sphingolipid transport and signaling.
6DOF nonlinear control loading system for a large transport aircraft simulator
Authors: Amir Ahmadi Chomachar Saeb , Kuppusamy Ashok 
Published: March 2022

Purpose
Flight simulators are one of the noticeable breakthroughs in aerospace engineering. One of the main compartments of flight simulators is its control loading system (CLS). The CLS functions as a generator of virtual aerodynamic control-loads over control columns of a simulator. This paper aims to present the design of a high-fidelity six six degrees of freedom (6DOF) nonlinear CLS for the Boeing-747 aircraft simulator.

Design/methodology/approach
An introduction to CLS for flight motion simulators are first recapitulated. Afterward, the commanding devices are explained through schematics available in an engineering sense. This paper then presents in detail, the active control loading strategy and hardware design for the CLS, while also introducing the aerodynamic model structure. The satisfactory computer numerical simulations are presented before the paper ends up in concluding remarks.

Findings
The multiple input multiple output (MIMO) 6DOF nonlinear CLS for Boeing-747 flight simulator has been successfully developed. The outcome of computer simulations in real-time verifies practicality of the design strategy. The research presented in this paper could be a simple roadmap for prototyping high-fidelity 6DOF nonlinear CLS for flight motion simulators.

Originality/value
The available control architecture and hardware technologies cannot enable a high-fidelity load realization in a CLS. The existing research has not yet presented a 6DOF nonlinear MIMO CLS architecture along with the underlying controller setup for a high-fidelity load realization. In this paper, the design of a high-fidelity 6DOF nonlinear MIMO CLS for flight simulator of a large transport aircraft has been accomplished.
Emergency health in the aftermath of disasters: a post-Hurricane Matthew skin outbreak in rural Haiti
Authors: Cela Toni , Marcelin Louis Herns , Fleurantin Nadia Lise , Jean Louis Shesly 
Published: March 2022

PurposeThe purpose of this paper is to analyze the context of the emergence of a skin infection outbreak in the aftermath of Hurricane Matthew in Haiti and detail the role of community-based participatory research in mobilizing local action in a country with low state capacity.Design/methodology/approachWhile implementing a post-disaster study that combined a survey of 984 households and 69 community leaders with 23 focus groups, 60 ethnographic interviews and community mapping, a skin infection outbreak was detected. Using study results, the research team in partnership with different stakeholders responded to the outbreak with a health intervention.FindingsThe findings illustrate how pre-existing conditions shape local communities' vulnerability to health crises in the aftermath of disasters and the critical role research can play in informing the recovery processes. Community-based approaches to emergency health reinforced by multi-stakeholder partnerships with local government can strengthen post-disaster response and governance structures setting the groundwork for the development of local resilience.Research limitations/implicationsThe health intervention was implemented as a result of the study. Patients served were not derived from the study sample but were self-selected based on their need for skin-related medical treatment.Originality/valueThis article highlights the integral role research can play in identifying the health impacts of disaster events in vulnerable, hard-to-reach communities and strengthening government involvement in disaster governance.
Understanding subcontracting organizational arrangements for construction projects in China: integrating capabilities and uncertainty
Authors: Shi Chenxi , Chen Yongqiang , Hua Yuanyuan , Tang Yinqiu 
Published: March 2022

PurposeChinese construction projects commonly implement subcontracting, but organizational arrangements have received little attention. Some studies have debated the impact of firm capabilities on subcontracting. To address these issues, this study differentiates the general contractor’s technological capabilities and alliance management capabilities and investigates how capabilities affect the degree of subcontracting and subcontracting dispersion based on the resource-based view and transaction cost economics.Design/methodology/approachBy conducting a survey, 219 valid questionnaires were collected from Chinese construction companies. Multiple regression analyses were conducted to test the influence of capabilities on subcontracting organizational arrangements and the moderating role of uncertainty.FindingsThe results show that technological capabilities decrease the degree of subcontracting, whereas alliance management capabilities increase the degree of subcontracting as well as subcontracting dispersion. The results also indicate that the positive effects of alliance management capabilities are weakened by project uncertainty.Practical implicationsThis study provides a better understanding of the diversity of subcontracting organizational arrangements in China. In addition, the findings may help general contractors carry out a rational arrangement by considering their capabilities and transaction hazards.Originality/valueThis study contributes to a holistic understanding of how capabilities determine subcontracting by distinguishing technological capabilities and alliance management capabilities and refining the degree of subcontracting and subcontracting dispersion. Meanwhile, the findings highlight the complementarity of the resource-based view and transaction cost economics by examining the moderating effect of uncertainty.