bluuebunny/crossref_metadata_2025_split huggingface dataset:
When the microbiome defines the host phenotype: selection on vertical transmission in varying environments
Authors: Bruijning Marjolein , Henry Lucas P. , Forsberg Simon K.G. , Metcalf C. Jessica E. , Ayroles Julien F. 
Published: September 2020

AbstractThe microbiome can contribute to variation in fitness-related traits of their hosts, and thus to host evolution. Hosts are therefore expected to be under selection to control their microbiome, for instance through controlling microbe transmission from parents to offspring. Current models have mostly focused on microbes that either increase or decrease fitness. In that case, host-level selection is relatively straightforward, favouring either complete or no inheritance. In natural systems, however, vertical transmission fidelity varies widely, and microbiome composition is often shaped by a combination of vertical and horizontal transmission modes. We propose that such mixed transmission could optimize host fitness under fluctuating environments. Using a general model, we illustrate that decreasing vertical transmission fidelity increases the amount of microbiome variation, and thus potentially phenotypic variation, across hosts. Whether or not this is advantageous depends on environmental conditions, how much the microbiome changes during host development, and the contribution of other factors to trait variation. We discuss how environmentally-dependent microbial effects can favor intermediate transmission, review examples from natural systems, and suggest research avenues to empirically test our predictions. Overall, we show that imperfect transmission may be adaptive by allowing individuals to ensure phenotypic variability in their offspring in contexts where varying environments mean that this strategy increases long-term fitness.
Induction of a regulatory myeloid program in bacterial sepsis and severe COVID-19
Authors: Reyes Miguel , Filbin Michael R. , Bhattacharyya Roby P. , Sonny Abraham , Mehta Arnav , Billman Kianna , Kays Kyle R. , Pinilla-Vera Mayra , Benson Maura E. ,   MGH COVID-19 Collection & Processing Team, Cosimi Lisa A. , Hung Deborah T. , Levy Bruce D. , Villani Alexandra-Chloe , Sade-Feldman Moshe , Baron Rebecca M. , Goldberg Marcia B. , Blainey Paul C. , Hacohen Nir 
Published: September 2020

AbstractA recent estimate suggests that one in five deaths globally are associated with sepsis1. To date, no targeted treatment is available for this syndrome, likely due to substantial patient heterogeneity2,3and our lack of insight into sepsis immunopathology4. These issues are highlighted by the current COVID-19 pandemic, wherein many clinical manifestations of severe SARS-CoV-2 infection parallel bacterial sepsis5–8. We previously reported an expanded CD14+ monocyte state, MS1, in patients with bacterial sepsis or non-infectious critical illness, and validated its expansion in sepsis across thousands of patients using public transcriptomic data9. Despite its marked expansion in the circulation of bacterial sepsis patients, its relevance to viral sepsis and association with disease outcomes have not been examined. In addition, the ontogeny and function of this monocyte state remain poorly characterized. Using public transcriptomic data, we show that the expression of the MS1 program is associated with sepsis mortality and is up-regulated in monocytes from patients with severe COVID-19. We found that blood plasma from bacterial sepsis or COVID-19 patients with severe disease induces emergency myelopoiesis and expression of the MS1 program, which are dependent on the cytokines IL-6 and IL-10. Finally, we demonstrate that MS1 cells are broadly immunosuppressive, similar to monocytic myeloid-derived suppressor cells (MDSCs), and have decreased responsiveness to stimulation. Our findings highlight the utility of regulatory myeloid cells in sepsis prognosis, and the role of systemic cytokines in inducing emergency myelopoiesis during severe bacterial and SARS-CoV-2 infections.
Deletion of intestinal SHP impairs short-term response to cholic acid challenge in mice
Authors: Nguyen James T , Riessen Ryan R , Zhang Tongyu , Kieffer Colin , Anakk Sayeepriyadarshini 
Published: September 2020

AbstractSmall heterodimer partner (SHP) is a crucial regulator of bile acid (BA) transport and synthesis; however, its intestine-specific role is not fully understood. Here, we report that Intestine-specificShpknockout (IShpKO) mice have higher intestinal and hepatic BAs, but not serum BAs when challenged with an acute (5-day) 1% cholic acid (CA) diet. Consistent with this finding, BA synthetic genesCyp7A1andCyp8b1are not repressed to the same extent inIShpKOcompared to control mice post-CA challenge. Loss of intestinal SHP did not alterFxrαmRNA but increasedAsbt(BA ileal uptake transporter) andOstα(BA ileal efflux transporter) expression even under chow-fed conditions. Surprisingly, the acute CA diet inIShpKOdid not elicit the expected induction ofFgf15but was able to maintain the suppression ofAsbt, andOstα/βmRNA levels. At the protein level, ASBT was downregulated, while OSTα/β expression was induced and maintained regardless of diet. Examination of ileal histology inIShpKOmice challenged with acute CA diet revealed reduced villus length and goblet cell numbers. However, no difference in goblet cell number, villus morphology, crypt depth, and the expression of BA regulator and transporter genes was seen betweenf/f ShpandIShpKOmice after chronic (14-day) CA diet suggesting an adaptive response. We found the upregulation of thePparα-Ugtaxis, which can reduce the BA burden and compensate for the ileal SHP function. Thus, our study reveals that ileal SHP expression contributes to both overall intestinal structure and BA homeostasis.
Sunday driver mediates multi-compartment Golgi outposts defects induced by amyloid precursor protein
Authors: Du Qianqian , Chang Jin , Cheng Guo , Zhao Yinyin , Zhou Wei 
Published: September 2020

AbstractGolgi defects including Golgi fragmentation are pathological features of Alzheimer’ disease (AD). As a pathogenic factor of AD, amyloid precursor protein (APP) induces Golgi fragmentation in soma. However, how APP regulates Golgi outposts (GOs) in dendrites remains unclear. Given that APP resided and affected GOs movements, especially reversed the distribution of multi-compartment GOs (mcGOs), we investigated the regulatory mechanism of mcGOs movements inDrosophilalarvae. Knockdown experiments showed the bidirectional mcGOs movements were cooperatively controlled by dynein heavy chain (Dhc) and kinesin heavy chain subunits. Notably, only Dhc mediated APP’s regulation on mcGOs movements. Further, by loss-of-function screening, the adaptor protein Sunday driver (Syd) was identified to mediate APP-induced alteration of the direction of mcGOs movements, and dendritic defects. Collectively, by elucidating a model of bidirectional mcGOs movements, we revealed the mechanism of APP’s regulation on the direction of mcGOs movements. It provides new insights into AD pathogenesis.
Deploying a novel tuberculosis molecular bacterial load assay to assess the elimination rate ofMycobacterium tuberculosisin patients with multidrug-resistant tuberculosis in Tanzania
Authors: Mbelele Peter M. , Mpolya Emmanuel A. , Sauli Elingarami , Mtafya Bariki , Ntinginya Nyanda E. , Addo Kennedy K. , Kreppel Katharina , Mfinanga Sayoki , Phillips Patrick P.J. , Gillespie Stephen H. , Heysell Scott K. , Sabiiti Wilber , Mpagama Stellah G. 
Published: September 2020

AbstractBackgroundRifampin or multidrug-resistant-tuberculosis (RR/MDR-TB) treatment has transitioned to injectable-free regimens. We tested whetherM. tuberculosis(Mtb) elimination rates measured by molecular bacterial load assay (TB-MBLA) in sputa correlate with composition of the RR/MDR-TB antibiotic regimen.MethodsSerial sputa were collected from patients with RR/MDR- and drug-sensitive TB at day 0, 3, 7, 14, and then monthly for 4 months of anti-TB treatment. TB-MBLA was used to quantify viableMtb16S rRNA in sputum for estimation of colony-forming-unit per mL (eCFU/mL).Mtbelimination rates were compared among regimens using nonlinear-mixed-effects modeling of repeated measures.ResultsAmong 37 patients with a total of 296 serial sputa; 7 patients received rifampin/isoniazid/pyrazinamide/ethambutol (RHZE), 8 an all-oral bedaquiline-based regimen, 9 an injectable and bedaquiline-containing regimen, and 13 an injectable-containing but bedaquiline-free regimen. The overall mean dailyMtbelimination was −0.24 [95% Confidence-Interval (CI); −0.39 to −0.08)] log10eCFU/mL, and it varied with treatment-regimen (p < 0.001). Compared to the adjustedMtbelimination of −0.17 (95% CI; −0.23 to −0.12) for the injectable-containing but bedaquiline-free reference regimen, the elimination rates were −0.62 (95% CI; −1.05 to −0.20) log10eCFU/mL for the injectable and bedaquiline-containing regimen (p = 0.019), −0.35 (95% CI; −0.65 to −0.13) log10eCFU/mL for the all-oral bedaquiline-based regimen (p = 0.054), and −0.29 (95% CI; −0.78 to +0.22) log10eCFU/mL for RHZE (p = 0.332)ConclusionTB-MBLA distinguishedMtbelimination rates in sputa from patients receiving different treatment regimens, suggesting a reliable monitoring tool for RR/MDR-TB, that does not require mycobacterial culture.
Inhaled corticosteroid use in COVID-19
Authors: Husby Anders , Pottegård Anton , Hviid Anders 
Published: September 2020

ABSTRACTBackgroundRecent evidence has established a beneficial effect of systemic corticosteroids for treatment of moderate-to-severe COVID-19. However, it is unknown if inhaled corticosteroid use is associated with reduced morbidity of the disease.MethodsIn a nationwide cohort of hospitalized SARS-CoV-2 test-positive individuals in Denmark, we estimated the 30-day hazard ratio of intensive care unit (ICU) admission or death among users of inhaled corticosteroids (ICS) compared with users of non-ICS inhalers (β2-agonist/muscarinic-antagonists), or non-users of ICS, with Cox regression adjusted for age, sex, and other confounders. We repeated these analyses among influenza test-positive patients during 2010–2018.ResultsAmong 2,180 hospitalized SARS-CoV-2 patients, 282 were admitted to ICU and 421 died within 30 days. ICS use was associated with a hazard ratio of 1.25 (95% CI [CI], 0.60 to 2.61) for ICU admission and 0.84 (95% CI, 0.54 to 1.31) for death compared with non-ICS inhaler use. Compared with no ICS use, the hazard ratio of ICU admission or death was 1.22 (95% CI, 0.77 to 1.94) and 1.05 (95% CI, 0.75 to 1.47), respectively. Among 10,279 hospitalized influenza patients, the hazard ratios were 1.43 (95% CI, 0.89 to 2.30) and 1.11 (95% CI, 0.85 to 1.46) for ICU admission, and 0.80 (95% CI, 0.63 to 1.01) and 1.03 (95% CI, 0.87 to 1.22) for death compared with non-ICS inhaler use and no ICS use, respectively.ConclusionsOur results do not support an effect of inhaled corticosteroid use on COVID-19 morbidity, however we can only rule out moderate-to-large reduced or increased risks.
Training a neural network to learn other dimensionality reduction removes data size restrictions in bioinformatics and provides a new route to exploring data representations
Authors: Dexter Alex , Thomas Spencer A. , Steven Rory T. , Robinson Kenneth N. , Taylor Adam J. , Elia Efstathios , Nikula Chelsea , Campbell Andrew D. , Panina Yulia , Najumudeen Arafath K. , Murta Teresa , Yan Bin , Grabowski Piotr , Hamm Gregory , Swales John , Gilmore Ian S. , Yuneva Mariia O. , Goodwin Richard J.A. , Barry Simon , Sansom Owen J. , Takats Zoltan , Bunch Josephine 
Published: September 2020

AbstractHigh dimensionality omics and hyperspectral imaging datasets present difficult challenges for feature extraction and data mining due to huge numbers of features that cannot be simultaneously examined. The sample numbers and variables of these methods are constantly growing as new technologies are developed, and computational analysis needs to evolve to keep up with growing demand. Current state of the art algorithms can handle some routine datasets but struggle when datasets grow above a certain size. We present a training deep learning via neural networks on non-linear dimensionality reduction, in particular t-distributed stochastic neighbour embedding (t-SNE), to overcome prior limitations of these methods.One Sentence SummaryAnalysis of prohibitively large datasets by combining deep learning via neural networks with non-linear dimensionality reduction.
Lions and brown bears colonized North America in multiple synchronous waves of dispersal across the Bering Land Bridge
Authors: Salis Alexander T , Bray Sarah C E , Lee Michael S Y , Heiniger Holly , Barnett Ross , Burns James A , Doronichev Vladimir , Fedje Daryl , Golovanova Liubov , Harington C Richard , Hockett Bryan , Kosintsev Pavel , Lai Xulong , Mackie Quentin , Vasiliev Sergei , Weinstock Jacobo , Yamaguchi Nobuyuki , Meachen Julie , Cooper Alan , Mitchell Kieren J 
Published: September 2020

AbstractThe Bering Land Bridge connecting North America and Eurasia was periodically exposed and inundated by oscillating sea levels during the Pleistocene glacial cycles. This land connection allowed the intermittent dispersal of animals, including humans, between Western Beringia (far north-east Asia) and Eastern Beringia (north-west North America), changing the faunal community composition of both continents. The Pleistocene glacial cycles also had profound impacts on temperature, precipitation, and vegetation, impacting faunal community structure and demography. While these paleoenvironmental impacts have been studied in many large herbivores from Beringia (e.g., bison, mammoths, horses), the Pleistocene population dynamics of the diverse guild of carnivorans present in the region are less well understood, due to their lower abundances. In this study, we analyze mitochondrial genome data from ancient brown bears (Ursus arctos; n = 103) and lions (Pantheraspp.; n = 39), two megafaunal carnivorans that dispersed into North America during the Pleistocene. Our results reveal striking synchronicity in the population dynamics of Beringian lions and brown bears, with multiple waves of dispersal across the Bering Land Bridge coinciding with glacial periods of low sea levels, as well as synchronous local extinctions in Eastern Beringia during Marine Isotope Stage 3. The evolutionary histories of these two taxa underscore the crucial biogeographic role of the Bering Land Bridge in the distribution, turnover, and maintenance of megafaunal populations in North America.
Phenotypic and functional characterisation of first trimester human placental macrophages, Hofbauer cells
Authors: Thomas Jake , Appios Anna , Zhao Xiaohui , Dutkiewicz Roksana , Donde Maria , Lee Colin , Naidu Praveena , Lee Christopher , Cerveira Joana , Liu Bing , Ginhoux Florent , Burton Graham , Hamilton Russell S. , Moffett Ashley , Sharkey Andrew , McGovern Naomi 
Published: September 2020

AbstractHofbauer cells (HBC) are a population of macrophages found in high abundance within the stroma of the first trimester human placenta. HBC are the only fetal immune cell population within the stroma of healthy placenta. However, the functional properties of these cells are poorly described. Aligning with their predicted origin via primitive haematopoiesis, we find that HBC are transcriptionally similar to yolk sac macrophages. Phenotypically, HBC can be identified as HLA-DR-FOLR2+macrophages. We identify a number of factors HBC secrete (including IL-8 and MMP-9) that could affect placental angiogenesis and remodelling. We determine that HBC have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal. Finally, we also identify a population of placenta-associated maternal macrophages (PAMM1a) that adhere to the placental surface and express factors, such as fibronectin, that may aid in repair.SummaryUsing transcriptomic and proteomic data, Thomas, J. et al, analyse human first trimester placental macrophages and delineate markers that identify them. They also reveal that Hofbauer cells have microbicidal capacity, providing the fetus with an additional layer of protection from certain microbes.One sentence summaryHofbauer cells are primitive placental macrophages with a unique phenotype and role in fetal defence.Non-standard abbreviationPlacental associated maternal monocytes/macrophages, PAMM.
Sleep-specific changes in physiological brain pulsations
Authors: Helakari H , Korhonen V , Holst SC , Piispala J , Kallio M , Väyrynen T , Huotari N , Raitamaa L , Tuunanen J , Kananen J , Järvelä M , Raatikainen V , Borchardt V , Kinnunen H , Nedergaard M , Kiviniemi V 
Published: September 2020

AbstractSleep is known to increase the convection of interstitial brain metabolites along with cerebrospinal fluid (CSF). We used ultrafast magnetic resonance encephalography (MREGBOLD) to quantify the effect of sleep on physiological (vasomotor, respiratory and cardiac) brain pulsations driving the CSF convection in humans. Transition to electroencephalography verified sleep occurred in conjunction with power increase and reduced spectral entropy (SE) of physiological brain pulsations. During sleep, the greatest increase in spectral power was in very-low frequency (VLF < 0.1 Hz) waves, followed by respiratory and cardiac brain pulsations. SE reduction coincided with decreased vigilance in awake state and could robustly (ROC 0.88, p < 0.001) differentiate between sleep vs. awake states, indicating the sensitivity of SE of the MREGBOLDsignal as a marker for sleep level. In conclusion, the three physiological brain pulsation contribute to the sleep-associated increase in glymphatic CSF convective flow in an inverse frequency order.HighlightsBrain tissue contains almost no connective tissue, this enabling pressure waves to initiate long-distance brain pulsationsBrain pulsations are induced by vasomotion, respiration, and the cardiac cycleSleep strikingly increases spectral power and decreases spectral entropy of brain pulsations, especially for the very low frequency vasomotor wavesSpectral entropy of brain pulsations detected by MREG is a sensitive measure of vigilance, resembling the corresponding entropy changes detected by scalp EEG
The potential function of forehead gland secretions in conflict resolution of the male Great Himalayan leaf-nosed bats
Authors: Zhang Chunmian , Sun Congnan , Lucas Jeffrey R. , Gu Hao , Feng Jiang , Jiang Tinglei 
Published: September 2020

AbstractChemical communication is an important aspect of social behavior in almost all animals. Here, we used gas chromatography-mass spectrometry (GC-MS) to detect the chemical composition, and behavioral tests to evaluate the potential function of forehead gland secretions between adult male Great Himalayan leaf-nosed bats,Hipposideros armiger. Our results showed that the concentrations of compounds and their categories differed significantly among individuals, and behavioral studies indicated that males are capable of utilizing the secretions for individual discrimination. Moreover, paired males that were incapable of gland protrusion showed more physical contact and longer contest duration compared to pairs in which both males could protrude the gland. In trials where only one male could protrude the gland, males with gland protrusion were more likely to win in contests. These findings provide the first behavioral evidence that chemical communication plays a vital role in conflict resolution in non-human mammals.
When things go wrong: the implications for facilitators of work integrated learning placements in international destinations
Authors: Agnew Deborah , Abery Elizabeth , Schulz Sam , Pill Shane 
Published: September 2020

PurposeInternational work integrated learning (iWIL) placements for university students are widely promoted within universities. However, they cannot be offered and sustained without a great deal of time and effort; most commonly the responsibility of an assigned university facilitator. Preparation and support are essential for a positive student experience and iWIL outcome. However, not all experiences and outcomes are positive, or predictable.Design/methodology/approachPersonal vignettes of university iWIL facilitators are used to create a collaborative autoethnography (CAE) of experiences and outcomes where placements have been affected by unexpected or unprecedented “critical incidents” and the impact incurred on these academics. The vignettes are analyzed according to the Pitard (2016) six-step structural analysis model.FindingsAnalysis of the vignettes identifies a resulting workload cost, emotional labor and effect on staff wellbeing. Due to the responsibility and expectations of the position, these incidents placed the university iWIL facilitator in a position of vulnerability, stress, added workload and emotional labor that cannot be compared to other academic teaching roles.Practical implicationsIt is intended through the use of “real life” stories presented in the vignettes, to elicit consideration and recognition of the role of the iWIL facilitator when dealing with “the negatives” and “bring to light” management and support strategies needed.Originality/valueResearch is scant on iWIL supervisor experience and management of “critical incidents”, therefore this paper adds to the literature in an area previously overlooked.
Home-based telework: usefulness and facilitators
Authors: Ollo-López Andrea , Goñi-Legaz Salomé , Erro-Garcés Amaya 
Published: September 2020

PurposeThis article aims to analyze individual-, organizational- and country-level factors that determine the use of home-based telework across Europe according to the technology acceptance model (TAM) and the technology–organization–environment model.Design/methodology/approachTo examine the impact of individual-, organizational- and country-level factors on telework, multilevel models are estimated to prevent problems derived from biased standard errors when micro- and macro-level data are combined.FindingsThe main findings show that, according to the usefulness side of the TAM, employees with family responsibilities, those that live away from their work and highly qualified workers use more home-based telework. Additionally, and according to the ease of use side of the TAM, empowerment in firms facilitates home-based telework. At the country level, lower power distance, individualism and femininity, better telework regulations and technology developments are also facilitators of home-based telework.Research limitations/implicationsThe study is limited by the cross-sectional nature of the data. This prevents the estimation of causal effects. Additional research would benefit from the use of panel data and from a more detailed analysis of the effects of country dimensions.Practical implicationsFrom an applied perspective, politics related to cultural dimensions are suggested to stimulate home-based telework.Originality/valueThe research contributes to previous literature by: (1) considering a large sample to conduct an empirical analysis of the use of home-based telework across Europe, (2) including micro and macro factors, (3) providing a theoretical framework to explain home-based telework, (4) applying a rigorous definition of home-based telework and (5) focusing on employees who are able to adopt home-based telework.