bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of singers’ masks on the impulse dispersion of aerosols during singing
Authors: Echternach Matthias , Herrmann Laila , Gantner Sophia , Tur Bogac , Peters Gregor , Westphalen Caroline , Benthaus Tobias , Köberlein Marie , Kuranova Liudmila , Döllinger Michael , Kniesburges Stefan 
Published: July 2021

AbstractBackgroundDuring the Covid-19 pandemic, singing activities were restricted due to several super-spreading events that have been observed during rehearsals and vocal performances. However, it has not been clarified how the aerosol dispersion, which has been assumed to be the leading transmission factor, could be reduced by masks which are specially designed for singers.Material and Methods12 professional singers (10 of the Bavarian Radio-Chorus and two freelancers, 7 females and 5 males) were asked to sing the melody of the ode of joy of Beethoven’s 9thsymphony “Freude schöner Götterfunken, Tochter aus Elysium” in D-major without masks and afterwards with five different singers’ masks, all distinctive in their material and proportions. Every task was conducted after inhaling the basic liquid from an e-cigarette. The aerosol dispersion was recorded by three high-definition video cameras during and after the task. The cloud was segmented and the dispersion was analyzed for all three spatial dimensions. Further, the subjects were asked to rate the practicability of wearing the tested masks during singing activities using a questionnaire.ResultsConcerning the median distances of dispersion, all masks were able to decrease the impulse dispersion of the aerosols to the front. In contrast, the dispersion to the sides and to the top was increased. The evaluation revealed that most of the subjects would reject performing a concert with any of the masks.ConclusionAlthough, the results exhibit that the tested masks could be able to reduce the radius of aerosol expulsion for virus-laden aerosol particles, there are more improvements necessary to enable the practical implementations for professional singing.
Nonlinear Functional Network Connectivity in Resting Fmri Data
Authors: Motlaghian S. M. , Belger A. , Bustillo J. R. , Ford J. M. , Lim K. , Mathalon D. H. , Mueller B. A. , O’Leary D. , Pearlson G. , Potkin S. G. , Preda A. , van Erp T.G. , Calhoun V. D. 
Published: July 2021

ABSTRACTIn this work, we focus on explicitly nonlinear relationships in functional networks. We introduce a technique using normalized mutual information (MI), that calculates the nonlinear correlation between different brain regions. We demonstrate our proposed approach using simulated data, then apply it to a dataset previously studied in (Damaraju et al., 2014). This resting-state fMRI data included 151 schizophrenia patients and 163 age- and gender-matched healthy controls. We first decomposed these data using group independent component analysis (ICA) and yielded 47 functionally relevant intrinsic connectivity networks. Our analysis showed a modularized nonlinear relationship among brain functional networks that was particularly noticeable in the sensory and visual cortex. Interestingly, the modularity appears both meaningful and distinct from that revealed by the linear approach. Group analysis identified significant differences in nonlinear dependencies between schizophrenia patients and healthy controls particularly in visual cortex, with controls showing more nonlinearity in most cases. Certain domains, including cognitive control, and default mode, appeared much less nonlinear, whereas links between the visual and other domains showed evidence of substantial nonlinear and modular properties. Overall, these results suggest that quantifying nonlinear dependencies of functional connectivity may provide a complementary and potentially important tool for studying brain function by exposing relevant variation that is typically ignored.Further, we propose a method that captures both linear and nonlinear effects in a ‘boosted’ approach. This method increases the sensitivity to group differences in comparison to the standard linear approach, at the cost of being unable to separate linear and nonlinear effects.
Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema
Authors: Khamissi Fatima Zohra , Ning Liang , Kefaloyianni Eirini , Dun Hao , Arthanarisami Akshayakeerthi , Keller Amy , Atkinson Jeffrey J. , Li Wenjun , Wong Brian , Dietmann Sabine , Lavine Kory , Kreisel Daniel , Herrlich Andreas 
Published: July 2021

AbstractMultiorgan failure is devastating, and its mechanisms and mediators are not clear. Tissue injury in one organ appears to trigger disease in remote organs. Kidney and lung are frequently affected, such as when acute kidney injury (AKI) causes acute lung injury (ALI), a frequent clinical condition with high mortality. Here we identify factors secreted from the injured kidney that cause acute lung injury. We developed a murine model mimicking the generation of respiratory failure following acute kidney injury. To identify interorgan crosstalk mediators involved, we performed scRNAseq of mouse kidneys and lungs after AKI. We then applied ligand-receptor (L-R) pairing analysis across cells residing in kidney (ligands) or lung (receptors) to identify kidney-released circulating osteopontin (OPN) as a novel mediator of AKI-induced ALI (AKI-ALI). OPN release very early after AKI largely from tubule cells triggered neutrophil and macrophage infiltration into lungs associated with endothelial leakage, interstitial edema, and functional impairment. Pharmacological or genetic inhibition of OPN prevented AKI-ALI. Transplantation of ischemicwtkidneys intowtmice caused AKI-ALI, while transplantation of ischemic OPN-global-knockout kidneys failed to induce lung endothelial leakage and AKI-ALI, identifying circulating kidney-released OPN as sufficient to cause AKI-ALIin vivo. We show that AKI in humans results in elevations in OPN levels in the serum. Increased serum OPN levels in patients with multiorgan failure have been shown to positively correlate with reduced kidney function, respiratory failure, and mortality. Thus, our results identifying OPN as a mediator of AKI-ALI may have important therapeutic implications in human AKI-ALI and multiorgan failure.
CoVizu: Rapid analysis and visualization of the global diversity of SARS-CoV-2 genomes
Authors: Ferreira Roux-Cil , Wong Emmanuel , Gugan Gopi , Wade Kaitlyn , Liu Molly , Baena Laura Muñoz , Chato Connor , Lu Bonnie , Olabode Abayomi S. , Poon Art F. Y. 
Published: July 2021

ABSTRACTPhylogenetics has played a pivotal role in the genomic epidemiology of SARS-CoV-2, such as tracking the emergence and global spread of variants, and scientific communication. However, the rapid accumulation of genomic data from around the world — with over two million genomes currently available in the GISAID database — is testing the limits of standard phylogenetic methods. Here, we describe a new approach to rapidly analyze and visualize large numbers of SARS-CoV-2 genomes. Using Python, genomes are filtered for problematic sites, incomplete coverage, and excessive divergence from a strict molecular clock. All differences from the reference genome, including indels, are extracted using minimap2, and compactly stored as a set of features for each genome. For each Pango lineage (https://cov-lineages.org), we collapse genomes with identical features into ‘variants’, generate 100 bootstrap samples of the feature set union to generate weights, and compute the symmetric differences between the weighted feature sets for every pair of variants. The resulting distance matrices are used to generate neigihbor-joining trees in RapidNJ and converted into a majority-rule consensus tree for the lineage. Branches with support values below 50% or mean lengths below 0.5 differences are collapsed, and tip labels on affected branches are mapped to internal nodes as directly-sampled ancestral variants. Currently, we process about million genomes in approximately nine hours on 34 cores. The resulting trees are visualized using the JavaScript framework D3.js as ‘beadplots’, in which variants are represented by horizontal line segments, annotated with beads representing samples by collection date. Variants are linked by vertical edges to represent branches in the consensus tree. These visualizations are published at https://filogeneti.ca/CoVizu. All source code was released under an MIT license at https://github.com/PoonLab/covizu.
Sex determination genetransformerregulates the male-female difference inDrosophilafat storage via the adipokinetic hormone pathway
Authors: Wat Lianna W. , Chowdhury Zahid S. , Millington Jason W. , Biswas Puja , Rideout Elizabeth J. 
Published: July 2021

ABSTRACTSex differences in whole-body fat storage exist in many species. For example,Drosophilafemales store more fat than males. Yet, the mechanisms underlying this sex difference in fat storage remain incompletely understood. Here, we identify a key role for sex determination genetransformer(tra) in regulating the male-female difference in fat storage. Normally, a functional Tra protein is present only in females, where it promotes female sexual development. We show that loss of Tra in females reduced whole-body fat storage, whereas gain of Tra in males augmented fat storage. Tra’s role in promoting fat storage was largely due to its function in neurons, specifically the Adipokinetic hormone (Akh)-producing cells (APCs). Our analysis of Akh pathway regulation revealed a male bias in APC activity and Akh pathway function, where this sex-biased regulation influenced the sex difference in fat storage by limiting triglyceride accumulation in males. Importantly, Tra loss in females increased Akh pathway activity, and genetically manipulating the Akh pathway rescued Tra-dependent effects on fat storage. This identifies sex-specific regulation of Akh as one mechanism underlying the male-female difference in whole-body triglyceride levels, and provides important insight into the conserved mechanisms underlying sexual dimorphism in whole-body fat storage.
Measuring cystic fibrosis drug responses in organoids derived from 2D differentiated nasal epithelia
Authors: Amatngalim Gimano D. , Rodenburg Lisa W. , Aalbers Bente L. , Raeven Henriette H. M. , Aarts Ellen M. , Silva Iris A.L. , Nijenhuis Wilco , Vrendenbarg Sacha , Kruisselbrink Evelien , Brunsveld Jesse E. , van Drunen Cornelis M. , Michel Sabine , de Winter-de Groot Karin M. , Heijerman Harry G. , Kapitein Lukas C. , Amaral Magarida D. , van der Ent Cornelis K. , Beekman Jeffrey M. 
Published: July 2021

AbstractCystic Fibrosis (CF) is caused by genetic defects that impair the cystic fibrosis transmembrane conductance regulator (CFTR) channel in airway epithelial cells. These defects may be overcome by specific CFTR modulating drugs, for which the efficacy can be predicted in a personalized manner using 3D nasal-brushing-derived airway organoids in a forskolin-induced swelling assay. Despite of this, previously described application of 3D airway organoids in CFTR function assays have not been fully optimal. In this report we therefore describe an alternative method of culturing nasal brushing-derived airway organoids, which are created from an equally differentiated airway epithelial monolayer of a 2D air-liquid interface culture. In addition, we have defined organoid culture conditions, with the growth factor/cytokine combination neuregulin-1β and interleukine-1β, which enabled consistent detection of CFTR modulator responses in nasal airway organoids cultures from subjects with CF.
The interplay of additivity, dominance, and epistasis in a diploid yeast cross
Authors: Matsui Takeshi , Mullis Martin N. , Roy Kevin , Hale Joseph J. , Schell Rachel , Levy Sasha F. , Ehrenreich Ian M. 
Published: July 2021

AbstractWe used a double barcoding system to generate and phenotype a panel of ~200,000 diploid yeast segregants that can be partitioned into hundreds of interrelated families. This experimental design enabled the detection of thousands of genetic interactions and many loci whose effects vary across families. Traits were largely specified by a small number of hub loci with major additive and dominance effects, and pervasive epistasis. Genetic background commonly influenced both the additive and dominance effects of loci, with multiple modifiers typically involved. The most prominent dominance modifier was the mating locus, which had no effect on its own. Our findings show that the interplay between additivity, dominance, and epistasis underlies a complex genotype-to-phenotype map in diploids.One sentence summaryIn diploids, epistasis frequently modifies both additivity and dominance.
Distinct Colon Mucosa Microbiomes associated with Tubular Adenomas and Serrated Polyps
Authors: Avelar-Barragan Julio , DeDecker Lauren , Lu Zachary , Coppedge Bretton , Karnes William E. , Whiteson Katrine L. 
Published: July 2021

AbstractBackgroundColorectal cancer is the second most deadly and third most common cancer in the world. Its development is heterogenous, with multiple mechanisms of carcinogenesis. Two distinct mechanisms include the adenoma-carcinoma sequence and the serrated pathway. The gut microbiome has been identified as a key player in the adenoma-carcinoma sequence, but its role in serrated carcinogenesis is less clear. In this study, we characterized the gut microbiome of 140 polyp-free and polyp-bearing individuals using colon mucosa and fecal samples to determine if microbiome composition was associated with each of the two key pathways.ResultsWe discovered significant differences between the microbiomes of colon mucosa and fecal samples, with sample type explaining 14% of the variation observed in the microbiome. Multiple mucosal samples were collected from each individual to investigate whether the gut microbiome differed between polyp and healthy intestinal tissue, but no differences were found. Colon mucosa sampling revealed that the microbiomes of individuals with tubular adenomas and serrated polyps were significantly different from each other and polyp-free individuals, explaining 2-10% of the variance in the microbiome. Further analysis revealed differential abundances of 6 microbes and 1,143 microbial genes across tubular adenoma, serrated polyp, and polyp-free cases.ConclusionBy directly sampling the colon mucosa and distinguishing between the different developmental pathways of colorectal cancer, this study helps characterize potential mechanistic targets for serrated carcinogenesis. This research also provides insight into multiple microbiome sampling strategies by assessing each method’s practicality and effect on microbial community composition.
A Wastewater-based Epidemiology tool for COVID-19 Surveillance in Portugal
Authors: Monteiro Sílvia , Rente Daniela , Cunha Mónica V. , Gomes Manuel Carmo , Marques Tiago A. , Lourenço Artur B. , Cardoso Eugénia , Álvaro Pedro , Silva Marco , Coelho Norberta , Vilaça João , Meireles Fátima , Brôco Nuno , Carvalho Marta , Santos Ricardo 
Published: July 2021

AbstractShedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the feces and urine of infected patients and subsequent presence in wastewater has produced interest on the use of this matrix for sentinel surveillance at a community level and as a complementary approach to syndromic surveillance. With this work, we set the foundations for wastewater-based epidemiology (WBE) in Portugal by monitoring the trends of SARS-CoV-2 RNA circulation in the community, on a nationwide perspective during different epidemiological phases of the pandemic. The Charité assays (E_Sarbecco, RdRP, and N_Sarbecco) were applied to monitor, over 32-weeks (April to December 2020), the dynamics of SARS-CoV-2 RNA at the inlet of five wastewater treatment plants (WWTP), which together serve more than two million people in Portugal. Raw wastewater from three COVID-19 reference hospitals was also analyzed during this period. In total, more than 600 samples were tested. Sampling started late April 2020, during lockdown, and, for the first weeks, detection of SARS-CoV-2 RNA was sporadic, with concentrations varying from 103 to 105 genome copies per liter (GC/L). Prevalence of SARS-CoV-2 RNA increased steeply by the end of May into late June, mainly in Lisboa e Vale do Tejo region (LVT), during the reopening phase. After the summer, with the reopening of schools in mid-September and return to partial face-to-face work, a pronounced increase of SARS-CoV-2 RNA in wastewater was detected. In the LVT area, SARS-CoV-2 RNA load agreed with reported trends in hotspots of infection. Synchrony between trends of SARS-CoV-2 RNA in raw wastewater and daily new COVID-19 cases highlights the value of WBE as a surveillance tool for this virus, particularly after the phasing out of the epidemiological curve and when hotspots of disease re-emerge in the population which might be difficult to spot based solely on syndromic surveillance and contact tracing.
The metabolic, virulence and antimicrobial resistance profiles of colonizing Streptococcus pneumoniae shift after pneumococcal vaccine introduction in urban Malawi
Authors: Gori Andrea , Obolski Uri , Swarthout Todd D. , Lourenço José , Weight Caroline M. , Cornick Jen , Kamng’ona Arox , Mwalukomo Thandie S. , Msefula Jacquline , Brown Comfort , Maiden Martin C. , French Neil , Gupta Sunetra , Heyderman Robert S. 
Published: July 2021

AbstractStreptococcus pneumoniae accounts for at least 300,000 deaths from pneumonia, septicaemia and meningitis among children under 5-years-old worldwide. Protein–polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten to undermine this success. Here, we address the hypothesis that following vaccine introduction in high disease and carriage burden settings, adapted pneumococcal genotypes emerge with the potential to facilitate vaccine escape. We show that beyond serotype replacement, there are marked changes in S. pneumoniae carriage population genetics amongst 2804 isolates sampled 4-8 years after the 2011 introduction of PCV-13 in urban Malawi. These changes are characterised by metabolic genotypes with distinct virulence and antimicrobial resistance (AMR) profiles. This included exclusive genes responsible for metabolism and carbohydrate transport, and toxin-antitoxin systems located in an integrative-conjugative region suggestive of horizontal gene transfer. These emergent genotypes were found to have differential growth, haemolytic, or epithelial adhesion/invasion traits that may confer advantage in the nasopharyngeal niche. Together these data show that in the context of PCV13 introduction in a high burden population, there has been a shift in the pneumococcal population dynamics with the emergence of genotypes that have undergone multiple adaptations extending beyond simple serotype replacement, a process that could further undermine vaccine control and promote the spread of AMR.
Unlike Chloroquine, mefloquine inhibits SARS-CoV-2 infection in physiologically relevant cells and does not induce viral variants
Authors: Sacramento Carolina Q. , Fintelman-Rodrigues Natalia , Dias Suelen S. G. , Temerozo Jairo R. , Da Silva Aline de Paula D. , da Silva Carine S. , Ferreira André C. , Mattos Mayara , Soares Vinicius C. , Pereira-Dutra Filipe , Miranda Milene D. , Barreto-Vieira Debora F. , da Silva Marcos Alexandre N. , Santos Suzana S. , Torres Mateo , Rajoli Rajith K R , Paccanaro Alberto , Owen Andrew , Bou-Habib Dumith Chequer , Bozza Patrícia T. , Souza Thiago Moreno L. 
Published: July 2021

AbstractRepositioning of clinical approved drugs could represent the fastest way to identify therapeutic options during public health emergencies, the majority of drugs explored for repurposing as antivirals for 2019 coronavirus disease (COVID-19) have failed to demonstrate clinical benefit. Without specific antivirals, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to cause major global mortality. Antimalarial drugs, such as chloroquine (CQ)/hydroxychloroquine (HCQ) and mefloquine have emerged as potential anti-SARS-CoV-2 antivirals. CQ/HCQ entered the Solidarity and RECOVERY clinical trials against COVID-19 and showed lack of efficacy. Importantly, mefloquine is not a 4-aminoquinoline like CQ and HCQ and has been previously repurposed for other respiratory diseases. Unlike the 4-aminoquinolines that accumulate in the high pH of intracellular lysosomes of the lung, the high respiratory tract penetration of mefloquine is driven by its high lipophilicity. While CQ and HCQ exhibit activity in Vero E6 cells, their activity is obviated in TMPRSS2-expressing cells, such as Calu-3 cells, which more accurately recapitulate in vivo entry mechanisms for SARS-CoV-2. Accordingly, here we report the anti-SARS-CoV-2 activity of mefloquine in Calu-3 type II pneumocytes and primary human monocytes. Mefloquine inhibited SARS-CoV-2 replication in Calu-3 cells with low cytotoxicity and EC50and EC90values of 1.2 and 5.3 µM, respectively. In addition, mefloquine reduced up to 68% the SARS-CoV-2 RNA levels in infected monocytes, reducing viral-induced inflammation. Mefloquine blocked early steps of the SARS-CoV-2 replicative cycle and was less prone than CQ to induce drug-associated viral mutations and synergized with RNA polymerase inhibitor. The pharmacological parameters of mefloquine are consistent with its plasma exposure in humans and its tissue-to-plasma predicted coefficient points that this drug may accumulate in the lungs. These data indicate that mefloquine could represent an orally available clinically approved drug option against COVID-19 and should not be neglected on the basis of the failure of CQ and HCQ.
Ultrastructure expansion microscopy of Plasmodium gametocytes reveals the molecular architecture of a microtubule organisation centre coordinating mitosis with axoneme assembly
Authors: Rashpa Ravish , Brochet Mathieu 
Published: July 2021

AbstractThe transmission of malaria-causing parasites to mosquitoes relies on the production of the gametocyte stages and their development into gametes upon a blood feed. These stages display various microtubule cytoskeletons and the architecture of the corresponding microtubule organisation centres (MTOC) remains elusive. Combining ultrastructure expansion microscopy (U-ExM) with bulk proteome labelling, we first reconstructed in 3D the subpellicular microtubule network and its associated actin cytoskeleton, which confer cell rigidity to Plasmodium falciparum gametocytes. Upon activation, as the microgametocyte undergoes three rounds of endomitosis, it simultaneously assembles axonemes to form eight flagellated microgametes. Here, U-ExM combined with Pan-ExM revealed the molecular architecture of a single bipartite MTOC coordinating mitosis with axoneme formation. This MTOC spans the nuclear membrane linking acentriolar mitotic plaques to cytoplasmic basal bodies by proteinaceous filaments. The eight basal bodies are concomitantly de novo assembled from a deuterosome-like structure, where centrin, γ-tubulin, SAS4/CPAP and SAS6 form distinct subdomains. Once assembled, the basal bodies show a fusion of the proximal and central cores where colocalised centrin and SAS6 are surrounded by a SAS4/CPAP-toroid in the lumen of the microtubule wall. Sequential nucleation of axonemes and mitotic spindles is associated with a dynamic movement of γ-tubulin from the basal bodies to the acentriolar plaques. We finally show that this atypical MTOC architecture relies on two non-canonical MTOC regulators, the calcium-dependent protein kinase 4 and the serine/arginine-protein kinase 1. Altogether, these results provide insights into the molecular organisation of a bipartite MTOC that may reflect a functional transition of a basal body to coordinate axoneme formation with mitosis.