bluuebunny/crossref_metadata_2025_split huggingface dataset:
A core transcriptional response for biofilm formation by Y. pseudotuberculosis
Authors: Mahmud A.K.M.F. , Nilsson K. , Soni D.K. , Choudhury R. , Navais R. , Tuck Simon , Avican K. , Fällman M. 
Published: March 2022

AbstractPrevious transcriptional profiling of the enteropathogen Yersinia pseudotuberculosis during persistent stages of colonisation of mouse cecal lymphoid follicles indicated the possible involvement of biofilm in infection maintenance. Not much is known about the mechanisms responsible for biofilm formation by this pathogen, and most current knowledge is based on results of experiments conducted using the related Y. pestis pathogen that forms biofilm in the flea gut. In this study, we performed transcriptional profiling of Y. pseudotuberculosis in biofilms from different biofilm-inducing conditions, bile exposure, amino acid deprivation and in vivo mimicking conditions with and without oxygen. The comparison of differential expression of genes in biofilm versus planktonic bacteria showed a set of 54 core genes that were similarly regulated, independent of inducing condition. This set included many genes that were previously shown to be associated with biofilms, such as hutG, hsmF, hmsT and cpxP that were upreg-ulated and other genes such as hmsP and rfaH that were downregulated. There were also novel biofilm-associated genes, including genes encoding hypothetical proteins. To identify the genes involved in inducing biofilm formation, the gene expression of bacteria during an early initial phase when biofilm starts to form after induction by bile or amino acid depletion was determined. Comparisons of the resulting gene expression profiles with the profiles of non-induced bacteria incubated for the same period of time showed a set of core genes associated with early biofilm formation. This set included genes involved in quorum sensing, pili biogenesis and genes indicative of a potential metabolic shift involving nitrogen utilisation. Genes encoding components of sugar phosphotransferase systems were also up-regulated during biofilm induction. Assays of biofilm formation by bacteria deleted of some of these core genes showed that strains lacking hpr and luxS, which are known to be important for functional sugar phosphotransferase systems and quorum sensing, as well as glnL encoding a sensory histidine kinase were most negatively affected. Most of the deletion mutant strains tested were affected, but the effect was less severe, suggesting high levels of redundancy in the pathways involved in biofilm formation by this pathogen.
CRISPRcleanRWebApp: an interactive web application for processing genome-wide pooled CRISPR-Cas9 viability screens
Authors: Vinceti Alessandro , de Lucia Riccardo Roberto , Cremaschi Paolo , Perron Umberto , Karacok Emre , Mauri Luca , Fernandez Carlos , Kluczynski Krzysztof Henryk , Anderson Daniel Stephen , Iorio Francesco 
Published: March 2022

SummaryA limitation of pooled CRISPR-Cas9 viability screens is the high false-positive rate in detectingessential genesarising from copy number-amplified (CNA) regions of the genome. To solve this issue, we developedCRISPRcleanR: a computational method implemented as R/python package and in a dockerized version. CRISPRcleanR detects and corrects biased responses to CRISPR-Cas9 targeting in an unsupervised fashion, accurately reducing false-positive signals, while maintaining sensitivity in identifying relevant genetic dependencies. Here, we presentCRISPRcleanRWebApp, a web-based application enabling access to CRISPRcleanR through an intuitive graphical web-interface. CRISPRcleanRWebAppremoves the complexity of low-level R/python-language user interactions; it provides a user-friendly access to a complete analytical pipeline, not requiring any data pre-processing, and generating gene-level summaries of essentiality with associated statistical scores; it offers a range of interactively explorable plots, while supporting a wider range of CRISPR guide RNAs’ libraries with respect to the original package. CRISPRcleanRWebAppis freely available at:https://crisprcleanr-webapp.fht.org/.HighlightsCRISPR-Cas9 screens are widely used for the identification of cancer dependenciesIn such screens, false-positives arise from targeting copy number amplified genesCRISPRcleanR corrects this bias in an unsupervised fashionCRISPRcleanRWebAppis a web user-friendly front-end for CRISPRcleanRAbstract Figure
Development of a tractable model system to mimic wood-ageing of beer on a lab scale
Authors: Bossaert Sofie , Kocijan Tin , Winne Valérie , Van Opstaele Filip , Schlich Johanna , Herrera-Malaver Beatriz , Verstrepen Kevin J. , De Rouck Gert , Lievens Bart , Crauwels Sam 
Published: March 2022

AbstractWood-ageing of conventionally fermented beers is gaining increased attention in the production of sour beers with a noteworthy balance between sourness, wood aroma and flavour complexity. Besides the extraction of wood-derived compounds into the beer, wood-aged sours owe their layered flavour profile to the activity of a variety of ‘wild’ microorganisms that reside in the barrels or that emerge from the brewing or maturation environment. However, until now wood-ageing of craft beers largely remains a process of trial and error that often generates unexpected or undesirable results. Therefore, to better understand the process and develop control strategies to improve the consistency, predictability and overall quality of the resulting beer, more insight is needed into the interactions between the wood, the microorganisms and the maturing beer. Nevertheless, as studying these interactions on an industrial scale is highly challenging, the objective of this study was to develop a reproducible and easy-to-manipulate experimentally tractable system that can be used to study wood-ageing of beer on a lab scale. Barrel-ageing was mimicked in a 0.5 liter glass jar filled with beer and closed off by a wooden disk. Furthermore, the system was equipped with a synthetic community composed of four bacterial species (Acetobacter malorum, Gluconobacter oxydans, Lactobacillus brevisandPediococcus damnosus) and four fungal species (Brettanomyces bruxellensis, Candida friedrichii, Pichia membranifaciensandSaccharomyces cerevisiae) that represented key microbes previously identified in wood-ageing experiments with 225-liter barrels. In order to test the hypothesis that the barrel-ageing process of beer can be replicated in the simplifiedin-vitrosystem, the system was subjected to 60 days of ageing and microbial community dynamics and beer chemistry were compared with a 38-week industrial barrel-ageing experiment using the same beer. Beer samples were collected at regular time points and subjected to both qPCR assays targeting the eight selected species and chemical analysis. Results revealed thatin vitroageing showed similar trends in the temporal dynamics of the microbial populations and beer chemistry as those observed during 38-weeks of barrel-ageing in 225-liter barrels. Furthermore, results were found to be highly reproducible. Altogether, thein-vitrosystem was found to be a robust and reproducible system that has great potential to perform more in-depth research about the intricate interactions between microbes, wood and maturing beer and to develop control strategies to improve the consistency, predictability and overall quality of the resulting beer.
Increased receptor affinity and reduced recognition by specific antibodies contribute to immune escape of SARS-CoV-2 variant Omicron
Authors: Vogt Anne-Cathrine , Augusto Gilles , Martina Byron , Chang Xinyue , Nasrallah Gheyath , Speiser Daniel E. , Vogel Monique , Bachmann Martin F. , Mohsen Mona O. 
Published: March 2022

AbstractIn this report, we mechanistically reveal how the Variant of Concern (VOC) SARS-CoV-2 Omicron (B.1.1.529) escapes neutralizing antibody responses, by characterization of this variant, and wildtype Wuhan and Delta variant (B.1.617.2). Convalescent sera as well as sera obtained from participants who received two or three doses of mRNA vaccines (Moderna-mRNA-1273® or Pfizer-BNT162b2®) were used for comparison in this study. Our data demonstrate that both the Delta as well as Omicron variants exhibit higher affinity for the receptor ACE2, facilitating infection and causing antibody escape by receptor affinity (affinity escape), due to reduced ability of antibodies to compete with RBD-receptor interaction and virus neutralization. In contrast, only Omicron but not Delta variant escaped antibody recognition, most likely because only Omicron exhibit the mutation at position E484 associated with reduced recognition, resulting in further reduced neutralization (specificity escape). Nevertheless, the immunizations with RNA based vaccines resulted in marked viral neutralization in vitro for all strains, compatible with the fact that Omicron is still largely susceptible to vaccination-induced antibodies, despite affinity- and specificity escape.
Hypoxia shapes the immune landscape in lung injury promoting inflammation persistence
Authors: Mirchandani Ananda S. , Jenkins Stephen J. , Bain Calum C. , Lawson Hannah , Coelho Patricia , Murphy Fiona , Griffith David , Zhang Ailiang , Sanchez-Garcia Manuel A. , Reyes Leila , Morrison Tyler , Arienti Simone , Sadiku Pranvera , Watts Emily R. , Dickinson Rebecca. S. , Clark Sarah , Ly Tony , Lewis David , Kelly Van , Spanos Christos , Musgrave Kathryn M. , Delaney Liam , Harper Isla , Scott Jonathan , Parkinson Nicholas J. , Rostron Anthony J. , Baillie Kenneth J , Clohisey Sara , Pridans Clare , Campana Lara , Starkey-Lewis Philip , Simpson A John , Dockrell David , Schwarze Jurgen , Hirani Nikhil , Ratcliffe Peter J. , Pugh Christopher W. , Kranc Kamil , Forbes Stuart J. , Whyte Moira K. , Walmsley Sarah R. 
Published: March 2022

AbstractAcute Respiratory Distress Syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, has no cure. Hypoxemia is a defining feature, yet its impact on inflammation is often neglected. Patients with ARDS are monocytopenic early in the onset of the disease. Endotoxin or Streptococcus pneumoniae acute lung injury (ALI) in the context of hypoxia replicates this finding, through hypoxia-driven suppression of type I interferon signalling. This results in failed lung monocyte-derived interstitial macrophages (IM) niche expansion and unchecked neutrophilic inflammation. Administration of colony stimulating factor 1 (CSF1) rescues the monocytopenia, alters the circulating classical monocyte phenotype in hypoxic endotoxin-driven ALI and enables lung IM population expansion, thus limiting lung injury in endotoxin- and virally-induced hypoxic ALI. Hypoxia directly alters immune dynamics to the detriment of the host and manipulation of this aberrant response offers new therapeutic strategies for ARDS.
Kaposi’s sarcoma-associated herpesvirus induces specialised ribosomes to efficiently translate viral lytic mRNAs
Authors: Murphy James C. , Schumann Sophie , Harrington Elena , Vasconcelos Elton J. R. , Mottram Timothy J. , Aspden Julie L. , Whitehouse Adrian 
Published: March 2022

AbstractHistorically, ribosomes have been viewed as unchanged homogeneous macromolecular machines with no intrinsic regulatory capacity for mRNA translation. However, an emerging concept is that heterogeneity of ribosomal composition exists, which can exert a regulatory function or specificity in translational control. This is supported by recent discoveries identifying compositionally distinct ‘specialised ribosomes’ that actively regulate mRNA translation. Viruses lack their own translational machinery and impose a high translational demand on the host cell during replication. Here we explore the possibility that Kaposi’s sarcoma-associated herpesvirus (KSHV) can manipulate host ribosome biogenesis during infection to produce specialised ribosomes which preferentially translate viral transcripts. Quantitative proteomic analysis has identified changes in the stoichiometry and composition of precursor ribosomal complexes during the switch from latent to lytic KSHV replication. Intriguingly, we demonstrate the enhanced association of ribosomal biogenesis factors BUD23 and NOC4L, and a previously uncharacterised KSHV lytic protein, ORF11, with small ribosomal subunit precursor complexes during lytic KSHV infection. Notably, BUD23 depletion resulted in significantly reduced viral gene expression and progression through the lytic cascade, culminating in a dramatic reduction of infectious virion production. Importantly, ribosome profiling demonstrated that BUD23 is essential for the reduced association of ribosomes with KSHV uORFs in late lytic genes, required for the efficient translation of the main open reading frame. Together our results provide new mechanistic insights into KSHV-mediated manipulation of cellular ribosome composition inducing a population of specialised ribosomes to facilitate efficient translation of viral mRNAs.
The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor
Authors: Agrawal Ritvija , Gillies John P. , Zang Juliana L. , Zhang Jingjing , Garrott Sharon R. , Shibuya Hiroki , Nandakumar Jayakrishnan , DeSantis Morgan E. 
Published: March 2022

ABSTRACTDynein harnesses ATP hydrolysis to move cargo on microtubules in multiple biological contexts. Dynein meets a unique challenge in meiosis by moving chromosomes tethered to the nuclear envelope to facilitate homolog pairing essential for gametogenesis. Though processive dynein motility requires binding to an activating adaptor, the identity of the activating adaptor required for dynein to move meiotic chromosomes is unknown. We show that the meiosis-specific nuclear-envelope protein KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved among activating adaptors and converts dynein into a processive motor. We map the dynein-binding surface of KASH5, identifying mutations that abrogate dynein binding in vitro and disrupt recruitment of the dynein machinery to the nuclear envelope in cultured cells and mouse spermatocytes in vivo. Our study identifies KASH5 as the first transmembrane dynein activating adaptor and provides molecular insights into how it activates dynein during meiosis.
Alveolar regeneration following viral infection is independent of tuft cells
Authors: Huang Huachao , Jiang Ming , Zhang Yihan , Biermann Jana , Melms Johannes C. , Danielsson Jennifer A. , Fang Yinshan , Yang Ying , Qiang Li , Liu Jia , Zhou Yiwu , Wang Manli , Hu Zhihong , Wang Timothy C. , Saqi Anjali , Sun Jie , Matsumoto Ichiro , Cardoso Wellington , Emala Charles W. , Zhu Jian , Izar Benjamin , Mou Hongmei , Que Jianwen 
Published: March 2022

AbstractSevere injuries following viral infection cause lung epithelial destruction with the presence of ectopic basal progenitor cells (EBCs), although the exact function of EBCs remains controversial. We and others previously showed the presence of ectopic tuft cells in the disrupted alveolar region following severe influenza infection. Here, we further revealed that the ectopic tuft cells are derived from EBCs. This process is amplified by Wnt signaling inhibition but suppressed by Notch inhibition. Further analysis revealed that p63-CreER labeled population de novo arising during regeneration includes alveolar epithelial cells when Tamoxifen was administrated after viral infection. The generation of the p63-CreER labeled alveolar cells is independent of tuft cells, demonstrating segregated differentiation paths of EBCs in lung repair. EBCs and ectopic tuft cells can also be found in the lung parenchyma post SARS-CoV-2 infection, suggesting a similar response to severe injuries in humans.
PplT domain proteins – ubiquitous potential prokaryotic phospholipid translocases
Authors: Hauser Janna N. , Kengmo Tchoupa Arnaud , Zabel Susanne , Nieselt Kay , Ernst Christoph M. , Slavetinsky Christoph J. , Peschel Andreas 
Published: March 2022

AbstractFlippase proteins exchanging phospholipids between the cytoplasmic membrane leaflets have been identified in Eukaryotes but remained largely unknown in Prokaryotes. Only MprF proteins that synthesize aminoacyl phospholipids in some bacteria have been found to contain a domain that translocates the produced lipids. We show here that this domain, which we named ‘prokaryotic phospholipid translocator’ (PplT), is widespread in Bacteria and Archaea, encoded as a separate protein or fused to different types of enzymes. We also demonstrate that theEscherichia coliPplT protein interacts with many phospholipid-synthetic enzymes and deletion ofpplTimpaired bacterial growth, which supports its potential role in membrane lipid metabolism. PplT domain proteins may be general prokaryotic lipid flippases with critical roles in cellular homeostasis.
IFN-induced protein with tetratricopeptide repeats 2 (Ifit2) limits autoimmune inflammation by regulating myeloid cell activation and metabolic activity
Authors: Kim Dongkyun , Rai Nagendra Kumar , Burrows Amy , Kim Sohee , Tripathi Ajai , Weinberg Samuel E. , Dutta Ranjan , Sen Ganes C. , Min Booki 
Published: March 2022

AbstractBesides anti-viral functions, Type I IFN expresses potent anti-inflammatory properties and is being widely used to treat certain autoimmune conditions, such as multiple sclerosis (MS). In murine model of MS, experimental autoimmune encephalomyelitis (EAE), administration of IFNβ effectively attenuates the disease development. However, the precise mechanisms underlying the treatment remain elusive. In this study, we report that IFN-induced protein with tetratricopeptide repeats 2 (Ifit2), a type I and type III IFN-stimulated gene, plays a previously unrecognized immune regulatory role during autoimmune neuroinflammation. Mice deficient in Ifit2 display greater susceptibility to EAE and escalated immune cell infiltration in the central nervous system. Ifit2 deficiency is also associated with microglial activation and increased myeloid cell infiltration. Unexpectedly, myelin debris clearance and the subsequent remyelination is impaired in Ifit2-/- CNS tissues. Clearing myelin debris is an important property of reparative M2 type myeloid cells to promote remyelination. Indeed, we observed that bone marrow derived macrophages, CNS infiltrating myeloid cells, and microglia from Ifit2-/- mice express cytokine and metabolic genes associated with proinflammatory M1 type subsets. Taken together, our findings uncover a novel regulatory function of Ifit2 in autoimmune inflammation in part by modulating myeloid cell function and metabolic activity.
The role ofUBE3Ain the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons
Authors: Elamin Marwa , Dumarchey Aurelie , Stoddard Christopher , Robinson Tiwanna M. , Cowie Christopher , Gorka Dea , Chamberlain Stormy J. , Levine Eric S. 
Published: March 2022

AbstractChromosome 15q11-q13 duplication syndrome (Dup15q) is a neurodevelopmental disorder caused by maternal duplications of this region. Autism and epilepsy are key features of Dup15q, but affected individuals also exhibit intellectual disability and developmental delay.UBE3A, the gene encoding the ubiquitin protein ligase E3A, is likely a major driver of Dup15q because individuals with maternal, but not paternal 15q duplications have the disorder, andUBE3Ais the only imprinted gene expressed solely from the maternal allele in mature neurons. Nevertheless, the exact role ofUBE3Ais yet to be determined. To establish whetherUBE3Aoverexpression is required for Dup15q neuronal deficits,UBE3Aexpression was manipulated in patient-derived induced pluripotent stem cell (iPSC) lines using antisense oligonucleotides. Dup15q neurons exhibited hyperexcitability features compared to genome-edited isogenic control neurons, and this phenotype was generally prevented by normalizingUBE3Alevels throughoutin vitrodevelopment. Overexpression ofUBE3Ain an iPSC line with a paternal duplication resulted in a profile similar to that of Dup15q neurons except for synaptic phenotypes. These results indicate thatUBE3Aoverexpression is necessary for most Dup15q cellular phenotypes. However, the inability ofUBE3Aoverexpression to recapitulate synaptic phenotypes suggests an important role for non-imprinted genes in the disorder.
Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions
Authors: Markicevic Marija , Sturman Oliver , Bohacek Johannes , Rudin Markus , Zerbi Valerio , Fulcher Ben D. , Wenderoth Nicole 
Published: March 2022

AbstractUnderstanding how the brain’s macroscale dynamics are shaped by underlying microscale mechanisms is a key problem in neuroscience. In animal models, we can now investigate this relationship in unprecedented detail by directly manipulating cellular-level properties while measuring the whole-brain response using resting-state fMRI. Here we focused on understanding how blood-oxygen-level-dependent (BOLD) dynamics, measured within a structurally well-defined striato-thalamo-cortical circuit, are shaped by chemogenetically exciting or inhibiting D1 medium spiny neurons (MSNs) of the right dorsomedial striatum (CPdm). We characterize changes in both the BOLD dynamics of individual cortical and subcortical brain areas, and patterns of inter-regional coupling (functional connectivity) between pairs of areas. Using a classification approach based on a large and diverse set of time-series properties, we found that CPdm neuromodulation alters BOLD dynamics within thalamic subregions that project back to dorsomedial striatum. In the cortex, the strongest changes in local dynamics were observed in unimodal regions, i.e., regions that process information from a single sensory modality, while changes in the local dynamics weakened along a putative cortical hierarchical gradient towards transmodal regions. In contrast, a decrease in functional connectivity was observed only for cortico-striatal connections after D1 excitation. Our results provide a comprehensive understanding of how targeted cellular-level manipulations affect local BOLD dynamics at the macroscale, including the role of a circuit’s structural characteristics and hierarchical cortical level in shaping those dynamics. These findings contribute to ongoing attempts to understand the influence of structure–function relationships in shaping inter-regional communication at subcortical and cortical levels.