bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza A virus circumvents the innate immune response through the sequestration of double-stranded RNA
Authors: Nakano Masahiro , Miyamoto Sho , Ohnishi Chiho , Nogami Chiharu , Hirose Nanami , Fujita-Fujiharu Yoko , Muramoto Yukiko , Noda Takeshi 
Published: May 2024

AbstractDouble-stranded RNA (dsRNA), which induces an innate immune response against viral infections, is rarely detected in influenza A virus (IAV)-infected cells. Nevertheless, we previously reported that the IAV ribonucleoprotein complex (vRNP) generates looped dsRNAs during RNA synthesisin vitro. This finding suggests that IAV possesses a specific mechanism for sequestering dsRNA within infected cells, thereby enabling viral evasion of the innate immune response. Here, we found that dsRNAs were produced in infected cells lacking the expression of viral non-structural protein 1 (NS1) and nuclear export protein (NEP), both encoded by the same RNA segment. Interestingly, NS1 molecules masked the entire looped dsRNA generated by vRNP, implying a potential role for NS1 in segregating viral dsRNA from cytoplasmic dsRNA sensors, including retinoic acid inducible gene-I (RIG-I). Furthermore, dsRNAs were sequestered within the nucleus of infected cells due to the absence of NEP, while their translocation to the cytoplasm occurred only upon NEP expression. Notably, the cytoplasmic translocation of dsRNA triggered the innate immune response in an RIG-I-dependent manner. These findings highlight IAV’s distinctive strategy for circumventing innate immunity by sequestration of dsRNAs.Author summaryIt is widely recognized that double-stranded RNA (dsRNA) produced during viral infection triggers an innate immune response. However, the influenza A virus (IAV) has been thought to rarely produce dsRNA within infected cells. Here, we confirmed the limited dsRNA production in the nucleus of IAV-infected cells and found that the cells lacked expressions of viral non-structural protein 1 (NS1) and nuclear export protein (NEP), both derived from a single RNA segment. High-speed atomic force microscopy demonstrated that NS1 entirely concealed dsRNA produced by the viral ribonucleoprotein complexes, thereby segregating it from cytoplasmic dsRNA sensors that trigger the innate immune response. Interestingly, NEP expression caused cytoplasmic translocation of dsRNA, resulting in the nuclear translocation of interferon regulatory factor 3, which initiates an innate immune response. Collectively, our findings suggest that IAV employs a sophisticated strategy to circumvent the innate immune system, wherein the expressions of NS1 and NEP exert considerable influence.
Neural tracking of the speech envelope predicts binaural unmasking
Authors: Dieudonné Benjamin , Decruy Lien , Vanthornhout Jonas 
Published: May 2024

AbstractBinaural unmasking is the remarkable phenomenon that it is substantially easier to detect a signal in noise, when the interaural parameters of the signal are different from those of the noise – a mechanism that comes in handy in so-called cocktail party scenarios. In this study, we investigated the effect of binaural unmasking on neural tracking of the speech envelope. We measured EEG in 8 participants who listened to speech in noise at a fixed signal-to-noise ratio (−12 dB or −9 dB, depending on the speech material), in two conditions: one where speech and noise had the same interaural phase difference (both speech and noise having an opposite waveform across ears,SπNπ), and one where the interaural phase difference of the speech was different from that of the noise (only the speech having an opposite waveform across ears,SπN0). We measured a clear benefit of binaural unmasking in behavioral speech understanding scores, accompanied with increased neural tracking of the speech envelope. Moreover, analyzing the temporal response functions revealed that binaural unmasking also resulted in decreased peak latencies and increased peak amplitudes. Our results are consistent with previous research using auditory evoked potentials and steady-state responses to quantify binaural unmasking at cortical levels. Moreover, they confirm that neural tracking of speech is modulated by speech understanding, even if the acoustic signal-to-noise ratio is kept constant.Significance StatementBinaural unmasking in an important contributing factor to speech understanding in noisy environments. This is the first time that this benefit in speech understanding is measured objectively with EEG. From a clinical perspective, these results could enable the evalu-ation of binaural speech understanding mechanisms in populations for whom behavioral measures are difficult to obtain, such as young children or people with cognitive impair-ment. Moreover, behavioral research has shown that many pathologies (e.g., asymmetric hearing loss, auditory neuropathy, and age-related deficits) are more sensitive to tests that contain a binaural processing component. Our paradigm could enable the detection of such pathologies with an objective approach using neural tracking of speech.
SARS-CoV-2 sequencing artifacts associated with targeted PCR enrichment and read mapping
Authors: Ellegaard Kirsten Maren , Gunalan Vithiagaran , Sieber Raphael , Baig Sharmin Jamshid , Larsen Nicolai Balle , Bennedbæk Marc , Bybjerg-Grauholm Jonas , Escobar-Herrera Leandro Andrés , Hansen Tobias Nikolaj Gress , Thorsen Theis Hass , Krusager Anders , Aasbjerg Gitte Nygaard , Al-Tamimi Nour Saad , Westergaard Casper , Svarrer Christina Wiid , Rasmussen Morten , Stegger Marc 
Published: May 2024

AbstractProtocols and pipelines for SARS-CoV-2 genome sequencing were rapidly established when the COVID-19 outbreak was declared a pandemic. The most widely used approach for sequencing SARS-CoV-2 includes targeted enrichment by PCR, followed by shotgun sequencing and reference-based genome assembly. As the continued surveillance of SARS-CoV-2 worldwide is transitioning towards a lower level of intensity, it is timely to re-visit the sequencing protocols and pipelines established during the acute phase of the pandemic. In the current study, we have investigated the impact of primer scheme and reference genome choice by sequencing samples with multiple primer schemes (Artic V3, V4.1 and V5.3.2) and re-processing reads with multiple reference genomes. We have also analysed the temporal development in ambiguous base calls during the emergence of the BA.2.86.x variant. We found that the primers used for targeted enrichment can result in recurrent ambiguous base calls, which can accumulate rapidly in response to the emergence of a new variant. We also found examples of consistent base calling errors, associated with PCR artifacts and amplicon drop-out. Similarly, misalignments and partially mapped reads on the reference genome resulted in ambiguous base calls, as well as defining mutations being omitted from the assembly. These findings highlight some key limitations of using targeted enrichment by PCR and reference-based genome assembly for sequencing SARS-CoV-2, and the importance of continuously monitoring and updating primer schemes and bioinformatic pipelines.
Short-Term Evolution and Dispersal Patterns of Fluconazole-Resistance inCandida aurisclade III
Authors: Cancino-Muñoz Irving , Mulet-Bayona Juan Vicente , Salvador-García Carme , Tormo-Palop Nuria , Guna Remedios , Gimeno-Cardona Concepción , González-Candelas Fernando 
Published: May 2024

ABSTRACTThe rapid increase of infections caused by the emerging fungal pathogenCandida aurisis of global concern, and understanding its expansion is a priority. The phylogenetic diversity of the yeast is clustered in five major clades, among which clade III is particularly relevant, as most of its strains exhibit resistance to fluconazole, reducing the therapeutic alternatives and provoking outbreaks that are difficult to control. In this study, we have investigated the phylogenetic structure of clade III by analyzing a global collection of 566 genomes. We have identified three subgroups within clade III, among which two are genetically most closely related. Moreover, we have estimated the evolutionary rate of clade III to be 2.25e-7 s/s/y (2.87 changes per year). We found that one of these subgroups shows intrinsic resistance to fluconazole and is responsible for the majority of cases within this clade globally. We inferred that this subgroup may have originated around December 2010 (95% HPD: April 2010 - June 2011), and since then it has spread across continents, generating multiple large outbreaks, each with a unique pattern of transmission and dissemination. These results highlight the remarkable ability of the pathogen to adapt to its environment and its rapid global spread, underscoring the urgent need to effectively address this epidemiological challenge.IMPORTANCEThe number of cases affected byCandida aurishas increased worryingly worldwide. Among the currently recognized clades, clade III has the highest proportion of fluconazole-resistant cases and is spreading very rapidly, causing large nosocomial outbreaks across the globe. By analyzing complete fungal genomes from around the world, we have confirmed the origin of this clade and unraveled its dispersal patterns in the early 2010s. This finding provides knowledge that may be helpful to the public health authorities for the control of the disease.
New drinking water genome catalog identifies a globally distributed bacterial genus adapted to disinfected drinking water systems
Authors: Sudarshan Ashwin S , Dai Zihan , Gabrielli Marco , Oosthuizen-Vosloo Solize , Konstantinidis Konstantinos T. , Pinto Ameet J 
Published: May 2024

AbstractGenome-resolved insights into the structure and function of the drinking water microbiome can advance the effective management of drinking water quality. To enable this, we constructed and curated thousands of metagenome-assembled and isolate genomes from drinking water distribution systems globally to develop a Drinking Water Genome Catalog (DWGC). The current DWGC disproportionately represents disinfected drinking water systems due to a paucity of metagenomes from non-disinfected systems. Using the DWGC, we identify core genera of the drinking water microbiome including a genus (UBA4765) within the orderRhizobialesthat is frequently detected and highly abundant in disinfected drinking water systems. We demonstrate that this genus has been widely detected but incorrectly classified in previous amplicon sequencing-based investigations of the drinking water microbiome. Further, we show that a single genome variant (genomevar) within this genus is detected in >82% of drinking water systems included in this study. We propose a provisional name for this uncultured bacterium as “Raskinella chlorumaquaticus” and describe the genus as “Raskinella” (pending SeqCode approval). Metabolic annotation and modeling-based predictions indicate that this bacterium is capable of necrotrophic growth, able to metabolize halogenated compounds, proliferates in a biofilm-based environment and shows clear indications of disinfection-mediated selection.SynopsisCreation and analysis of a new curated drinking water genome catalog identifies uncharacterized bacterial species that is widely distributed in disinfected drinking water systems.
Extracellular vesicles from microglial cells activated by abnormal heparan sulfate oligosaccharides from Sanfilippo patients impair neuronal dendritic arborization
Authors: Dias Chloé , Ballout Nissrine , Morla Guillaume , Alileche Katia , Santiago Christophe , Guerrera Chiara Ida , Chaubet Adeline , Ausseil Jerome , Trudel Stephanie 
Published: May 2024

AbstractBackgroundIn mucopolysaccharidosis type III (MPS III), a pediatric neurodegenerative disorder, accumulation of abnormal glycosaminoglycans (GAGs) induces severe neuroinflammation by triggering the microglial pro-inflammatory cytokines production via a TLR4-dependent pathway. But the extent of the microglia contribution to the MPS III neuropathology remains unclear. Extracellular vesicles (EVs) mediate intercellular communication and are known to participate in the pathogenesis of adult neurodegenerative diseases. However, characterization of the molecular profiles of EVs released by MPS III microglia and their effects on neuronal functions have not been described.MethodsHere, we isolated EVs secreted by the microglial cells after treatment with GAGs purified from urines of MPS III patients (MPS III-EVs) to explore the EVs’ proteins and small RNA profiles using LC-MS/MS and RNA sequencing. We next performed a functional assay by immunofluorescence following wild-type (WT) or MPS III-EVs uptake by WT primary cortical neurons and analyzed their extensions metrics after staining of βIII-tubulin and MAP2 by confocal microscopy.ResultsFunctional enrichment analysis for both proteomics and RNA sequencing data from MPS III-EVs revealed a specific content involved in neuroinflammation and neurodevelopment pathways. Treatment of cortical neurons with MPS III-EVs induced a disease-associated phenotype demonstrated by a lower total neurite surface area, an impaired somatodendritic compartment, and a higher number of immature dendritic spines.ConclusionsThis study shows, for the first time, that GAGs from patients with MPS III can induce microglial secretion of EVs that deliver a specific molecular message to recipient naive neurons, while promoting the neuroinflammation, and depriving neurons of neurodevelopmental factors. This work provides a framework for further studies of biomarkers to evaluate efficiency of emerging therapies.Graphical abstract
Avian influenza virus neuraminidase stalk length and haemagglutinin glycosylation patterns reveal molecularly directed reassortment promoting the emergence of highly pathogenic clade 2.3.4.4b A (H5N1) viruses
Authors: Nataraj Ranjana , Chandra Anantika , Kesavardhana Sannula 
Published: May 2024

ABSTRACTThe recently emerged panzootic clade 2.3.4.4b H5N1 influenza viruses show unprecedented extensive spread in wild birds and have been transmitted to several mammals, including humans. The virologic factors that have driven the success of the 2.3.4.4b H5N1 viruses, which has not been achieved by previous H5N1 clades, is unclear. We show that the 2.3.4.4b H5 haemagglutinin (HA) paired exclusively with full length (long stalk) N1 neuraminidase (NA) in birds and mammals, unlike previous clades of H5 viruses, which preferentially paired with N1 proteins with stalk deletions (short stalk). We found that the emergence of a 2.3.4.4b H5 HA with seven glycosylation sites was critical in driving its pairing with long stalk N1. The earlier H5 clades that paired with short stalk N1s showed a pattern of eight or more glycosylation sites. A prior shift in a glycosylation site from position 103 to 171 in the receptor binding domain of H5 HA and the subsequent S173A mutation that removed it triggered the emergence of 2.3.4.4b clade H5N1 viruses. Thus, the evolution of novel variations in the H5 HA and their preference for long stalk N1 pairing led to increased fitness and pathogenicity. These observations led us to establish and validate the hypothesis that the pairing of avian virus HA and NA subtypes is not stochastic but is rather molecularly programmed by HA glycosylation and NA stalk length, modulating fitness and emergence of novel avian influenza viruses.GRAPHICAL ABSTRACT
Predicting Theory of Mind in children from the infant connectome
Authors: Schüler Clara , Berger Philipp , Grosse Wiesmann Charlotte 
Published: May 2024

AbstractOur ability to reason about other people’s mental states, labeled Theory of Mind (ToM), is critical for successful human interaction. Despite its importance for human cognition, early predictors of individual ToM development are lacking. Here, we trained a computational model to identify whole-brain connectivity patterns predictive of joint attention, from resting-state fMRI data of 8-15-month-old infants, and tested whether the identified connectome would also predict ToM capacity later in development. First, the model significantly predicted joint attention scores in an independent infant sample. Crucially, the identified connectome did indeed predict ToM in children aged 2-5 years. The default network and its interaction with the ventral attention network formed dominant connections of the network, suggesting that the interplay of bottom-up attention and higher-order cognition paves the way for mature social cognition. These findings provide an early marker for individual differences in social cognitive development, with high potential for the early diagnosis of social cognitive disorders.
Effects of age on responses of principal cells of the mouse anteroventral cochlear nucleus in quiet and noise
Authors: Postolache Maggie , Connelly Graham Catherine J. , Burke Kali , Lauer Amanda M. , Xu-Friedman Matthew A. 
Published: May 2024

AbstractOlder listeners often report difficulties understanding speech in noisy environments. It is important to identify where in the auditory pathway hearing-in-noise deficits arise to develop appropriate therapies. We tested how encoding of sounds is affected by masking noise at early stages of the auditory pathway by recording responses of principal cells in the anteroventral cochlear nucleus (AVCN) of aging CBA/CaJ and C57BL/6J micein vivo. Previous work indicated that masking noise shifts the dynamic range of single auditory nerve fibers (ANFs), leading to elevated tone thresholds. We hypothesized that such threshold shifts could contribute to increased hearing-in-noise deficits with age if susceptibility to masking increased in AVCN units. We tested this by recording the responses of AVCN principal neurons to tones in the presence and absence of masking noise. Surprisingly, we found that masker-induced threshold shifts decreased with age in primary-like units and did not change in choppers. In addition, spontaneous activity decreased in primary-like and chopper units of old mice, with no change in dynamic range or tuning precision. In C57 mice, which undergo early onset hearing loss, units showed similar changes in threshold and spontaneous rate at younger ages, suggesting they were related to hearing loss and not simply aging. These findings suggest that sound information carried by AVCN principal cells remains largely unchanged with age. Therefore, hearing-in-noise deficits may result from other changes during aging, such as distorted across-channel input from the cochlea and changes in sound coding at later stages of the auditory pathway.Significance StatementMiddle age and older listeners commonly experience hearing deficits in the presence of background noise. Central auditory areas have been implicated in hearing-in-noise deficits, but it is not known where these deficits arise. We performedin vivorecordings in mice of different ages at the first stage of the auditory pathway in the brain, the cochlear nucleus, to examine how encoding of sounds is perturbed by masking noise. We found that the responses of individual neurons remain largely intact with age, including the processing of tones in masking noise, despite previously documented structural and physiological degeneration of their auditory nerve inputs. This suggests that problems hearing in masking noise result from changes at other stages of the auditory pathway.
Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation
Authors: Damaa Michella Khoury , Serizay Jacques , Balagué Rémi , Boudjema Amélie-Rose , Faucourt Marion , Delgehyr Nathalie , Goh Kim Jee , Lu Hao , Tan Ee Kim , James Cameron T. , Faucon Catherine , Mitri Rana , Bracht Diana Carolin , Bingle Colin D. , Dunn Norris Ray , Arnold Sebastian J. , Zaragosi Laure-Emmanuelle , Barbry Pascal , Koszul Romain , Omran Heymut , Gil-Gόmez Gabriel , Escudier Estelle , Legendre Marie , Roy Sudipto , Spassky Nathalie , Meunier Alice 
Published: May 2024

AbstractMulticiliated cells (MCC) ensure proper fluid circulation in various organs in metazoans. Their differentiation is marked by the massive ampliication of cilia-nucleating centrioles and is known to be controlled by various cell cycle components. Tn a companion study, we show that the differentiation of MCC is driven by a genuine cell-cycle variant characterized by sequential and wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients withCCNOmutations exhibit a subtype of Primary Ciliary Dyskinesia (PCD) designated as Reduced Generation of Multiple Motile Cilia (RGMC), yet the role of CCNO during MCC differentiation remains unclear. Here, using mice and human cellular models, single cell transcriptomics and functional studies, we show thatCenais activated during a strategic temporal window at the crossroads between the onset of MCC differentiation, the entry into the MCC cell cycle variant, and the activation of the centriole biogenesis program. We ind that the absence ofCenaleads to a block of MCC progenitor differentiation at the G1/S-like transition, just before the beginning of centriole formation. This leads to a complete lack of centrioles and cilia in mouse brain and human airway MCC. Altogether, our study identifies CCNO as a core regulator of entry into the MCC cell cycle variant and shows that the coupling of centriole biogenesis to an S-like phase, maintained in MCC, is dependent on CCNO.One sentence summaryCyclin O is necessary for multiciliated cells to enter their differentiation cell cycle variant and allows the massive amplification of centrioles, which serve as basal bodies for cilia nucleation.
Phage infection fronts trigger early sporulation and collective defense in bacterial populations
Authors: Măgălie Andreea , Marantos Anastasios , Schwartz Daniel A. , Marchi Jacopo , Lennon Jay T. , Weitz Joshua S. 
Published: May 2024

I.ABSTRACTBacteriophage (phage) infect, lyse, and propagate within bacterial populations. However, physiological changes in bacterial cell state can protect against infection even within genetically susceptible populations. One such example is the generation of endospores byBacillusand its relatives, characterized by a reversible state of reduced metabolic activity that protects cells against stressors including desiccation, energy limitation, antibiotics, and infection by phage. Here we tested how sporulation at the cellular scale impacts phage dynamics at population scales when propagating amongstB. subtilisin spatially structured environments. Initially, we found that plaques resulting from infection and lysis were approximately 3-fold smaller on lawns of sporulating wild-type bacteria vs. non-sporulating bacteria. Notably, plaque size was reduced due to an early termination of expanding phage plaques rather than the reduction of plaque growth speed. Microscopic imaging of the plaques revealed ‘sporulation rings’, i.e., spores enriched around plaque edges relative to phage-free regions. We developed a series of mathematical models of phage, bacteria, spore, and small molecules that recapitulate plaque dynamics and identify a putative mechanism: sporulation rings arise in response to lytic activity. In aggregate, sporulation rings inhibit phage from accessing susceptible cells even when sufficient resources are available for further infection and lysis. Together, our findings identify how dormancy can self-limit phage infections at population scales, opening new avenues to explore the entangled fates of phages and their bacterial hosts in environmental and therapeutic contexts.