bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting C5aR1 signaling reduced neutrophil extracellular traps and ameliorates COVID-19 pathology
Authors: Silva Bruna M. , Veras Flavio P. , Gomes Giovanni F. , Cambier Seppe , Silva Gabriel V. L. , Quadros Andreza U. , Caetité Diego B. , Nascimento Daniele C. , Silva Camilla M. , Silva Juliana C. , Damasceno Samara , Schneider Ayda H. , Beretta Fabio , Batah Sabrina S. , Castro Icaro M. S. , Paiva Isadora M. , Rodrigues Tamara , Salina Ana , Martins Ronaldo , Cebinelli Guilherme C.M. , Bibo Naira L. , Jorge Daniel M. , Nakaya Helder I. , Zamboni Dario S. , Leiria Luiz O. , Fabro Alexandre T. , Alves-Filho José C. , Arruda Eurico , Louzada-Junior Paulo , Oliveira Renê D. , Cunha Larissa D. , Mol Pierre Van , Vanderbeke Lore , Feys Simon , Wauters Els , Brandolini Laura , Cunha Fernando Q. , Köhl Jörg , Allegretti Marcello , Lambrechts Diether , Wauters Joost , Proost Paul , Cunha Thiago M. 
Published: July 2022

AbstractPatients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions, and plays immunopathological roles in inflammatory diseases, we investigated whether C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill COVID-19 patients compared to patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular trap (NET)s-dependent immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonist of C5aR1 could be useful for COVID-19 treatment.
The contrasted impacts of grasshoppers on soil microbial activities in function of primary production and herbivore diet
Authors: Ibanez Sébastien , Foulquier Arnaud , Brun Charles , Colace Marie-Pascale , Piton Gabin , Bernard Lionel , Gallet Christiane , Clément Jean-Christophe 
Published: July 2022

AbstractHerbivory can have contrasted impacts on soil microbes and nutrient cycling, which has stimulated the development of conceptual frameworks exploring the links between below- and aboveground processes. The “productivity model” predicts that herbivores stimulate microbial activities and accelerate nutrient mineralization in productive ecosystems, while they have an opposite effect in less productive ecosystems. In parallel, the “diet model” predicts that herbivores feeding on conservative plants accelerate nutrient cycling while those feeding on exploitative plants decelerate nutrient cycling, due to changes in litter inputs. Since these two frameworks can lead to conflicting predictions in some cases, experimental evidence combining herbivore diet and plant productivity is required.During two consecutive years, we conducted an experiment controlling the presence of three grasshopper species consuming either grasses, forbs or both in twelve natural and managed alpine grasslands with contrasted productivities. In order to assess the effects of herbivory on soil microbes, we measured their extracellular enzymatic activities, biomass and potential nitrogen mineralization (PNM). Soil and vegetation were also characterized to test how much they modulated the effects of herbivory on microbes.Contrary to the predictions of the diet model, the effects of herbivory on microbial characteristics did not depend on the herbivores diet, but were influenced by primary production, though in a way that differed from the productivity model. The most productive sites were constituted by exploitative plant species which depleted N resources in the soil, and by microbes producing relatively few extracellular enzymes, leading to a lower PNM. Herbivory increased microbial biomass and decreased the production of extracellular enzymes in those sites, possibly through the stimulation of root exudates produced by exploitative species. The least productive sites were characterized by conservative plants, high soil C content, and by microbes having a resource acquisition strategy (more extracellular enzymes, higher PNM). Herbivory decreased microbial biomass and increased the production of extracellular enzymes in those sites. This pattern can be explained by the loss of carbon associated with insect respiration, which increases the resource requirements of microbes and by a lower production of root exudates by conservative species. Therefore, the effects of two years of herbivory on soil microbes were at odds with the productivity model, which focuses instead on longer term effects corresponding to herbivory-induced changes in plant species composition. This highlights the multidimensional feature of the impacts of herbivory on ecosystem functioning, both in space and time.
A species-specific lncRNA modulates the reproductive ability of the Asian tiger mosquito
Authors: Belavilas-Trovas Alexandros , Gregoriou Maria-Eleni , Tastsoglou Spyros , Soukia Olga , Giakountis Antonis , Mathiopoulos Kostas 
Published: July 2022

AbstractLong non-coding RNA (lncRNA) research has emerged as an independent scientific field in recent years. Despite their association with critical cellular and metabolic processes in plenty of organisms, lncRNAs are still a largely unexplored area in mosquito research. We propose that they could serve as exceptional tools for pest management due to unique features they possess. These include low inter-species sequence conservation and high tissue specificity. In the present study, we investigated the role of ovary-specific lncRNAs in the reproductive ability of the Asian tiger mosquito,Aedes albopictus. Through the analysis of transcriptomic data, we identified several lncRNAs that were differentially expressed upon blood feeding; we called these genes Norma (NOn-codingRNA inMosquito ovAries). We observed that silencing some of these Normas resulted in significant impact on mosquito fecundity and fertility. We further focused on Norma3 whose silencing resulted in 43% oviposition reduction and 53% hatching reduction of the laid eggs, compared to anti-GFP controls. Moreover, a significant downregulation of a neighboring (∼100 Kb) mucins cluster was observed in smaller anti-Norma3 ovaries, indicating a potential mechanism of in-cisregulation between Norma3 and the mucins. Our work constitutes the first experimental proof-of-evidence connecting lncRNAs with mosquito reproduction and opens a novel path for pest management.
Noninvasive cancer detection by extracting and integrating multi-modal data from whole-methylome sequencing of plasma cell-free DNA
Authors: Bie Fenglong , Wang Zhijie , Li Yulong , Hong Yuanyuan , Han Tiancheng , Lv Fang , Yang Shunli , Li Suxing , Li Xi , Nie Peiyao , Zang Ruochuan , Zhang Moyan , Song Peng , Feng Feiyue , Guo Wei , Duan Jianchun , Bai Guangyu , Li Yuan , Huai Qilin , Zhou Bolun , Huang Yu , Chen Weizhi , Tan Fengwei , Gao Shugeng 
Published: July 2022

AbstractPlasma cell-free DNA (cfDNA) methylation and fragmentation signatures have been shown to be valid biomarkers for blood-based cancer detection. However, conventional methylation sequencing assays are inapplicable for fragmentomic profiling due to bisulfite-induced DNA damage. Here using enzymatic conversion-based low-pass whole-methylome sequencing (WMS), we developed a novel approach to comprehensively interrogate the genome-wide plasma methylation, fragmentation, and copy number profiles for sensitive and noninvasive multi-cancer detection. With plasma WMS data from a clinical cohort comprising 497 healthy controls and 780 patients with both early- and advanced-stage cancers of the breast, colorectum, esophagus, stomach, liver, lung, or pancreas, genomic features including methylation, fragmentation size, copy number alteration, and fragment end motif were extracted individually and subsequently integrated to develop an ensemble cancer classifier, called THEMIS, using machine learning algorithms. THEMIS outperformed individual biomarkers for differentiating cancer patients of all seven types from healthy individuals and achieved a combined area under the curve value of 0.971 in the independent test cohort, translating to a sensitivity of 86% and early-stage (I and II) sensitivity of 77% at 99% specificity. In addition, we built a cancer signal origin classifier with true-positive cancer samples at 100% specificity based on methylation and fragmentation profiling of tissue-specific accessible regulatory elements, which localized cancer-like signal to a limited number of clinically informative sites with 66% accuracy. Overall, this proof-of-concept work demonstrates the feasibility of extracting and integrating multi-modal biomarkers from a single WMS run for noninvasive detection and localization of common cancers across stages.
A comprehensive study of the microbiome and resistome of chicken waste from intensive farms
Authors: Błażejewska Aleksandra , Zalewska Magdalena , Grudniak Anna , Popowska Magdalena 
Published: July 2022

AbstractThe application of chicken waste to farmland could be detrimental to public health. It may contribute to the dissemination of antibiotic resistance genes (ARG) and antibiotic-resistant bacteria (ARB) from feces and their subsequent entry to the food chain. The present study analyzes the metagenome and resistome of chicken manure and litter obtained from a commercial chicken farm in Poland. ARB were isolated, identified and screened for antibiogram fingerprints using standard microbiological and molecular methods. The physicochemical properties of the chicken waste were also determined. ARG, integrons, and mobile genetic elements (MGE) in chicken waste were analyzed by high-throughput SmartChip qPCR. The results confirm the presence of many ARGs, probably located in MGE, which can be transferred to other bacteria. Potentially pathogenic or opportunistic microorganisms and phytopathogens were isolated. More than 50% of the isolated strains were classified as multi-drug resistant, and the remainder were resistant to at least one antibiotic class; these pose a real risk of entering groundwater and contaminating the surrounding environment. Our results indicate that while chicken manure can be sufficient sources of the nutrients essential for plant growth, its microbiological aspects make this material highly dangerous to the environment.
Negative regulation of p53 by the poliovirus receptor PVR is a target of a human cytomegalovirus immune evasion molecule
Authors: Odell Adam F. , Mannion Aarren J. , Jones Pamela F. , Cook Graham P. 
Published: July 2022

AbstractInitially characterised for its role in maintaining genome integrity, p53 has emerged as a critical hub for coordinating cellular responses to diverse types of stress. Here we identify cell surface receptor loss as a signal for p53 induction. The poliovirus receptor (PVR) regulates angiogenesis, leucocyte adhesion and immune surveillance. We demonstrate that loss of PVR from endothelial cells also promotes cell cycle arrest through the induction of a p53 transcriptional programme. The p53 induction is post-translational and, despite remaining associated with MDM2, p53 exhibits reduced ubiquitination, aiding its stabilisation. Increased expression of PVR marks malignant or infected cells, and retention of PVR in the endoplasmic reticulum by human cytomegalovirus (HCMV) UL141 protein allows HCMV infected cells to evade immunity. We show that intracellular retention of PVR by UL141 prevents p53 induction, allowing HCMV to escape both the immune- and p53-mediated surveillance functions of PVR. These data reveal that p53 coordinates responses to changes in cell surface composition and that the cell intrinsic PVR-p53 pathway coupled with PVR-mediated immune surveillance functions provide a sensor mechanism to maintain expression of this multi-functional cell surface molecule.
Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire
Authors: Rodriguez Oscar L. , Safonova Yana , Silver Catherine A. , Shields Kaitlyn , Gibson William S. , Kos Justin T. , Tieri David , Ke Hanzhong , Jackson Katherine J. L. , Boyd Scott D. , Smith Melissa L. , Marasco Wayne A. , Watson Corey T. 
Published: July 2022

AbstractVariation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) significantly impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes individuals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We show that IGH germline variants determine the presence and frequency of antibody genes in the expressed repertoire, including those enriched in functional elements linked to V(D)J recombination, and overlapping disease-associated variants. These results illuminate the power of leveraging IGH genetics to better understand the regulation, function and dynamics of the antibody response in disease.
Studies on the interaction of three lytic bacteriophages with a wide collection of Escherichia coli strains implicated in swine enteric colibacillosis
Authors: Ferreira Alice , Almeida Carina , Silva Daniela , García-Meniño Isidro , Mora Azucena , Oliveira Hugo , Oliveira Ana 
Published: July 2022

AbstractThe misuse of antibiotics in the swine industry and their on-going restriction requires alternatives to control enterotoxigenic and shiga toxin-producing Escherichia coli (ETEC and STEC, respectively). This study evaluates the potential of three coliphages, vB_EcoM_FJ1, vB_EcoM_FN and vB_EcoM_SP1 against 104 ETEC, STEC and ETEC/STEC strains isolated from pig colibacillosis in Portuguese (2018-2020) and Spanish farms (2006-2016), encompassing 71.2% mcr-positive strains (33.7% with mcr-1, 1.9% mcr-2, 35.6% mcr-4 and 2.9% mcr-5) and 18.3% positive strains for TEM (1%), SHV (6.7%), and CTX-M (11.5%) extended-spectrum beta-lactamase-encoding genes. In general, all bacteriophages presented a narrow lytic spectrum (up to 2.9%) against the 104 ETEC, STEC and ETEC/STEC. Bacteriophages shared >80% overall nucleotide identity with E. coli phage T4 (Tevenvirinae subfamily), but a particular look at the distal part of the long tail fiber (gp38) revealed no homology. All bacteriophages recognize lipopolysaccharides as receptors, and additionally, FN binds to an outer membrane protein A. Bacteriophage-insensitive mutants of vB_EcoM_FJ1 (90%) and vB_EcoM_FN (100%) were shown to be more susceptible to pig serum inactivation comparatively to the parental strain and furthermore, their adhesion capacity to porcine intestinal cells was diminished by, approximately, 90%. Contrariwise, vB_EcoM_SP1 insensitive variants did not display phenotypic differences comparing to the wild-type strain. This study demonstrates that besides being T4-like, these bacteriophages revealed a narrow lytic spectrum against diarrhoeagenic E. coli strains and that the acquisition of novel bacteriophage-encoded adhesins (gp38) seems to be determinant for such results.
Kelpwatch: A new visualization and analysis tool to explore kelp canopy dynamics reveals variable response to and recovery from marine heatwaves
Authors: Bell Tom W. , Cavanaugh Kyle C. , Saccomanno Vienna R. , Cavanaugh Katherine C. , Houskeeper Henry F. , Eddy Norah , Schuetzenmeister Falk , Rindlaub Nathaniel , Gleason Mary 
Published: July 2022

AbstractGiant kelp and bull kelp forests are increasingly at risk from marine heatwave events, herbivore outbreaks, and the loss or alterations in the behavior of key herbivore predators. The dynamic floating canopy of these kelps is well-suited to study via satellite imagery, which provides high temporal and spatial resolution data of floating kelp canopy across the western United States and Mexico. However, the size and complexity of the satellite image dataset has made ecological analysis difficult for scientists and managers. To increase accessibility of this rich dataset, we created Kelpwatch, a web-based visualization and analysis tool. This tool allows researchers and managers to quantify kelp forest change in response to disturbances, assess historical trends, and allow for effective and actionable kelp forest management. Here, we demonstrate how Kelpwatch can be used to analyze long-term trends in kelp canopy across regions, quantify spatial variability in the response to and recovery from the 2014 to 2016 marine heatwave events, and provide a local analysis of kelp canopy status around the Monterey Peninsula, California. We found that 18.6% of regional sites displayed a significant trend in kelp canopy area over the past 38 years and that there was a latitudinal response to heatwave events for each kelp species. The recovery from heatwave events was more variable across space, with some local areas like Bahía Tortugas in Baja California Sur showing high recovery while kelp canopies around the Monterey Peninsula continued a slow decline and patchy recovery compared to the rest of the Central California region. Kelpwatch provides near real time spatial data and analysis support and makes complex earth observation data actionable for scientists and managers, which can help identify areas for research, monitoring, and management efforts.
Adapting to visuomotor rotations in stepped increments increases implicit motor learning
Authors: Modchalingam Shanaathanan , Ciccone Marco , D’Amario Sebastian , ’t Hart Bernard Marius , Henriques Denise Y.P. 
Published: July 2022

ABSTRACTHuman motor adaptation relies on both explicit conscious strategies and implicit unconscious updating of internal models to correct motor errors. Implicit adaptation is powerful, requiring less preparation time before executing adapted movements, but recent work suggests it is limited to some absolute magnitude regardless of the size of a visuomotor perturbation when the perturbation is introduced abruptly. It is commonly assumed that gradually introducing a perturbation should lead to improved implicit learning beyond this limit, but outcomes are conflicting. We tested whether introducing a perturbation in two distinct gradual methods can overcome the apparent limit and explain past conflicting findings. We found that gradually introducing a perturbation in a stepped manner, where participants were given time to adapt to each partial step before being introduced to a larger partial step, led to ∼80% higher implicit aftereffects of learning, but introducing it in a ramped manner, where participants adapted larger rotations on each subsequent reach, did not. Our results clearly show that gradual introduction of a perturbation can lead to substantially larger implicit adaptation, as well as identify the type of introduction that is necessary to do so.
Genome-wide analysis resolves the radiation of New Zealand’s freshwaterGalaxias vulgariscomplex and reveals a candidate species obscured by mitochondrial capture
Authors: Campbell Ciaran S.M. , Dutoit Ludovic , King Tania M. , Craw Dave , Burridge Christopher P. , Wallis Graham P. , Waters Jonathan M. 
Published: July 2022

AbstractFreshwater fish radiations are often characterized by multiple closely-related species in close proximity, which can lead to introgression and associated discordance of mitochondrial and nuclear characterizations of species diversity. As a case in point, single locus nuclear versus mitochondrial analyses of New Zealand’s stream-residentGalaxias vulgariscomplex have yielded conflicting phylogenies. We generate and analyze a genome-wide data set comprising 52,352 SNPs across 187Galaxiasspecimens to resolve the phylogeny of this recent fish radiation. We conduct phylogenetic, PCA, STRUCTURE, and ABBA-BABA analyses to evaluate the evolutionary relationships of lineages in the context of natural and anthropogenic river drainage alterations. In addition to the 11 previously recognized stream-resident lineages, genome-wide data reveal a twelfth candidate species (G. ‘Pomahaka’), apparently obscured by introgressive mitochondrial capture. We identify additional examples of mito-nuclear discordance and putative mitochondrial capture, likely mediated by geological and anthropogenic modification of drainage boundaries. Our study highlights the need for genome-wide approaches for delimiting freshwater biodiversity. Genetic data also reveal the influence of drainage history on freshwater biodiversity, including the rapid divergence of recently fragmented fish populations, and the conservation genetic risks of anthropogenic translocations events.
Electron-counting MicroED data with the K2 and K3 direct electron detectors
Authors: Clabbers Max T.B. , Martynowycz Michael W. , Hattne Johan , Nannenga Brent L. , Gonen Tamir 
Published: July 2022

AbstractMicrocrystal electron diffraction (MicroED) uses electron cryo-microscopy (cryo-EM) to collect diffraction data from small crystals during continuous rotation of the sample. As a result of advances in hardware as well as methods development, the data quality has continuously improved over the past decade, to the point where even macromolecular structures can be determined ab initio. Detectors suitable for electron diffraction should ideally have fast readout to record data in movie mode, and high sensitivity at low exposure rates to accurately report the intensities. Direct electron detectors are commonly used in cryo-EM imaging for their sensitivity and speed, but despite their availability are generally not used in diffraction. Primary concerns with diffraction experiments are the dynamic range and coincidence loss, which will corrupt the measurement if the flux exceeds the count rate of the detector. Here, we describe instrument setup and low-exposure MicroED data collection in electron-counting mode using K2 and K3 direct electron detectors and show that the integrated intensities can be effectively used to solve structures of two macromolecules between 1.2 Å and 2.8 Å. Even though a beam stop was not used in these studies we did not observe damage to the camera. As these cameras are already available in many cryo-EM facilities, this provides opportunities for users who do not have access to dedicated facilities for MicroED.