bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential regulation of degradation and immune pathways underlies adaptation of the ectosymbiotic nematodeLaxus oneistusto oxic-anoxic interfaces
Authors: Paredes Gabriela F. , Viehboeck Tobias , Markert Stephanie , Mausz Michaela A. , Sato Yui , Liebeke Manuel , König Lena , Bulgheresi Silvia 
Published: November 2021

ABSTRACTEukaryotes may experience oxygen deprivation under both physiological and pathological conditions. Because oxygen shortage leads to a reduction in cellular energy production, all eukaryotes studied so far conserve energy by suppressing their metabolism. However, the molecular physiology of animals that naturally and repeatedly experience anoxia is underexplored. One such animal is the marine nematodeLaxus oneistus. It thrives, invariably coated by its sulfur-oxidizing symbiontCandidatusThiosymbion oneisti, in anoxic sulfidic or hypoxic sand. Here, transcriptomics and proteomics showed that, whether in anoxia or not,L. oneistusmostly expressed genes involved in ubiquitination, energy generation, oxidative stress response, immune response, development, and translation. Importantly, ubiquitination genes were also upregulated when the nematode was subjected to anoxic sulfidic conditions, together with genes involved in autophagy, detoxification and ribosome biogenesis. We hypothesize that these degradation pathways were induced to recycle damaged cellular components (mitochondria) and misfolded proteins into nutrients. Remarkably, whenL. oneistuswas subjected to anoxic sulfidic conditions, lectin and mucin genes were also upregulated, potentially to promote the attachment of its thiotrophic symbiont. Furthermore, the nematode appeared to survive oxygen deprivation by using an alternative electron carrier (rhodoquinone) and acceptor (fumarate), to rewire the electron transfer chain. On the other hand, under hypoxia, genes involved in costly processes (e.g., amino acid biosynthesis, development, feeding, mating) were upregulated, together with the worm’s Toll- like innate immunity pathway and several immune effectors (e.g., Bacterial Permeability Increasing proteins, fungicides).In conclusion, we hypothesize that, in anoxic sulfidic sand,L. oneistusupregulates degradation processes, rewires oxidative phosphorylation and by reinforces its coat of bacterial sulfur-oxidizers. In upper sand layers, instead, it appears to produce broad-range antimicrobials and to exploit oxygen for biosynthesis and development.
Three-dimensional Multicolor Subcellular Imaging by Fast Serial Sectioning Tomography for Centimeter-scale Specimens
Authors: Yu Wentao , Kang Lei , Tsang Victor T. C. , Zhang Yan , Wong Ivy H. M. , Wong Terence T. W. 
Published: November 2021

AbstractRapid multicolor three-dimensional (3D) imaging for centimeter-scale specimens with subcellular resolution remains a challenging but captivating scientific pursuit. Here, we present a fast, automated, cost-effective, and versatile multicolor 3D imaging method with ultraviolet (UV) surface excitation and vibratomy-assisted sectioning, termed translational rapid ultraviolet-excited sectioning tomography (TRUST). TRUST enables exogenous molecular-specific fluorescence and endogenous content-rich autofluorescence imaging simultaneously with the help of a UV light-emitting diode and a color camera. Commonly applied tissue preparation procedures (e.g., staining or clearing) are laborious, time-consuming, and may induce detrimental effects on processed samples. In TRUST, formalin-fixed specimens are stained with real-time double labeling layer by layer along with serial widefield optical illumination with raster scanning and mechanical sectioning to improve the staining speed and reveal rich biological information. All vital organs in mice have been imaged by TRUST to demonstrate its fast, robust, and high-content multicolor 3D imaging ability. Moreover, its potential for developmental biology has also been validated by imaging entire mouse embryos (taking ∼2 days for imaging the embryo at the embryonic day of 15). TRUST offers a way for multicontrast and multicolor whole-organ 3D imaging with high resolution and high speed while relieving researchers from heavy sample preparation workload.
Autonomous treatment of bacterial infections in vivo using antimicrobial micro- and nanomachines
Authors: Arqué Xavier , Torres Marcelo D. T. , Patiño Tania , Boaro Andreia , Sánchez Samuel , de la Fuente-Nunez Cesar 
Published: November 2021

ABSTRACTThe increasing resistance of bacteria to existing antibiotics constitutes a major public health threat globally. Most current antibiotic treatments are hindered by poor delivery to the infection site, leading to undesired off-target effects and drug resistance development and spread. Here, we describe micro- and nanomachines that effectively and autonomously deliver antibiotic payloads to the target area. The active motion and antimicrobial activity of the silica-based robots are driven by catalysis of the enzyme urease and antimicrobial peptides, respectively. These antimicrobial machines show micromolar bactericidal activity in vitro against different Gram-positive and Gram-negative pathogenic bacterial strains and act by rapidly depolarizing their membrane. Finally, they demonstrated autonomous anti-infective efficacy in vivo in a clinically relevant abscess infection mouse model. In summary, our machines combine navigation, catalytic conversion, and bactericidal capacity to deliver antimicrobial payloads to specific infection sites. This technology represents a much-needed tool to direct therapeutics to their target to help combat drug-resistant infections.
An evaluation of resonant scanning as a high-speed imaging technique for two-photon imaging of cortical vasculature
Authors: Zhou Annie , Engelmann Shaun A. , Mihelic Samuel A. , Tomar Alankrit , Hassan Ahmed M. , Dunn Andrew K. 
Published: November 2021

AbstractWe demonstrate a simple, low-cost two-photon microscope design with both galvo-galvo and resonant-galvo scanning capabilities. We quantify and compare the signal-to-noise ratios and imaging speeds of the galvo-galvo and resonant-galvo scanning modes when used for murine neurovascular imaging. The two scanning modes perform as expected under shot-noise limited detection and are found to achieve comparable signal-to-noise ratios. Resonant-galvo scanning is capable of reaching desired signal-to-noise ratios using less acquisition time when higher excitation power can be used. Given equal excitation power and total pixel dwell time between the two methods, galvo-galvo scanning outperforms resonant-galvo scanning in image quality when detection deviates from being shot-noise limited.
Genome assembly of the Australian black tiger shrimp (Penaeus monodon) reveals a fragmented IHHNV EVE sequence
Authors: Huerlimann Roger , Cowley Jeff A , Wade Nicholas M , Wang Yinan , Kasinadhuni Naga , Chan Chon-Kit Kenneth , Jabbari Jafar , Siemering Kirby , Gordon Lavinia , Tinning Matthew , Montenegro Juan D , Maes Gregory E , Sellars Melony J , Coman Greg J , McWilliam Sean , Zenger Kyall R , Khatkar Mehar S , Raadsma Herman W , Donovan Dallas , Krishna Gopala , Jerry Dean R 
Published: November 2021

AbstractShrimp are a valuable aquaculture species globally; however, disease remains a major hindrance to shrimp aquaculture sustainability and growth. Mechanisms mediated by endogenous viral elements (EVEs) have been proposed as a means by which shrimp that encounter a new virus start to accommodate rather than succumb to infection over time. However, evidence on the nature of such EVEs and how they mediate viral accommodation is limited. More extensive genomic data on Penaeid shrimp from different geographical locations should assist in exposing the diversity of EVEs. In this context, reported here is a PacBio Sequel-based draft genome assembly of an Australian black tiger shrimp (Penaeus monodon) inbred for one generation. The 1.89 Gbp draft genome is comprised of 31,922 scaffolds (N50: 496,398 bp) covering 85.9% of the projected genome size. The genome repeat content (61.8% with 30% representing simple sequence repeats) is almost the highest identified for any species. The functional annotation identified 35,517 gene models, of which 25,809 were protein-coding and 17,158 were annotated using interproscan. Scaffold scanning for specific EVEs identified an element comprised of a 9,045 bp stretch of repeated, inverted and jumbled genome fragments of Infectious hypodermal and hematopoietic necrosis virus (IHHNV) bounded by a repeated 591/590 bp host sequence. As only near complete linear ~4 kb IHHNV genomes have been found integrated in the genome of P. monodon previously, its discovery has implications regarding the validity of PCR tests designed to specifically detect such linear EVE types. The existence of joined inverted IHHNV genome fragments also provides a means by which hairpin dsRNAs could be expressed and processed by the shrimp RNA interference (RNAi) machinery.
T cells discriminate between groups C1 and C2 HLA-C
Authors: Sim Malcolm J. W. , Stotz Zachary , Lu Jinghua , Brennan Paul , Long Eric O. , Sun Peter D. 
Published: November 2021

AbstractDimorphic residues at positions 77 and 80 delineate HLA-C allotypes into two groups, C1 and C2, which associate with disease through interactions with C1 and C2-specific natural killer cell receptors. How the C1/C2 dimorphism affects T cell recognition is unknown. Using HLA-C allotypes that differ only by the C1/C2-defining residues, we found that KRAS-G12D neoantigen specific T cell receptors (TCR) discriminated groups C1 and C2 HLA-C, due to effects on peptide presentation and TCR affinity. Structural and functional experiments combined with immunopeptidomics analysis revealed that C1-HLA-C favors smaller amino acids at the peptide C-terminus minus-1 position (pΩ-1), and that larger pΩ-1 residues diminished TCR recognition of C1-HLA-C. After controlling for peptide presentation, TCRs exhibited weaker affinities for C2-HLA-C despite conserved TCR contacts. Thus, the C1/C2 dimorphism impacts peptide presentation and HLA-C restricted T cell responses, with implications in multiple disease contexts including adoptive T cell therapy targeting KRAS-G12D-induced cancers.
An optimized ChIP-Seq framework for profiling of histone modifications in Chromochloris zofingiensis
Authors: Strenkert Daniela , Mingay Matthew , Schmollinger Stefan , Chen Cindy , O’Malley Ronan C. , Merchant Sabeeha S. 
Published: November 2021

ABSTRACTThe eukaryotic green alga Chromochloris zofingiensis is a reference organism for studying carbon partitioning and a promising candidate for the production of biofuel precursors. Recent transcriptome profiling transformed our understanding of its biology and generally algal biology, but epigenetic regulation remains understudied and represents a fundamental gap in our understanding of algal gene expression. Chromatin Immunoprecipitation followed by deep sequencing (ChIP-Seq) is a powerful tool for the discovery of such mechanisms, by identifying genome-wide histone modification patterns and transcription factor-binding sites alike. Here, we established a ChIP-Seq framework for Chr. zofingiensis yielding over 20 million high quality reads per sample. The most critical steps in a ChIP experiment were optimized, including DNA shearing to obtain an average DNA fragment size of 250 bp and assessment of the recommended formaldehyde concentration for optimal DNA-protein crosslinking. We used this ChIP-Seq framework to generate a genome-wide map of the H3K4me3 distribution pattern and to integrate these data with matching RNA-Seq data. In line with observations from other organisms, H3K4me3 marks predominantly transcription start sites of genes. Our H3K4me3 ChIP-Seq data will pave the way for improved genome structural annotation in the emerging reference alga Chr. zofingiensis.
α-Synuclein pre-formed fibrils induce prion-like protein aggregation and neurotoxicity in C. elegans models of Parkinson’s disease
Authors: Chen Merry , Vincent Julie , Ezeanii Alexis , Wakade Saurabh , Yerigenahally Shobha , Mor Danielle E. 
Published: November 2021

AbstractParkinson’s disease (PD) is a debilitating neurodegenerative disorder characterized by progressive motor decline and the aggregation of α-synuclein protein. Growing evidence suggests that α-synuclein aggregates may spread from neurons of the digestive tract to the brain in a prion-like manner. While rodent models have recapitulated gut-to-brain α-synuclein transmission, animal models that are amenable to high-throughput investigations are needed to facilitate the discovery of disease mechanisms. Here we describe the first C. elegans models in which feeding with α-synuclein pre-formed fibrils (PFFs) induced prion-like dopamine neuron degeneration and seeding of aggregation of human α-synuclein expressed in the host. PFF acceleration of α-synuclein aggregation in C. elegans muscle cells was associated with a progressive motor deficit, whereas feeding with α-synuclein monomer produced much milder effects. RNAi-mediated knockdown of the C. elegans syndecan sdn-1, and enzymes involved in heparan sulfate proteoglycan biosynthesis, afforded protection from PFF-induced seeding of aggregation and toxicity, as well as dopaminergic neurodegeneration. This work offers new models by which to investigate gut-derived α-synuclein spreading and propagation of disease.
Nanopore adaptive sampling for mitogenome sequencing and bloodmeal identification in hematophagous insects
Authors: Kipp Evan J. , Lindsey Laramie L. , Blanco Cristina M. , Baker Julia , Milstein Marissa S. , Faulk Christopher , Oliver Jonathan D. , Larsen Peter A. 
Published: November 2021

AbstractBlood-feeding insects are important vectors for an array of zoonotic pathogens. Despite significant research focused on well-documented insect vectors of One Health importance, resources for molecular species identification of a large number of hematophagous arthropods are limited. Advancements in next-generation sequencing technologies provide opportunities for targeting mitochondrial genomes of blood-feeding insects, as well as their bloodmeal hosts. This dual approach holds great promise for elucidating complex disease transmission pathways and enhancing the molecular resources for the identification of cryptic insect species. To this end, we leveraged the newly developed Oxford Nanopore Adaptive Sampling (NAS) pipeline to dually sequence the mitogenomes of hematophagous insects and their bloodmeals. Using NAS, we sequenced the entire mitogenomes of Aedes vexans, Culex restuans, Culex territans, and Chrysops niger and successfully identified bloodmeal hosts of Chrysops niger, Culex restuans, and Aedes trivittatus. We show that NAS has the utility to simultaneously molecularly identify blood-feeding insects and characterize disease transmission pathways through bloodmeal host identification. Moreover, our data indicate NAS can facilitate a wide array of molecular systematic studies through novel ‘phylogenetic capture’ methods. We conclude the NAS approach has great potential for informing global One Health initiatives centered on the mitigation of vector-borne disease through dual vector and bloodmeal identification.
Data-Poor Ecological Risk Assessment of Multiple Stressors
Authors: Grewelle Richard E , Mansfield Elizabeth , Micheli Fiorenza , De Leo Giulio 
Published: November 2021

AbstractEcological Risk Assessment is a formal process widely applied to terrestrial, marine, and freshwater ecosystems to evaluate the likelihood of adverse ecological effects occurring as a result of exposure to natural or anthropogenic stressors. For many species, data is sparse and semi-quantitative methodologies provide valuable insight for ecosystem management. Recent statistical developments have improved the quality of these analyses yet a rigorous theoretical framework to assess the cumulative impact of multiple stressors is lacking.We present EcoRAMS, a web application and open-source software module that provides easy-to-use, statistically-robust ecological risk assessments of multiple stressors in data-poor contexts. The software receives attribute scores for two variables (e.g. exposure-sensitivity, productivity-susceptibility, severity-likelihood) via CSV templates and outputs results according to a probabilistic metric of risk.We demonstrate comparative results across a range of assumptions, using simulated and empirical datasets including up to five stressors. Accounting for multiple stressors even when data is limited provides a more detailed analysis of risk that may otherwise be understated in single stressor analyses.This application will allow quantification of risk across data-poor contexts for which statistical results have been previously unavailable. The web app format of EcoRAMS.net lowers the barrier of use for practitioners and scientists at any level of statistical training.
Malaria molecular surveillance in the Peruvian Amazon with a novel highly multiplexedPlasmodium falciparumAmpliseq assay
Authors: Kattenberg Johanna Helena , Fernandez-Miñope Carlos , van Dijk Norbert J. , Llacsahuanga Allcca Lidia , Guetens Pieter , Valdivia Hugo O. , Van geertruyden Jean-Pierre , Rovira-Vallbona Eduard , Monsieurs Pieter , Delgado-Ratto Christopher , Gamboa Dionicia , Rosanas-Urgell Anna 
Published: November 2021

AbstractMolecular surveillance for malaria has great potential to support national malaria control programs (NMCPs). To bridge the gap between research and implementation, several applications (use cases) have been identified to align research, technology development, and public health efforts. For implementation at NMCPs, there is an urgent need for feasible and cost-effective tools.We designed a new highly-multiplexed deep sequencing assay (Pf AmpliSeq), compatible with benchtop sequencers, allowing for high accuracy sequencing at higher coverage and lower cost than WGS, targeting genomic regions of interest. The novelty of the assay is in its high number of targets multiplexed in one easy workflow, combining population genetic markers with 13 near full-length resistance genes, applicable for many different use cases. We provide a first proof-of-principle forhrp2andhrp3deletion detection using amplicon sequencing. Initial sequence data processing can be performed automatically, and subsequent variant analysis requires minimal bioinformatic skills using any tabulated data analysis program.The assay was validated with a retrospective sample collection (n = 254) from the Peruvian Amazon between 2003 and 2018. By combining phenotypic markers and a within-country 28-SNP-barcode, we were able to distinguish different lineages with multiple resistant (dhfr/dhps/crt/mdr1) haplotypes andhrp2andhrp3deletions, increasing in recent years. We found no evidence suggesting the emergence of ART-resistance in Peru. These findings indicate a parasite population under drug pressure, but susceptible to current antimalarials, and demonstrates the added value of a highly multiplexed molecular tool to inform malaria strategies and surveillance systems.ImportanceWhile the power of next generation sequencing technologies to inform and guide malaria control programs has become broadly recognized, integration of genomic data for operational incorporation into malaria surveillance remains a challenge in most malaria endemic countries.The main obstacles include limited infrastructure and accessibility to high-throughput sequencing facilities and the need for local capacity to run in-country analysis of genomes at a large enough scale to be informative for surveillance. In addition, there is a lack of standardized laboratory protocols and automated analysis pipelines to generate reproducible and timely results useful for relevant stakeholders.With our standardized laboratory and bioinformatic workflow, malaria genetic surveillance data can be readily generated by surveillance researchers and malaria control programs in endemic countries, increasing ownership and ensuring timely results for informed decision and policy-making.
Protection offered by mRNA-1273 versus BNT162b2 vaccines against SARS-CoV-2 infection and severe COVID-19 in Qatar
Authors: Abu-Raddad Laith J. , Chemaitelly Hiam , Ayoub Houssein H. , Tang Patrick , Hasan Mohammad R. , Coyle Peter , Yassine Hadi M. , Benslimane Fatiha M. , Al-Khatib Hebah A. , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed Ghaith , Butt Adeel A. , Al-Romaihi Hamad Eid , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto 
Published: November 2021

AbstractBACKGROUNDGrowing evidence suggests that COVID-19 vaccines differ in effectiveness against breakthrough infection or severe COVID-19, but vaccines have yet to be investigated in controlled studies that head-to-head compare immunity of one to another. This study compared protection offered by the mRNA-1273 (Moderna) vaccine with that of the BNT162b2 (Pfizer-BioNTech) vaccine in Qatar.METHODSIn a population of 1,531,736 vaccinated persons, two matched retrospective cohort studies were designed and used to investigate differences in mRNA-1273 and BNT162b2 vaccine protection, after the first and second doses, from December 21, 2020 to October 20, 2021.RESULTSAfter dose 1, cumulative incidence of breakthrough infection was 0.79% (95% CI: 0.75-0.83%) for mRNA-1273-vaccinated individuals and 0.86% (95% CI: 0.82-0.90%) for BNT162b2-vaccinated individuals, 21 days post-injection. Adjusted hazard ratio (AHR) for breakthrough infection was 0.89 (95% CI: 0.83-0.95; p=0.001). AHR was constant in the first two weeks at 1, but it declined to 0.67 (95% CI: 0.57-0.77; p<0.001) in the third week after dose 1. AHR for any severe, critical, or fatal COVID-19 was 0.71 (95% CI: 0.53-0.95; p=0.020). After dose 2, cumulative incidence was 0.59% (95% CI: 0.55-0.64%) for mRNA-1273-vaccinated individuals and 0.84% (95% CI: 0.79-0.89%) for BNT162b2-vaccinated individuals, 180 days post-injection. AHR for breakthrough infection was 0.69 (95% CI: 0.63-0.75; p<0.001) and was largely constant over time after dose 2. AHR for any severe, critical, or fatal COVID-19 was 0.37 (95% CI: 0.10-1.41; p=0.147).CONCLUSIONSmRNA-1273 vaccination is associated with lower SARS-CoV-2 breakthrough infection and COVID-19 hospitalization and death than BNT162b2 vaccination, but the number of hospitalizations and deaths was exceedingly small for both vaccines. Both vaccines demonstrated strikingly similar patterns of build-up of protection after the first dose and waning of protection after the second dose.
Genomic landscape of drug response reveals novel mediators of anthelmintic resistance
Authors: Doyle Stephen R. , Laing Roz , Bartley David , Morrison Alison , Holroyd Nancy , Maitland Kirsty , Antonopoulos Alistair , Chaudhry Umer , Flis Ilona , Howell Sue , McIntyre Jennifer , Gilleard John S. , Tait Andy , Mable Barbara , Kaplan Ray , Sargison Neil , Britton Collette , Berriman Matthew , Devaney Eileen , Cotton James A. 
Published: November 2021

AbstractUnderstanding the genetic basis of anthelmintic drug resistance in parasitic nematodes is key to improving the efficacy and sustainability of parasite control. Here, we use a genetic cross in a natural host-parasite system to simultaneously map resistance loci for the three major classes of anthelmintics. This approach identifies novel alleles for resistance to benzimidazoles and levamisole and implicates the transcription factor, cky-1, in ivermectin resistance. This gene is within a locus under selection in ivermectin resistant populations worldwide; functional validation using knockout experiments supports a role for cky-1 overexpression in ivermectin resistance. Our work demonstrates the feasibility of high-resolution forward genetics in a parasitic nematode, and identifies variants for the development of molecular diagnostics to combat drug resistance in the field.One-Sentence Summary:Genetic mapping of known and novel anthelmintic resistance-associated alleles in a multi-drug resistant parasitic nematode