bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airway epithelial interferon response to SARS-CoV-2 is inferior to rhinovirus and heterologous rhinovirus infection suppresses SARS-CoV-2 replication
Authors: Vanderwall Elizabeth R. , Barrow Kaitlyn A. , Rich Lucille M. , Read David F. , Trapnell Cole , Okoloko Oghenemega , Ziegler Steven F. , Hallstrand Teal S. , White Maria P. , Debley Jason S. 
Published: November 2021

ABSTRACTIntroductionCommon alphacoronaviruses and human rhinoviruses (HRV) induce type I and III interferon (IFN) responses important to limiting viral replication in the airway epithelium. In contrast, highly pathogenic betacoronaviruses including SARS-CoV-2 may evade or antagonize RNA-induced IFN I/III responses.MethodsIn airway epithelial cells (AECs) from children and older adults we compared IFN I/III responses to SARS-CoV-2 and HRV-16, and assessed whether pre-infection with HRV-16, or pretreatment with recombinant IFN-β or IFN-λ, modified SARS-CoV-2 replication. Bronchial AECs from children (ages 6-18 yrs.) and older adults (ages 60-75 yrs.) were differentiated ex vivo to generate organotypic cultures. In a biosafety level 3 (BSL-3) facility, cultures were infected with SARS-CoV-2 or HRV-16, and RNA and protein was harvested from cell lysates 96 hrs. following infection and supernatant was collected 48 and 96 hrs. following infection. In additional experiments cultures were pre-infected with HRV-16, or pre-treated with recombinant IFN-β1 or IFN-λ2 before SARS-CoV-2 infection.ResultsDespite significant between-donor heterogeneity SARS-CoV-2 replicated 100 times more efficiently than HRV-16. IFNB1, INFL2, and CXCL10 gene expression and protein production following HRV-16 infection was significantly greater than following SARS-CoV-2. IFN gene expression and protein production were inversely correlated with SARS-CoV-2 replication. Treatment of cultures with recombinant IFNβ1 or IFNλ2, or pre-infection of cultures with HRV-16, markedly reduced SARS-CoV-2 replication.DiscussionIn addition to marked between-donor heterogeneity in IFN responses and viral replication, SARS-CoV-2 elicits a less robust IFN response in primary AEC cultures than does rhinovirus, and heterologous rhinovirus infection, or treatment with recombinant IFN-β1 or IFN-λ2, markedly reduces SARS-CoV-2 replication.
Klebsiella pneumoniae mutants resistant to ceftazidime/avibactam plus aztreonam, imipenem/relebactam, meropenem/vaborbactam and cefepime/taniborbactam
Authors: Satapoomin Naphat , Dulyayangkul Punyawee , Avison Matthew B. 
Published: November 2021

ABSTRACTUsing modified Klebsiella pneumoniae clinical isolates, we show that ramR plus ompK36 mutation together with production of the V239G variant KPC-3 confirs resistance to ceftazidime/avibactam plus aztreonam, imipenem/relebactam and meropenem/vaborbactam, but not cefepime/taniborbactam. This is because the V239G variant does not generate collateral β-lactam susceptibility as do many other KPC-3 variants associated with ceftazidime/avibactam resistance. Additional mutation of ompK35 and carriage of a plasmid expressing the OXA-48-like carbapenemase OXA-232 was required to confer cefepime/taniborbactam resistance.
Patient brain organoids identify a link between the 16p11.2 copy number variant and the RBFOX1 gene
Authors: Kostic Milos , Raymond Joseph J. , Henry Beata , Tumkaya Tayfun , Khlghatyan Jivan , Dvornik Jill , Hsiao Jack S. , Cheon Seon Hye , Chung Jonathan , Sun Yishan , Dolmetsch Ricardo E. , Worringer Kathleen A. , Ihry Robert J. 
Published: November 2021

SUMMARYCopy number variants (CNVs) that delete or duplicate 30 genes within the 16p11.2 genomic region give rise to a range of neurodevelopmental phenotypes with high penetrance in humans. Despite the identification of this small region, the mechanisms by which 16p11.2 CNVs lead to disease are unclear. Relevant models, like human cortical organoids (hCOs), are needed to understand the human-specific mechanisms of neurodevelopmental disease. We generated hCOs from 18 patients and controls, profiling 167,958 cells with single cell (sc)RNA-seq. Analysis revealed neuronal-specific differential expression of genes outside of the 16p11.2 region that were related to cell-cell adhesion, neuronal projection growth, and neurodevelopmental disorders. Furthermore, 16p11.2 deletion syndrome organoids exhibited reduced mRNA and protein levels of RBFOX1, a gene which can also harbor CNVs linked to neurodevelopmental phenotypes. We found that many genes previously shown to be regulated by RBFOX1 are also perturbed in organoids from patients with 16p11.2 deletion syndrome, and thus identified a novel link between independent CNVs associated with neuronal development and autism. Overall, this work suggests convergent signaling, which indicates the possibility of a common therapeutic mechanism across multiple rare neuronal diseases.
Early age-related atrophy of cutaneous lymph nodes precipitates an early functional decline in skin immunity in mice with aging
Authors: Sonar Sandip Ashok , Uhrlaub Jennifer L. , Coplen Christopher P. , Sempowski Gregory D. , Dudakov Jarrod A. , van den Brink Marcel R.M. , LaFleur Bonnie J. , Jergovic Mladen , Nikolich-Žugich Janko 
Published: November 2021

ABSTRACTSecondary lymphoid organs (SLO; including the spleen and lymph nodes) are critical both for the maintenance of naïve T (TN) lymphocytes and for the initiation and coordination of immune responses. How they age, including the exact timing, extent, physiological relevance, and the nature of age-related changes, remains incompletely understood. We used time-stamping to indelibly mark cohorts of newly generated naïve T cells (a.k.a. recent thymic emigrants - RTE) in mice, and followed their presence, phenotype and retention in SLO. We found that SLO involute asynchronously. Skin-draining lymph nodes (LN) atrophied early (6-9 months) in life and deeper tissue-draining LN and the spleen late (18-20 months), as measured by the loss of both TN numbers and the fibroblastic reticular cell (FRC) network. Time-stamped RTE cohorts of all ages entered SLO and successfully completed post-thymic differentiation. However, in older mice, these cells were poorly retained, and those found in SLO exhibited an emigration phenotype (CCR7loS1P1hi). Transfers of adult RTE into recipients of different ages formally demonstrated that the defect segregates with the age of the SLO microenvironment and not with the age of T cells. Finally, upon intradermal immunization, RTE generated in mice as early as 6-7 months of age barely participated in de novo immune responses and failed to produce well-armed effector cells. These results highlight changes in structure and function of superficial secondary lymphoid organs in laboratory mice that are earlier than expected and are consistent with the long-appreciated and pronounced reduction of cutaneous immunity with aging.
The special and general mechanism of cyanobacterial harmful algal blooms
Authors: Cheng Wenduo , Hwang Somin , Guo Qisen , Qian Leyuan , Liu Weile , Yu Yang , Li Zhenghao , Wang Tianji , Tao Yi , Cao Huansheng 
Published: November 2021

AbstractCyanobacterial harmful algal blooms (CyanoHABs) arise as cyanobacteria dominate phytoplankton communities when nutrient levels increase from oligotrophic state. From a wholistic perspective, this longstanding altered phytoplankton structure results from two conditions: one sufficient condition that cyanobacteria can grow maximally with elevated nutrients; one necessary condition that co-living algae cannot grow fast or dominate at the same levels. The sufficient condition, the ‘special’ mechanism of CyanoHABs at the population level, has been established as the synergistic interaction between superior cyanobacterial ecophysiology and elevated nutrients. But it is unknown how these functions arise or whether they are under directed evolution to water eutrophication. The necessary condition, the ‘general’ mechanism of CyanoHABs at the community level, is little understood: why co-living algae cannot form blooms as cyanobacteria? Literature and bioinformatics analyses show that the superior ecophysiology undergoes no directed positive evolution to worldwide eutrophication in general or any local eutrophic waters in particular; instead, these functions are under strong purifying selection and likely acquired through early adaptive radiation in nutrient-deficient conditions, as functions enabling extant cyanobacteria to occupy other niches. The general mechanism turns out to be quite straightforward: cyanobacteria are simple life forms and thus have lower per capita nutrient demand for growth, compared to co-existing eukaryotic algae in cell size and structure, genome size, size of genome-scale metabolic networks, cell content, nutrient requirement. Lower nutrient demand is proved by existing field nutrient supplementation. Both the special and general mechanisms of CyanoHABs are tentative frameworks awaiting further theoretic improvement and empirical assessment.
Reconstruction and variability of tropical pollination networks in the Brazilian Atlantic Forest
Authors: Pereira Juliana , Battiston Federico , Ribeiro Milton Cezar , Jordán Ferenc 
Published: November 2021

AbstractLoss of biodiversity comprehends not only the extinction of individual species, but also the loss of the ecological interactions among them. Survival of species, continuation of ecosystem functioning in nature, and ecosystem services to humans depend on the maintenance of well-functioning networks of species interactions (e.g. plant-pollinator networks and food webs). Analyses of ecological networks often rely on biased and incomplete survey data, especially in species-rich areas, such as the tropics.We used a network inference method to reconstruct pollination data compiled from a large tropical rainforest habitat extent. To gain insight into the characteristics of plant-pollinator interactions across the region, we combined the reconstructed pollination network with species distribution modeling to obtain local pollination networks throughout the area. We explored how global network properties relate to natural forest cover and land cover heterogeneity.We found that some network properties (the sum and evenness of link weights, connectance and nestedness) are positively correlated with forest cover, indicating that networks in sites with more natural habitat have greater diversity of interactions, stability and resilience. Modularity was not related to forest cover, but seemed to reflect habitat heterogeneity, due to the broad spatial scale of the study.We believe that the methodology suggested here can facilitate the use of incomplete network data in a reliable way, and allow us to better understand and protect networks of species interactions in high biodiversity regions of the world.
Genome Assembly and Population Resequencing Reveal the Geographical Divergence of ‘Shanmei’ (Rubus corchorifolius)
Authors: Yang Yinqing , Zhang Kang , Xiao Ya , Zhang Lingkui , Huang Yile , Li Xing , Chen Shumin , Peng Yansong , Yang Shuhua , Liu Yongbo , Cheng Feng 
Published: November 2021

AbstractRubus corchorifolius(‘Shanmei’ or mountain berry, 2n =14) is widely distributed in China, and its fruit has high nutritional and medicinal values. Here, we report a high-quality chromosome-scalegenome assemblyof Shanmei, with a size of 215.69 Mb and encompassing 26,696 genes. Genome comparisons among Rosaceae species show that Shanmei and Fupenzi (Rubus chingiiHu) are most closely related, and then is blackberry (Rubus occidentalis). Furtherresequencingof 101 samples of Shanmei collected from four regions in provinces of Yunnan, Hunan, Jiangxi, and Sichuan in South China reveals that the Hunan population of Shanmei possesses the highest diversity and may represent the relatively more ancestral population. Moreover, the Yunnan population undergoes strong selection based on nucleotide diversity, linkage disequilibrium, and the historical effective population size analyses. Furthermore, genes from candidate genomic regions that show strongdivergenceare significantly enriched in flavonoid biosynthesis and plant hormone signal transduction, indicating the genetic basis of adaptation of Shanmei to the local environments. The high-quality genome sequences and the variome dataset of Shanmei provide valuable resources for breeding applications and for elucidating thegenome evolutionand ecological adaptation ofRubusspecies.
“Comparative genomics and pangenomics of vancomycin resistant and susceptibleEnterococcus faeciumfrom Irish hospitals across 20 years”
Authors: Leigh R.J. , McKenna C. , McWade R. , Lynch B. , Walsh F. 
Published: November 2021

AbstractEnterococcus faeciumhas emerged as an important nosocomial pathogen, which is increasingly difficult to treat due to the genetic acquisition of vancomycin resistance. Ireland exhibits a recalcitrant vancomycin resistant bloodstream infection rate compared to other developed countries. A set of 28 vancomycin resistant isolates was sequenced to construct a dataset alongside 61 other publicly available Irish genomes. This dataset was extensively analysed usingin-silicomethodologies and uncovered distinct evolutionary, coevolutionary, and clinically relevant population trends. These results suggest that a stable (in terms of genome size, GC%, and number of genes), yet genetically diverse population (in terms of gene content) ofEnterococcus faeciumpersist in Ireland with acquired resistance arisingviaplasmid acquisition (vanA) or to a lesser extent, chromosomal recombination (vanB). Population analysis described five clusters with one cluster partitioned into four clades which transcend isolation dates. Pangenomic and recombination analyses revealed an open (whole genome and chromosomal specific) pangenome illustrating a rampant evolutionary pattern. Comparative resistomics and virulomics uncovered distinct chromosomal and mobilomal propensity for multidrug resistance, widespread chromosomal point-mutation mediated resistance, and chromosomal harboured arsenals of virulence factors. Comparative phagomics revealed a core prophagome of three prophages throughout the dataset. Interestingly, a potential difference in biofilm formation strategies was highlighted by coevolutionary analysis, suggesting differential biofilm genotypes betweenvanAandvanBisolates. These results highlight the evolutionary history of IrishEnterococcus faeciumisolates and may provide an insight into underlying infection dynamics in a clinical setting.
Human visual gamma for color stimuli: When LGN drive is equalized, red is not special
Authors: Stauch Benjamin Johannes , Peter Alina , Ehrlich Isabelle , Nolte Zora , Fries Pascal 
Published: November 2021

SUMMARYStrong gamma-band oscillations in primate early visual cortex can be induced by spatially homogeneous, high-contrast stimuli, such as color surfaces. Compared to other hues, particularly strong gamma oscillations have been reported for red stimuli. However, precortical color processing and the resultant strength of input to V1 has often not been fully controlled for. This leaves the possibility that stronger responses to some hues were due to differences in V1 input strength. We presented stimuli that had equal luminance and color contrast levels in a color coordinate system based on color responses of the lateral geniculate nucleus, the main input source for area V1. With these stimuli, we recorded magnetoencephalography in 30 human subjects. We found narrowband color-induced gamma oscillations in early visual cortex, which, contrary to previous reports, did not differ between red and green stimuli of equal L-M cone contrast. Notably, blue stimuli with contrast exclusively on the S-cone axis induced very weak gamma responses, as well as smaller event-related fields and poorer change detection performance. The strength of human color gamma responses could be well explained by the strength of thalamic input induced by each hue and does not show a clear red bias when this input strength is properly equalized.
A Neurostimulator System for Real, Sham, and Multi-Target Transcranial Magnetic Stimulation
Authors: Sorkhabi Majid Memarian , Denison Timothy 
Published: November 2021

AbstractBackgroundTranscranial magnetic stimulation (TMS) is a clinically effective therapeutic instrument used to modulate neural activity. Despite three decades of research, two challenging issues remain, the possibility of changing the 1) stimulated spot and 2) stimulation type (real or sham) without physically moving the coil.ObjectiveIn this study, a second-generation programmable TMS (pTMS2) device with advanced stimulus shaping is introduced that uses a 5-level cascaded H-bridge inverter and phase-shifted pulse-width modulation (PWM). The principal idea of this research is to obtain real, sham, and multi-locus stimulation with the same TMS system.MethodsWe propose a two-channel modulation-based magnetic pulse generator and a novel coil arrangement, consisting of two circular coils with a physical distance of 20 mm between the coils and a control method for modifying the effective stimulus intensity, which leads to the live steerability of the location and type of stimulation.ResultsBased on the measured system performance, the stimulation profile can be steered ± 20 mm along a line from the centroid of the coil locations by modifying the modulation index.ConclusionThe proposed system supports electronic control of the stimulation spot without physical coil movement, resulting in tunable modulation of targets, which is a crucial step towards automated TMS machines.
Single organoid RNA-sequencing reveals high organoid-to-organoid variability
Authors: Gehling Kristin , Parekh Swati , Schneider Farina , Kirchner Marcel , Kondylis Vangelis , Nikopoulou Chrysa , Tessarz Peter 
Published: November 2021

ABSTRACTOver the last decades, organoids have been established from the majority of tissue resident stem and iPS cells. They hold great promise for our understanding of mammalian organ development, but also for the study of disease or even personalized medicine. In recent years, several reports hinted at intraculture organoid variability, but a systematic analysis of such a heterogeneity has not been performed before. Here, we used RNA-seq of individual organoids to address this question. Importantly, we find that batch-to-batch variation is very low, even when prepared by different researchers. On the other hand, there is organoid-to-organoid variability within a culture. Using differential gene expression, we did not identify specific pathways that drive this variability, pointing towards possible effects of the microenvironment within the culture condition. Taken together, our study provides a framework for organoid researchers to properly consider experimental design.
A metagenomic DNA sequencing assay that is robust against environmental DNA contamination
Authors: Mzava Omary , Cheng Alexandre Pellan , Chang Adrienne , Smalling Sami , Kounatse Liz-Audrey Djomnang , Lenz Joan , Longman Randy , Steadman Amy , Salvatore Mirella , Suthanthiran Manikkam , Lee John R. , Mason Christopher E. , Dadhania Darshana , De Vlaminck Iwijn 
Published: November 2021

ABSTRACTMetagenomic DNA sequencing is a powerful tool to characterize microbial communities but is sensitive to environmental DNA contamination, in particular when applied to samples with low microbial biomass. Here, we present contamination-free metagenomic DNA sequencing (Coffee-seq), a metagenomic sequencing assay that is robust against environmental contamination. The core idea of Coffee-seq is to tag the DNA in the sample prior to DNA isolation and library preparation with a label that can be recorded by DNA sequencing. Any contaminating DNA that is introduced in the sample after tagging can then be bioinformatically identified and removed. We applied Coffee-seq to screen for infections from microorganisms with low burden in blood and urine, to identify COVID-19 co-infection, to characterize the urinary microbiome, and to identify microbial DNA signatures of inflammatory bowel disease in blood.
Increased heterogeneity and task-related reconfiguration of functional connectivity within a lexicosemantic network in autism
Authors: Sridhar Apeksha , Keehn R. Joanne Jao , Wilkinson Molly , Gao Yangfeifei , Olson Michael , Mash Lisa E , Alemu Kalekirstos , Manley Ashley , Marinkovic Ksenija , Linke Annika , Müller Ralph-Axel 
Published: November 2021

AbstractAutism spectrum disorder (ASD) is highly heterogeneous in etiology and clinical presentation. Findings on intrinsic functional connectivity (FC) or task-induced FC in ASD have been inconsistent including both over- and underconnectivity and diverse regional patterns. As FC patterns change across different cognitive demands, a novel and more comprehensive approach to network architecture in ASD is to examine the change in FC patterns between rest and task states, referred to as reconfiguration. This approach is suitable for investigating inefficient network connectivity that may underlie impaired behavioral functioning in clinical disorders. We used functional magnetic resonance imaging (fMRI) to examine FC reconfiguration during lexical processing, which is often affected in ASD, with additional focus on interindividual variability. Thirty adolescents with ASD and a matched group of 23 typically developing (TD) participants completed a lexicosemantic decision task during fMRI, using multiecho-multiband pulse sequences with advanced BOLD signal sensitivity and artifact removal. Regions of interest (ROIs) were selected based on task-related activation across both groups, and FC and reconfiguration were compared between groups. The ASD group showed increased interindividual variability and overall greater reconfiguration than the TD group. An ASD subgroup with typical performance accuracy (at the level of TD participants) showed reduced similarity and typicality of FC during the task. In this ASD subgroup, greater FC reconfiguration was associated with increased language skills. Findings suggest that intrinsic functional networks in ASD may be inefficiently organized for lexicosemantic decisions and may require greater reconfiguration during task processing, with high performance levels in some individuals being achieved through idiosyncratic mechanisms.HighlightsFC reconfiguration is a comprehensive approach to examining network architectureFunctional networks are inefficiently organized for lexicosemantic decisions in ASDASD may require greater reconfiguration during task processingSome ASD individuals achieve high performance through idiosyncratic mechanisms
Thermodynamic Constraints on Electromicrobial Protein Production
Authors: Wise Lucas , Marecos Sabrina , Randolph Katie , Nshimyumukiza Eric , Hassan Mohamed , Strouse Jacob , Salimijazi Farshid , Barstow Buz 
Published: November 2021

AbstractGlobal consumption of protein is projected to double by the middle of the 21st century1. However, protein production is one of the most energy intensive and environmentally damaging parts of the food supply system today. Electromicrobial production technologies that combine renewable electricity and CO2-fixing microbial metabolism could dramatically increase the energy efficiency of commodity chemical production2–5. Here we present a molecular-scale model that sets an upper limit on the performance of any organism performing electromicrobial protein production. We show that engineered microbes that fix CO2 and N2 using reducing equivalents produced by H2-oxidation or extracellular electron uptake could produce amino acids with energy inputs as low as 64 MJ kg-1. This work provides a roadmap for development of engineered microbes that could significantly expand access to proteins produced with a low environmental footprint.