bluuebunny/crossref_metadata_2025_split huggingface dataset:
AMycobacterium tuberculosiseffector protein attacks host innate immunity by acting as an unusual ubiquitinating enzyme
Authors: Wang Jing , Ge Pupu , Lei Zehui , Lu Zhe , Qiang Lihua , Chai Qiyao , Zhang Yong , Zhao Dongdong , Li Bingxi , Su Jiaqi , Peng Ruchao , Pang Yu , Shi Yi , Gao George Fu , Qiu Xiao-Bo , Liu Cui Hua 
Published: November 2020

AbstractProtein kinase G (PknG), a eukaryotic type serine-threonine protein kinase (STPK) inMycobacterium tuberculosis(Mtb), is secreted into the cytosol of infected macrophages to promote intracellular survival of mycobacteria and has been considered as a promising therapeutic target for tuberculosis (TB) treatment. However, the molecular details of Mtb PknG-host intracellular interactions remain obscure. Here, we demonstrate that PknG serves as both the ubiquitin-activating enzyme (E1) and the ubiquitin ligase (E3) to promote ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF–β-activated kinase 1 (TAK1), and thus inhibits the NF-κB-mediated host innate immune responses. Surprisingly, PknG promotes the attachment of ubiquitin (Ub) to ubiquitin-conjugating enzyme (E2) UbcH7 via an isopeptide bond (UbcH7 K82-Ub), instead of a usual C86-Ub thiol-ester bond, and then promotes the discharge of Ub from UbcH7 by acting as an isopeptidase before attaching Ub to its substrates TRAF2 and TAK1. These results demonstrate that Mtb PknG promotes ubiquitination of the key components of the host innate immunity by acting as an unusual ubiquitinating enzyme to suppress innate immunity. Our findings provide a potential TB treatment via targeting unconventional ubiquitinating activities of PknG.SignificanceMycobacterium tuberculosis(Mtb) protein kinase G (PknG), which is critical for Mtb intracellular survival, is a promising target for tuberculosis (TB) treatment. However, the molecular mechanisms underlying PknG-host interactions remain largely unclear. Here we demonstrate that PknG serves as both the ubiquitin-activating enzyme and the ubiquitin ligase to promote the ubiquitination and degradation of tumor necrosis factor receptor-associated factor 2 (TRAF2) and TGF-β-activated kinase 1 (TAK1), thus inhibiting NF-κB signaling activation. PknG promotes the attachment of ubiquitin to ubiquitin-conjugating enzyme UbcH7 via an isopeptide bond, instead of a usual thiol-ester bond, and releases the ubiquitin from UbcH7 by acting as an isopeptidase. These findings provide important information for rational development of TB treatment via targeting unconventional ubiquitinating activity of PknG.
Effects of faecal inorganic contents in accurate measures of stress and nutrition hormone in large felines: implications for physiological assessments in free-ranging animals
Authors: Patel Shiv Kumari , Biswas Suvankar , Goswami Sitendu , Bhatt Supriya , Pandav Bivash , Mondol Samrat 
Published: November 2020

AbstractNon-invasive stress and nutritional hormones and their interactions are increasingly being used to monitor psychological and nutritional physiology in free-ranging animals at different ecological scales. However, a number of extrinsic and intrinsic factors including hormone-inert dietary materials, inorganic matters etc. are known to affect accurate hormone measures. Here we addressed the impacts of inorganic matter (IOM) on corticosterone and T3 measures in wild tiger (n=193 from Terai Arc landscape, India) and captive lion (n=120 from Sakkarbaug Zoological Garden, Gujarat, India) faeces and evaluated possible corrective measures. The wild tiger samples contained highly variable IOM content (9-98%, mostly with >40% IOM) compared to captive Asiatic lion (17-57%, majority with <40% IOM). We observed significant negative correlation between IOM content and tiger GC (r=−0.48, p=0.000) and T3 (r=−0.60, p=0.000) measures but not in captive lions (r=−0.05, p=0.579). Two corrective measures viz. removing samples with ≥80% IOM and subsequently expressing concentrations as per gram of organic dry matter (instead of total dry matter) reduced IOM influence on tiger GC and T3 measures without affecting lion GC results. The corrective measures bring out alterations in the tiger T3 results but no changes in GC results. As faecal IOM content is associated with specific behaviours of many carnivore species, our results emphasize the need to reduce IOM-driven hormone data variation for ecologically relevant interpretations for species conservation.
Arenavirus nucleoprotein localizes to mitochondria
Authors: Baggio Francesca , Hetzel Udo , Nufer Lisbeth , Kipar Anja , Hepojoki Jussi 
Published: November 2020

ABSTRACTViruses need cells to replicate and, therefore, ways to counteract the host’s immune response. Mitochondria play central roles in mediating innate immunity, hence some viruses have developed mechanisms to alter mitochondrial functions. Herein we show that arenavirus nucleoprotein (NP) enters the mitochondria of infected cells and affects their morphological integrity. We initially demonstrate electron-dense inclusions within mitochondria of reptarenavirus infected cells and hypothesized that these represent viral NP. Software predictions then serve to identify a putative N-terminal mitochondrial targeting signal (MTS) in arenavirus NPs; however, comparisons of wild-type and N-terminus mutated NPs suggest MTS-independent mitochondrial entry. NP does not enter isolated mitochondria, indicating that translocation requires additional cellular factors or conditions. Immune electron microscopy finally confirms the presence of NP within the mitochondria bothin vitroand in infected animals. We hypothesize that mitochondria targeting might complement the known interferon antagonist functions of NP or alter the cell’s metabolic state.
Decomposing the role of alpha oscillations during brain maturation
Authors: Tröndle Marius , Popov Tzvetan , Dziemian Sabine , Langer Nicolas 
Published: November 2020

AbstractChildhood and adolescence are critical stages of the human lifespan, in which fundamental neural reorganizational processes take place. A substantial body of literature investigated neurophysiological changes during brain maturation by focusing on the most dominant feature of the human EEG signal: the alpha oscillation. Ambiguous results were reported for the developmental trajectory of the power of the alpha oscillation. Simulations in this study show that conventional measures of alpha power are confounded by various factors and need to be decomposed into periodic and aperiodic components, which represent distinct underlying brain mechanisms. It is therefore unclear how each part of the signal relates to changes during brain maturation. Using multivariate Bayesian generalized linear mixed models, we examined aperiodic and periodic parameters of alpha activity in the largest openly available pediatric dataset (N=2529, age range 5-21 years) and replicated these findings in a preregistered analysis of an independent validation sample (N=369, age range 6–21yrs). First, the well documented age-related decrease in total alpha power was replicated. However, when controlling for the aperiodic signal component, our findings provide strong evidence for a reversed developmental trajectory of the periodic alpha power, whereas the aperiodic signal components, slope and offset, decreased. Consequently, earlier interpretations on age related changes of alpha power need to be fundamentally reconsidered, incorporating changes in the aperiodic signal. The interpretation of decreased total alpha power as elimination of active synapses rather links to decreases in the aperiodic intercept. Instead, additional analyses of diffusion tensor imaging data indicate that the maturational increase in periodic alpha power is related to increased thalamocortical connectivity. Functionally, our results suggest that increased thalamic control of cortical alpha power is linked to improved attentional performance during brain maturation.
Extraction and Characterization of Rice Bran Polysaccharides and Their Derivative Preparation and Antioxidant Activity
Authors: Huang Gangliang 
Published: November 2020

AbstractThe crude polysaccharide of rice bran polysaccharide was extracted with water from defatted rice bran, and the optimal reaction conditions of the experiment were determined. The reaction temperature is 100°C, the reaction time is 5h, the solid-liquid ratio is 1:10; the concentration ratio of polysaccharide to Sevag reagent is 2:1, and rice polysaccharide is precipitated by ethanol insoluble property and ethanol. The ethanol concentration ratio is 3:1. Using the methods and conditions of this experiment, the maximum polysaccharide yield is 2.18%. Then the chemical structure of rice bran polysaccharide was analyzed by IR, UV and 13CNMR methods. Three rice bran polysaccharide derivatives were prepared and characterized: carboxymethylated rice bran polysaccharide, phosphorylated rice bran polysaccharide and acetylated rice bran polysaccharide. Also studied the antioxidant activity of rice bran polysaccharide and its derivatives (hydroxy radical ion scavenging ability, superoxide anion scavenging ability, anti-lipid peroxidation ability, reducing ability), and found that phosphorylated rice bran polysaccharide has good activity. The acetylated rice bran polysaccharide may weaken the original activity.
Age-dependent contribution of domain-general networks to semantic cognition
Authors: Martin Sandra , Saur Dorothee , Hartwigsen Gesa 
Published: November 2020

AbstractAging is characterized by a decline of cognitive control. In semantic cognition, this leads to the paradox that older adults usually show poorer task performance than young adults despite their greater semantic knowledge. So far, the underlying neural changes of these behavioral differences are poorly understood. In the current neuroimaging study, we investigated the contribution of domain-general networks to a verbal semantic fluency task in young and older adults. In both age groups, task processing was characterized by a strong positive integration within the multiple-demand as well as between the multiple-demand and the default mode system during semantic fluency. However, the behavioral relevance of strengthened connectivity differed between groups: While within-network functional connectivity in both networks predicted greater efficiency in semantic fluency in young adults, it was associated with a slower performance in older adults. Moreover, only young adults profited from increased connectivity between networks for their semantic memory performance. Our results suggest that the functional coupling of usually anti-correlated networks is critical for successful task processing, independent of age, when access to semantic memory is required. Furthermore, our findings lend novel support to the notion of reduced efficiency in the aging brain, due to neural dedifferentiation in semantic cognition.
Single gene targeted nanopore sequencing enables simultaneous identification and antimicrobial resistance detection of sexually transmitted infections
Authors: Zhou Liqing , Rodas Andrea Lopez , Llangarí Luz Marina , Sandoval Natalia Romero , Cooper Philip , Sadiq Syed Tariq 
Published: November 2020

AbstractObjectivesTo develop a simple DNA sequencing test for simultaneous identification and antimicrobial resistance (AMR) detection of multiple sexually transmitted infections (STIs).MethodsReal-time PCR (qPCR) was initially performed to identifyNeisseria gonorrhoeae(NG),Chlamydia trachomatis(CT),Mycoplasma genitalium(MG) andTrichomonas vaginalis(TV) infections among a total of 200 vulvo-vaginal swab samples from female sex workers in Ecuador. qPCR positive samples plus qPCR negative controls for these STIs were subjected to single gene targeted PCR MinION-nanopore sequencing using the smartphone operated MinIT.ResultsAmong 200 vulvo-vaginal swab samples 43 were qPCR positive for at least one of the STIs. Single gene targeted nanopore sequencing generally yielded higher pathogen specific read counts in qPCR positive samples than qPCR negative controls. Of the 26 CT, NG or MG infections identified by qPCR, 25 were clearly distinguishable from qPCR negative controls by read count. Discrimination of TV qPCR positives from qPCR negative controls was poorer as many had low pathogen loads (qPCR cycle threshold >35) which produced few specific reads. Real-time AMR profiling revealed that 3/3 NG samples identified hadgyrAmutations associated with fluoroquinolone resistance, while none of the MG samples possessed23S rRNAgene mutations contributing to macrolide resistance.ConclusionsSingle gene targeted nanopore sequencing for diagnosing and simultaneously identifying key antimicrobial resistance markers for four common genital STIs shows promise. Further work to optimise accuracy, reduce costs and improve speed may allow sustainable approaches for managing STIs and emerging AMR in resource poor and laboratory limited settings.
Matchathon: A guide to student-faculty connections in PhD programs
Authors: Amemiya Haley , Lapp Zena , Smith Cathy , Durdan Margaret , DiMondo Michelle , Bodiya Beth , Barolo Scott 
Published: November 2020

AbstractRelevant and impactful mentors are essential to a graduate student’s career. Finding mentors can be challenging in umbrella programs with hundreds of faculty members. To foster connections between potential mentors and students with similar research interests, we created a Matchathon event, which has successfully enabled students to find mentors. We developed an easy-to-use R Shiny app (https://github.com/UM-OGPS/matchathon/) to facilitate matching and organizing the event that can be used at any institution. It is our hope that this resource will improve the environment and retention rates for students in the academy.The open source app is publicly available on the web (app:https://UM-OGPS.shinyapps.io/matchathon/; source code:https://github.com/UM-OGPS/matchathon/).
Identification of Fibronectin 1 as a candidate genetic modifier in aCol4a1mutant mouse model of Gould syndrome
Authors: Mao Mao , Popli Tanav , Jeanne Marion , Hoff Kendall , Sen Saunak , Gould Douglas B. 
Published: November 2020

ABSTRACTCollagen type IV alpha 1 and alpha 2 (COL4A1 and COL4A2) are major components of almost all basement membranes.COL4A1andCOL4A2mutations cause a multisystem disorder called Gould syndrome which can affect any organ but typically involves the cerebral vasculature, eyes, kidneys and skeletal muscles. The manifestations of Gould syndrome are highly variable and animal studies suggest that allelic heterogeneity and genetic context contribute to the clinical variability. We previously characterized a mouse model of Gould syndrome caused by aCol4a1mutation in which the severities of ocular anterior segment dysgenesis (ASD), myopathy, and intracerebral hemorrhage (ICH) were dependent on genetic background. Here, we performed a genetic modifier screen to provide insight into the mechanisms contributing to Gould syndrome pathogenesis and identified a single locus (modifier of Gould syndrome 1;MoGS1) on Chromosome 1 that suppressed ASD. A separate screen showed that the same locus ameliorated myopathy. Interestingly,MoGS1had no effect on ICH, suggesting that this phenotype may be mechanistically distinct. We refined theMoGS1locus to a 4.3 Mb interval containing 18 protein coding genes, includingFn1which encodes the extracellular matrix component fibronectin 1. Molecular analysis showed that theMoGS1locus increasedFn1expression raising the possibility that suppression is achieved through a compensatory extracellular mechanism. Furthermore, we show evidence of increased integrin linked kinase levels and focal adhesion kinase phosphorylation inCol4a1mutant mice that is partially restored by theMoGS1locus implicating the involvement of integrin signaling. Taken together, our results suggest that tissue-specific mechanistic heterogeneity contributes to the variable expressivity of Gould syndrome and that perturbations in integrin signaling may play a role in ocular and muscular manifestations.
Price equation captures the role of drug interactions and collateral effects in the evolution of multidrug resistance
Authors: Gjini Erida , Wood Kevin B. 
Published: November 2020

AbstractBacterial adaptation to antibiotic combinations depends on the joint inhibitory effects of the two drugs (drug interaction, DI) and how resistance to one drug impacts resistance to the other (collateral effects, CE). Here we model these evolutionary dynamics on two-dimensional phenotype spaces that leverage scaling relations between the drug-response surfaces of drug sensitive (ancestral) and drug resistant (mutant) populations. We show that evolved resistance to the component drugs–and in turn, the adaptation of growth rate–is governed by a Price equation whose covariance terms encode geometric features of both the two-drug response surface (DI) in ancestral cells and the correlations between resistance levels to those drugs (CE). Within this framework, mean evolutionary trajectories reduce to a type of weighted gradient dynamics, with the drug interaction dictating the shape of the underlying landscape and the collateral effects constraining the motion on those landscapes. Our results clarify the complex relationship between drug interactions and collateral effects in multi-drug environments and illustrate how specific dosage combinations can shift the weighting of these two effects, leading to different and temporally-explicit selective outcomes.
Predatory selection of mucoid, antibiotic resistantPseudomonas putidaphenotype by myxobacteriumCystobacter ferrugineus
Authors: Akbar Shukria , Stevens D. Cole 
Published: November 2020

AbstractPredation contributes to the structure and diversity of microbial communities. Predatory myxobacteria are ubiquitous to a variety of microbial habitats and capably consume a broad diversity of microbial prey. Predator-prey experiments utilizing myxobacteria have provided details into predatory mechanisms and features that facilitate consumption of prey. However, prey resistance to myxobacterial predation remains underexplored, and prey resistances have been observed exclusively from predator-prey experiments that included the model myxobacteriumMyxococcus xanthus.Utilizing a predator-prey pairing that instead included the myxobacterium,Cystobacter ferrugineus,withPseudomonas putidaas prey, we infrequently observed surviving phenotypes capable of eluding predation. Comparative transcriptomics betweenP. putidaunexposed toC. ferrugineusand the survivor phenotype suggested that increased expression of efflux pumps, genes associated with mucoid conversion, and various membrane features contribute to predator avoidance. TheP. putidasurvivor phenotype was confirmed to be resistant to the antibiotics kanamycin, gentamicin, and tetracycline and to produce more alginate, pyoveridine, and phenazine-1-carboxylic acid than predator-unexposedP. putida. Unique features observed from the survivor phenotype including small colony variation, efflux-mediated antibiotic resistance, phenazine-1-carboxylic acid production, and increased mucoid conversion overlap with traits associated withPseudomonas aeruginosapredator avoidance and pathogenicity. The survivor phenotype also benefited from increased predator resistance during subsequent predation assays. These results demonstrate the utility of myxobacterial predator-prey models and provide insight into prey resistances in response to predatory stress might contribute to the phenotypic diversity and structure of bacterial communities.
Fluorescent Antibody Multiplexing with Oligo-Based Combinatorial Labeling
Authors: McCarthy Madeline , Anglin Caitlin , Peer Heather , Boleman Sevanna , Klaubert Stephanie , Birtwistle Marc R. 
Published: November 2020

AbstractFluorescent antibodies are a workhorse of biomedical science, but fluorescence multiplexing has been notoriously difficult due to spectral overlap between fluorophores. We recently established proof-of-principal for fluorescence Multiplexing using Spectral Imaging and Combinatorics (MuSIC), which uses combinations of existing fluorophores to create unique spectral signatures for increased multiplexing. However, a method for labeling antibodies with MuSIC probes has not yet been developed. Here, we present a method for labeling antibodies with MuSIC probes. We conjugate a DBCO-Peg5-NHS ester linker to antibodies, a single stranded DNA “docking strand” to the linker, and finally, hybridize two MuSIC-compatible, fluorescently-labeled oligos to the docking strand. We validate the labeling protocol with spin-column purification and absorbance measurements, which show a degree of labeling of ~9.66 linker molecules / antibody. We demonstrate the approach using (i) Cy3, (ii) Tex615, and (iii) a Cy3-Tex615 combination as three different MuSIC probes attached to three separate batches of antibodies. We incubated MuSIC probe-labeled antibodies with protein A beads to create single and double positive beads that are analogous to single cells. Spectral flow cytometry experiments demonstrate that each MuSIC probe can be uniquely distinguished, and the fraction of beads in a mixture with different staining patterns is accurately measured. The approach is general and might be more broadly applied to cell type profiling or tissue heterogeneity studies in clinical, biomedical, and drug discovery research.
The spatial-temporal dynamics of respiratory syncytial virus infections across the east-west coasts of Australia during 2016-17
Authors: Robertson Mark , Eden John-Sebastian , Levy Avram , Carter Ian , Tulloch Rachel L , Cutmore Elena J , Horsburgh Bethany A , Sikazwe Chisha T , Dwyer Dominic E , Smith David W , Kok Jen 
Published: November 2020

AbstractRespiratory syncytial virus (RSV) is an important human respiratory pathogen. In temperate regions a distinct seasonality is observed, where peaks of infections typically occur in early winter, often preceding the annual influenza season. Infections are associated with high rates of morbidity and mortality, and in some populations exceeds that of influenza. Two subtypes, RSV-A and RSV-B, have been described, and molecular epidemiological studies have shown that both viruses mostly co-circulate. This trend also appears to be the case for Australia, however previous genomic studies have been limited to cases from one Eastern state - New South Wales. As such, the broader spatial patterns and viral traffic networks across the continent are not known. Here, we conducted a whole genome study of RSV comparing strains across eastern and western Australia during the period January 2016 to June 2017. In total, 96 new RSV genomes were sequenced, compiled with previously generated data, and examined using a phylodynamic approach. This analysis revealed that both RSV-A and RSV-B strains were circulating, and each subtype was dominated by a single genotype, RSV-A/ON1-like and RSV-B/BA10-like viruses. Some geographical clustering was evident in strains from both states with multiple distinct sub-lineages observed and relatively low mixing across jurisdictions suggesting that endemic transmission was likely seeded from imported, unsampled locations. Overall, the RSV phylogenies reflected a complex pattern of interactions across multiple epidemiological scales from fluid virus traffic across global and regional networks to fine-scale local transmission events.