bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial synaptic pruning on axon initial segment of dentate granule cells: sexually dimorphic effects on fear response of adult rats subjected to early life stress
Authors: Zetter Mario A. , Roque Angélica , Hernández Vito S. , Hernández-Pérez Oscar R. , Gómora María J. , Ruiz-Velasco Silvia , Eiden Lee E. , Zhang Limei 
Published: October 2020

AbstractAxon initial segments (AIS) of dentate granule cells (GC) in hippocampus exhibit prominent spines during early development that are associated with microglial contacts. Here, we asked if developmental changes in axon initial segment spines (AISS) could be modified by neonatal maternal separation through stress hormones and microglial activation and examined the potential behavioral consequences. We examined AISS densities at postnatal day (PND) 15 and 50, using Golgi-Cox staining and anatomical analysis. Neuron-microglial interaction was assessed using antibodies against ankyrinG, PSD95 and Iba1, for AIS, AISS and microglia, respectively, in normally reared and neonatal maternally separated (MS) male and female rats. We observed a higher density of AISS in MS groups at both PND15 and PND50 compared to control. Effects were more pronounced in female than in male rats. AIS-associated microglia showed a hyper-ramified morphology and less co-localization with PSD95 in MS compared to normally reared animals at PND 15. An MS-like alteration in microglial morphology and synaptic pruning could be produced ex vivo by vasopressin application in acute hippocampal slices from normally reared animals. MS rats exhibited increased freezing behavior during auditory fear memory testing which, like effects on AISS density, was more pronounced in females than males. Freezing behavior was associated with Fos expression in dorsal and ventral dentate GC. In summary, AIS associated microglial activity is altered by MS. Sex differences in the long-term effects of MS on AISS density are penetrant to a behavioral phenotype of increased stimulus reactivity in adult female subjects.
Identification ofAcinetobacter baumanniiand detection of ß - lactam antibiotic resistance genes in clinical samples by multiplex PCR
Authors: Phan-Canh Trinh , Le-Thi-Thanh Thao , Ngo-Thi-Bich Thuy , Nguyen-Thi-Thanh Thanh , Ho-Le-Truc Linh , Nguyen Tu-Anh 
Published: October 2020

AbstractAcinetobacter baumanniiis the leading cause of hospital-acquired infection in Vietnam. Of note, antibiotic resistance genes are significantly popular in clinical isolates ofA. baumannii. Therefore, rapid identification ofA. baumanniiand determination of antibiotic resistance genes will help to make effective clinical decisions related to antibiotic use. This paper proposes a multiplex PCR to identifyAcinetobacter baumanniiand detect their ß-lactam antibiotic resistance genes in clinical isolates. Multiplex PCR was applied to amplifiedrecA gene and region ITS 16S - 23S rDNA for Rapid detection ofA. baumannii.The two antibiotic resistance genes -blaOXA-51-like,ampC gene - were detected by multiplex PCR and three genes coding Extended-spectrum beta-lactamases -blaCTX-M,blaTEM,blaSHVgenes - were subjected to PCR. 49 bacteria strains were subjected to colony PCR. The result showed that 46 strains wereA. baumanniiand 3 strains belonged to the genusAcinetobacter.The multiplex PCR showed that all of 46A. baumanniicontaining theblaOXA-51-likegene and theAmpC gene; 34 strains possess the geneblaTEMand none of them hasblaCTX-MandblaSHVgenes. The results of the multiplex PCR are the same as those of thein vitroantibiotic sensitivity testing ofA. baumannii. However, applying the multiplex PCR directly from the bacteria colony, we can proceed simultaneously with the bacterial identification and the antibiotic resistance gene detection.Highlights100% of isolates ofA. baumanniicontains theblaOXA-51-likegene and theAmpC gene.34/46 isolates possess the geneblaTEM, however, do not containblaCTX-MandblaSHVgenes.Combined disc test with cefotaxime/clavulanic acid/boronic acid is an excellent method to analyse ESBL phenotype.
Diffusion-Informed Spatial Smoothing of fMRI Data in White Matter Using Spectral Graph Filters
Authors: Abramian David , Larsson Martin , Eklund Anders , Aganj Iman , Westin Carl-Fredrik , Behjat Hamid 
Published: October 2020

AbstractBrain activation mapping using functional magnetic resonance imaging (fMRI) has been extensively studied in brain gray matter (GM), whereas in large disregarded for probing white matter (WM). This unbalanced treatment has been in part due to controversies in relation to the nature of the blood oxygenation level-dependent (BOLD) contrast in WM and its detachability. However, an accumulating body of studies has provided solid evidence of the functional significance of the BOLD signal in WM and has revealed that it exhibits anisotropic spatio-temporal correlations and structure-specific fluctuations concomitant with those of the cortical BOLD signal. In this work, we present an anisotropic spatial filtering scheme for smoothing fMRI data in WM that accounts for known spatial constraints on the BOLD signal in WM. In particular, the spatial correlation structure of the BOLD signal in WM is highly anisotropic and closely linked to local axonal structure in terms of shape and orientation, suggesting that isotropic Gaussian filters conventionally used for smoothing fMRI data are inadequate for denoising the BOLD signal in WM. The fundamental element in the proposed method is a graph-based description of WM that encodes the underlying anisotropy observed across WM, derived from diffusion-weighted MRI data. Based on this representation, and leveraging graph signal processing principles, we design subject-specific spatial filters that adapt to a subject’s unique WM structure at each position in the WM that they are applied at. We use the proposed filters to spatially smooth fMRI data in WM, as an alternative to the conventional practice of using isotropic Gaussian filters. We test the proposed filtering approach on two sets of simulated phantoms, showcasing its greater sensitivity and specificity for the detection of slender anisotropic activations, compared to that achieved with isotropic Gaussian filters. We also present WM activation mapping results on the Human Connectome Project’s 100-unrelated subject dataset, across seven functional tasks, showing that the proposed method enables the detection of streamline-like activations within axonal bundles.
AP-4 mediates vesicular transport of the 2-AG endocannabinoid producing enzyme DAGLB
Authors: Davies Alexandra K. , Ziegler Marvin , Jumo Hellen , Saber Wardiya Afshar , Ebrahimi-Fakhari Darius , Borner Georg H. H. 
Published: October 2020

AbstractThe adaptor protein complex AP-4 mediates anterograde axonal transport and is essential for axon health. AP-4-deficient patients suffer from a severe neurological disorder, which encompasses neurodevelopmental and neurodegenerative features. While impaired autophagy has been suggested to account for axon degeneration in AP-4 deficiency, axon growth defects occur through an unknown mechanism. Here we use orthogonal proteomic and imaging methods to identify DAGLB (diacylglycerol lipase-beta) as a cargo of AP-4 vesicles. DAGLB is a key enzyme for the generation of 2-AG (2-arachidonoylglycerol), the most abundant endocannabinoid in brain. During normal development, DAGLB is targeted to the axon, where 2-AG signalling drives axonal growth. We show that DAGLB accumulates at the TGN of AP-4-deficient cells, including in iPSC-derived neurons from a patient with AP-4 deficiency syndrome. Our data thus support that AP-4 mediates axonal targeting of DAGLB, and we propose that axon growth defects in AP-4 deficiency may arise through spatial dysregulation of endocannabinoid signalling.
Trip duration drives shift in travel network structure with implications for the predictability of spatial disease spread
Authors: Giles John R , Cummings Derek AT , Grenfell Bryan T , Tatem Andrew J , Erbach-Schoenberg Elisabeth zu , Metcalf CJE , Wesolowski Amy 
Published: October 2020

AbstractHuman travel is one of the primary drivers of infectious disease spread. Models of travel are often used that assume the amount of travel to a specific destination decays as cost of travel increases and higher travel volumes to more populated destinations. Trip duration, the length of time spent in a destination, can also impact travel patterns. We investigated the spatial distribution of travel conditioned on trip duration and find distinct differences between short and long duration trips. In short-trip duration travel networks, trips are skewed towards urban destinations, compared with long-trip duration networks where travel is more evenly spread among locations. Using gravity models imbedded in simulations of disease transmission, we show that pathogens with shorter generation times exhibit initial patterns of spatial propagation that are more predictable among urban locations, whereas longer generation time pathogens have more diffusive patterns of spatial spread reflecting more unpredictable disease dynamics.
The psychological impact of coronavirus on university students and its socio-economic determinants in Malaysia
Authors: Irfan Muhammad , Shahudin Faizah , Hooper Vincent James , Akram Waqar , Abdul Ghani Rosmaiza Binti 
Published: October 2020

AbstractThis article examines the impact of coronavirus disease 2019 (COVID-19) upon university students’ anxiety level and finds the factors associated with the anxiety disorder in Malaysia. We collected data from 958 students from 16 different universities using an originally designed questionnaire. The Generalized Anxiety Disorder Scale 7-item (GAD-7) was used to estimate the anxiety. We find that 12.3% students were normal, whereas 30.5% were experiencing mild, 31.1% moderate, and 26.1% severe anxiety. Surprisingly, only 37.2% of students were aware of mental health support which was provided by their universities. Moreover, it was found that gender as male (Odds Ratio (OR= 0.798, 95% Confidence Interval (CI)= 0.61 - 1.04)) and having internet access (OR = 0.44, 95% CI= 0.24 - 0.80) were alleviating factors for the anxiety. Whereas, age above than 20 years (OR= 1.30, 95% CI= 0.96 - 1.75), ethnicity Chinese (OR=1.72, 95% CI= 0.95 - 3.1), any other disease (OR=2.0, 95% CI=1.44 - 2.79), decreased family income (OR=1.71, 95% CI=1.34 - 2.17), more time spent on watching COVID-19 related news (OR=1.52, 95% CI=1.17 - 1.97), and infected relative or friends (OR=1.62, 95% CI=1.06 - 2.50) were risk factors for anxiety among students. We suggest that the government of Malaysia should monitor the mental health of the universities’ students more closely and universities should open online mental health support clinics to avoid the adverse impacts of the anxiety disorder.
Possible changes in fidelity of DNA polymerase δ in ancestral mammals
Authors: Katoh Kazutaka , Iwabe Naoyuki , Miyata Takashi 
Published: October 2020

AbstractDNA polymerase δ (polδ) is one of the major DNA polymerases that replicate chromosomal genomes in eukaryotes. Given the essential role of this protein, its phylogenetic tree was expected to reflect the relationship between taxa, like many other essential proteins. However, the tree of the catalytic subunit of polδ showed an unexpectedly strong heterogeneity among vertebrate lineages in evolutionary rate at the amino acid level, suggesting unusual amino acid substitutions specifically in the ancestral mammalian lineage. Structural and phylogenetic analyses were used to pinpoint where and when these amino acid substitutions occurred: around the 3′-5′ exonuclease domain in later mammal ancestry, after the split between monotremes and therians. The 3′-5′ exonuclease domain of this protein is known to have an impact on the fidelity of replication. Based on these observations, we explored the possibility that the amino acid substitutions we identified in polδ affected the mutation rate of entire chromosomal genomes in this time period.
Genomic and microscopic evidence of stable high density and maternally inheritedWolbachiainfections inAnophelesmosquitoes
Authors: Walker Thomas , Quek Shannon , Jeffries Claire L. , Bandibabone Janvier , Dhokiya Vishaal , Bamou Roland , Kristan Mojca , Messenger Louisa A. , Gidley Alexandra , Hornett Emily A. , Anderson Enyia R. , Cansado-Utrilla Cintia , Hegde Shivanand , Bantuzeko Chimanuka , Stevenson Jennifer C. , Lobo Neil F. , Wagstaff Simon C. , Antonio Nkondjio Christophe , Heinz Eva , Hughes Grant L. 
Published: October 2020

AbstractWolbachia, a widespread bacterium that can reduce pathogen transmission in mosquitoes, has been detected within populations ofAnopheles (An.)malaria vectors. In theAn. gambiaecomplex, the primary vectors in Sub-Saharan Africa,Wolbachiastrains are at low density and infection frequencies in wild populations. PCR-independent evidence is required to determine whetherWolbachiastrains are true endosymbionts inAnophelesgiven most studies to date have used nested-PCR to identify strains. Here we report high-density strains found in geographically diverse populations ofAn. mouchetiandAn.demeilloni. Fluorescentin situhybridization localized a heavy infection in the ovaries ofAn. mouchetiand maternal transmission was observed. Genome sequencing of both strains obtained genome depths and coverages comparable to other known infections. Notably, homologs of cytoplasmic incompatibility factor (cif) genes were present indicating these strains possess the capacity to induce the phenotype cytoplasmic incompatibility which allowsWolbachiato spread through populations. The characteristics of these two strains suggest they are ideal candidates forWolbachiabiocontrol strategies inAnopheles.
Core Antibiotic-Induced Transcriptional Signatures Reflect Susceptibility to All Members of an Antibiotic Class
Authors: Martinsen Melanie A. , Cartagena Alexis Jaramillo , Bhattacharyya Roby P. 
Published: October 2020

AbstractCurrent growth-based antibiotic susceptibility testing (AST) is too slow to guide early therapy. We previously developed a diagnostic approach that quantifies antibiotic-induced transcriptional signatures to distinguish susceptible from resistant isolates, providing phenotypic AST 24-36h faster than current methods. Here, we show that 10 transcripts optimized for AST of one fluoroquinolone, aminoglycoside, or beta-lactam reflect susceptibility to other members of that class. This finding will streamline development and implementation of this strategy, facilitating efficient antibiotic deployment.
CK2 alpha prime and alpha-synuclein pathogenic functional interaction mediates synaptic dysregulation in Huntington’s disease
Authors: Yu Dahyun , Zarate Nicole , White Angel , Coates De’jah , Tsai Wei , Nanclares Carmen , Cuccu Francesco , Yue Johnny S. , Brown Taylor G. , Mansky Rachel , Jiang Kevin , Kim Hyuck , Nichols-Meade Tessa , Larson Sarah N. , Gundry Katie , Zhang Ying , Tomas-Zapico Cristina , Lucas Jose J. , Benneyworth Michael , Öz Gülin , Cvetanovic Marija , Araque Alfonso , Gomez-Pastor Rocio 
Published: October 2020

AbstractBackgroundHuntington’s Disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion inthe HTTgene for which no therapies are available. This mutation causes HTT protein misfolding and aggregation, preferentially affecting medium spiny neurons (MSNs) of the basal ganglia. Transcriptional perturbations in synaptic genes and neuroinflammation are key processes that precede MSN dysfunction and motor symptom onset. Understanding the interplay between these processes is crucial to develop effective therapeutic strategies to treat HD. We investigated whether protein kinase CK2α’, a kinase upregulated in MSNs in HD and previously associated with Parkinson’s disease (PD), participates in the regulation of neuroinflammation and synaptic function during HD progression.MethodsWe used the heterozygous knock-in zQ175 HD mouse model and compared that to zQ175 mice lacking one allele of CK2α’. We performed neuropathological analyses using immunohistochemistry, cytokine proteome profiling, RNA-seq analyses in the striatum, electrophysiological recordings, and behavioral analyses. We also used the murine immortalized striatal cell lines STHdhQ7and STHdhQ111and studied the expression of various synaptic genes dysregulated by CK2α’.ResultsWe showed that CK2α’ haploinsufficiency in zQ175 mice ameliorated neuroinflammation, HTT aggregation, transcriptional alterations, excitatory synaptic transmission, and motor coordination deficits. RNA-seq analyses also revealed a connection between α-syn, a protein associated with PD, and the transcriptional perturbations mediated by CK2α’ in HD. We also found increased α-syn serine 129 phosphorylation (pS129-α-syn), a post-translational modification linked to α-synucleinopathy, in the nuclei of MSNs in zQ175 mice and in patients with HD. Levels of pS129-α-syn were ameliorated in zQ175 lacking one allele of CK2α’.ConclusionsOur data demonstrated that CK2α’ contributes to transcriptional dysregulation of synaptic genes and neuroinflammation in zQ175 mice and its depletion improved several HD-like phenotypes in this mouse model. These effects were related to increased phosphorylation of S129-α-syn in the striatum of HD mice, suggesting that CK2α’ contributes to worsening HD by mediating synucleinopathy. Our study highlights a possible convergent mechanism of neurodegeneration between HD and PD and suggests targeting CK2α’ as a potential therapeutic strategy to ameliorate synaptic dysfunction in HD as well as other neurodegenerative diseases.
Evolution and adaptation ofPseudomonas aeruginosain the paranasal sinuses of people with cystic fibrosis
Authors: Armbruster Catherine R. , Marshall Christopher W. , Melvin Jeffrey A. , Zemke Anna C. , Garber Arkadiy I. , Moore John , Li Kelvin , Zamora Paula F. , Fritz Ian L. , Manko Christopher , Weaver Madison , Gaston Jordan , Morris Alison , Methé Barbara , Lee Stella E. , Cooper Vaughn S. , Bomberger Jennifer M. 
Published: October 2020

AbstractPeople with the genetic disorder cystic fibrosis (CF) harbor lifelong respiratory infections, with morbidity and mortality frequently linked to chronic lung infections dominated by the opportunistically pathogenic bacteriumPseudomonas aeruginosa. During chronic CF lung infections, a single clone ofP. aeruginosacan persist for decades and dominate end-stage CF lung disease due to its propensity to adaptively evolve to the respiratory environment, a process termed “pathoadaptation”. Chronic rhinosinusitis (CRS), chronic inflammation and infection of the sinonasal space, is highly prevalent in CF and the sinuses may serve as the first site in the respiratory tract to become colonized by bacteria that then proceed to seed lung infections. We identified three evolutionary genetic routes by whichP. aeruginosaevolves in the sinuses of people with CF, including through the evolution of mutator lineages and proliferative insertion sequences and culminating in early genomic signatures of host-restriction. Our findings raise the question of whether a significant portion of the pathoadaptive phenotypes previously thought to have evolved in response to selective pressures in the CF lungs may have first arisen in the sinuses and underscore the link between sinonasal and lung disease in CF.Graphical abstract and highlightsPseudomonas aeruginosaundergoes adaptive evolution in the sinuses of people with CFOver time, pathoadapted strains display early signatures of genome degradation consistent with recent host restrictionMutations previously thought to occur in CF lungs may have first evolved in sinuses
Novel enzyme for dimethyl sulfide-releasing in bacteria reveals a missing route in the marine sulfur cycle
Authors: Li Chun-Yang , Wang Xiu-Juan , Chen Xiu-Lan , Sheng Qi , Zhang Shan , Wang Peng , Quareshy Mussa , Rihtman Branko , Shao Xuan , Gao Chao , Li Fuchuan , Li Shengying , Chen Yin , Zhang Yu-Zhong 
Published: October 2020

AbstractDimethylsulfoniopropionate (DMSP) is an abundant and ubiquitous organosulfur molecule and plays important roles in the global sulfur cycle. Cleavage of DMSP produces volatile dimethyl sulfide (DMS), which has impacts on the global climate. Multiple pathways for DMSP catabolism have been identified. Here we identified yet another novel pathway, the ATP DMSP lysis pathway. The key enzyme, AcoD, is an ATP-dependent DMSP lyase. AcoD belongs to the acyl-CoA synthetase superfamily, which is totally different from other DMSP lyases, showing a new evolution route. AcoD catalyses the conversion of DMSP to DMS by a two-step reaction: the ligation of DMSP with CoA to form the intermediate DMSP-CoA, which is then cleaved to DMS and acryloyl-CoA. The novel catalytic mechanism was elucidated by structural and biochemical analyses. AcoD is widely distributed in many bacterial lineages including Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and Firmicutes, revealing this new pathway plays important roles in global DMSP/DMS cycles.
Pairwise genetic interactions modulate lipid plasma levels and cellular uptake
Authors: Zimon Magdalena , Huang Yunfeng , Trasta Anthi , Liu Jimmy Z. , Chen Chia-Yen , Halavatyi Aliaksandr , Blattmann Peter , Klaus Bernd , Whelan Christopher D. , Sexton David , John Sally , Huber Wolfgang , Tsai Ellen A. , Pepperkok Rainer , Runz Heiko 
Published: October 2020

SUMMARYGenetic interactions (GIs), the joint impact of different genes or variants on a phenotype, are foundational to the genetic architecture of complex traits. However, identifying GIs through human genetics is challenging since it necessitates very large population sizes, while findings from model systems not always translate to humans. Here, we combined exome-sequencing and genotyping in the UK Biobank with combinatorial RNA-interference (coRNAi) screening to systematically test for pairwise GIs between 30 lipid GWAS genes. Gene-based protein-truncating variant (PTV) burden analyses from 240,970 exomes revealed additive GIs forAPOBwithPCSK9andLPL, respectively. Both, genetics and coRNAi identified additive GIs for 12 additional gene pairs. Overlapping non-additive GIs were detected only forTOMM40at theAPOElocus withSORT1andNCAN. Our study identifies distinct gene pairs that modulate both, plasma and cellular lipid levels via additive and non-additive effects and nominates drug target pairs for improved lipid-lowering combination therapies.
Rab34 GTPase mediates ciliary membrane biogenesis in the intracellular ciliogenesis pathway
Authors: Ganga Anil Kumar , Kennedy Margaret C. , Oguchi Mai E. , Gray Shawn D. , Oliver Kendall E. , Knight Tracy A. , De La Cruz Enrique M. , Homma Yuta , Fukuda Mitsunori , Breslow David K. 
Published: October 2020

AbstractPrimary cilia form by two pathways: an extracellular pathway in which the cilium grows out from the cell surface and an intracellular pathway in which the nascent cilium forms inside the cell. Here we identify the GTPase Rab34 as a selective mediator of intracellular ciliogenesis. We find that Rab34 is required for formation of the ciliary vesicle at the mother centriole and that Rab34 marks the ciliary sheath, a unique sub-domain of assembling intracellular cilia. Rab34 activity is modulated by divergent residues within its GTPase domain, and ciliogenesis requires GTP binding and turnover by Rab34. Because Rab34 is found on assembly intermediates that are unique to intracellular ciliogenesis, we tested its role in the extracellular pathway used by MDCK cells. Consistent with Rab34 acting specifically in the intracellular pathway, MDCK cells ciliate independently of Rab34 and paralog Rab36. Together, these findings reveal a new context-specific molecular requirement for ciliary membrane biogenesis.