bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood conduct problems are associated with reduced white matter fibre density and morphology
Authors: Burley Daniel T. , Genc Sila , Silk Timothy J. 
Published: May 2020

AbstractChildhood conduct problems are an important public health issue as these children are at-risk of adverse outcomes. Studies using diffusion Magnetic Resonance Imaging (dMRI) have found that conduct problems in adults are characterised by abnormal white-matter microstructure within a range of white matter pathways underpinning socio-emotional processing, while evidence within children and adolescents has been less conclusive based on non-specific diffusion tensor imaging metrics. Fixel-based analysis (FBA) provides measures of fibre density and morphology that are more sensitive to developmental changes in white matter microstructure. The current study used FBA to investigate whether childhood conduct problems were related both cross-sectionally and longitudinally to microstructural alterations within the fornix, inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and the uncinate fasciculus (UF). dMRI data was obtained for 130 children across two time-points in a community sample with high levels of externalising difficulties (age: time-point 1 = 9.47 – 11.86 years, time-point 2 = 10.67 −13.45 years). Conduct problems were indexed at each time-point using the Conduct Problems subscale of the parent-informant Strengths and Difficulties Questionnaire (SDQ). Conduct problems were related to lower fibre density in the fornix at both time-points, and in the ILF at time-point 2. We also observed lower fibre cross-section in the UF at time-point 1. The change in conduct problems did not predict longitudinal changes in white-matter microstructure across time-points. The current study suggests that childhood conduct problems are related to reduced fibre-specific microstructure within white matter fibre pathways implicated in socio-emotional functioning.
Unique retinal binding pocket of primate blue-sensitive visual pigment
Authors: Nonaka Yuki , Hanai Shunpei , Katayama Kota , Imai Hiroo , Kandori Hideki 
Published: May 2020

ABSTRACTThe visual pigments of humans contain 11-cisretinal as the chromophore of light perception, and its photoisomerization to the all-transform initiates visual excitation in our eyes. It is well known that three isomeric states of retinal (11-cis, all-trans, and 9-cis) are in photoequilibrium at very low temperatures such as 77 K. Here we report the lack of formation of the 9-cisform in monkey blue (MB) at 77 K, as revealed by light-induced difference FTIR spectroscopy. This indicates that the chromophore binding pocket of MB does not accommodate the 9-cisform, even though it accommodates the all-transform by twisting the chromophore. Mutation of the blue-specific tyrosine at position 265 into tryptophan, which is highly conserved in other animal rhodopsins, led to formation of the 9-cisform in MB, suggesting that Y265 is one of the determinants of the unique photochemistry in blue pigments. We also found that 9-cisretinal does not bind to MB opsin, implying that the chromophore binding pocket does not accommodate the 9-cisform at physiological temperature. The unique property of MB is discussed based on the present results.
Validation of a smartphone embedded inertial measurement unit for measuring postural stability in older adults
Authors: De Groote Friedl , Vandevyvere Stefanie , Vanhevel Florian , Orban de Xivry Jean-Jacques 
Published: May 2020

AbstractBackgroundIdentifying older adults with increased fall risk due to poor postural control on a large scale is only possible through omnipresent and low cost measuring devices such as the inertial measurement units (IMU) embedded in smartphones. However, the correlation between smartphone measures of postural stability and state-of-the-art force plate measures has never been assessed in a large sample allowing us to take into account age as a covariate.Research questionHow reliably can postural stability be measured with a smartphone embedded IMU in comparison to a force plate?MethodsWe assessed balance in 97 adults aged 50 to 90 years in four different conditions (eyes open, eyes closed, semi-tandem and dual-task) in the anterio-posterior and medio-lateral directions. We used six different parameters (root mean square and average absolute value of COP displacement, velocity and acceleration) for the force plate and two different parameters (root mean square and average absolute value of COM acceleration) for the smartphone.ResultsTest-retest reliability was smaller for the smartphone than for the force plate (intra class correlation) but both devices could equally well detect differences between conditions (similar Cohen’s d). Parameters from the smartphone and the force plate, with age regressed out, were moderately correlated (robust correlation coefficients of around 0.5).SignificanceThis study comprehensively documents test-retest reliability and effect sizes for stability measures obtained with a force plate and smartphone as well as correlations between force plate and smartphone measures based on a large sample of older adults. Our large sample size allowed us to reliably determine the strength of the correlations between force plate and smartphone measures. The most important practical implication of our results is that more repetitions or longer trials are required when using a smartphone instead of a force plate to assess balance.HighlightsWe compared balance measures simultaneously obtained from a phone and a force plateFor precision purposes, we included a large group of older participants (N=97).Using age as covariate, we found a moderate correlation across the two devices.Intra-class correlation coefficients were smaller for the smartphone.Balance assessment with smartphones requires longer trials compared to force plates.
Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by mutation of the psychiatric risk geneCacna1c
Authors: Tigaret Cezar M. , Lin Tzu-Ching E. , Morrell Edward , Sykes Lucy , O’Donovan Michael C. , Owen Michael J. , Wilkinson Lawrence S. , Jones Matthew W. , Thomas Kerrie L. , Hall Jeremy 
Published: May 2020

AbstractGenetic variation inCACNA1C, which encodes the alpha-1 subunit of CaV1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. To translate genetics to neurobiological mechanisms and rational therapeutic targets, we investigated the impact of alteredCacna1cdosage on rat cognitive, synaptic and circuit phenotypes implicated by patient studies. We show that rats hemizygous forCacna1charbor marked impairments in learning to disregard non-salient stimuli, a behavioral change previously associated with psychosis. This behavioral deficit is accompanied by dys-coordinated network oscillations during learning, pathway-selective disruption of hippocampal synaptic plasticity, attenuated Ca2+signaling in dendritic spines and decreased signaling through the Extracellular-signal Regulated Kinase (ERK) pathway. Activation of the ERK pathway by a small molecule agonist of TrkB/TrkC neurotrophin receptors rescued both behavioral and synaptic plasticity deficits inCacna1c+/-rats. These results map a route through which genetic variation inCACNA1Ccan disrupt experience-dependent synaptic signaling and circuit activity, culminating in cognitive alterations associated with psychiatric disorders. Our findings highlight targeted activation of neurotrophin signaling pathways with BDNF mimetic drugs as a novel, genetically informed therapeutic approach for rescuing behavioral abnormalities in psychiatric disorder.One Sentence SummaryNeurotrophin receptor activation reveals that BDNF mimetic drugs have therapeutic potential to ameliorate genetic risk for psychiatric disorders.
Quantitative live-cell PALM reveals nanoscopic Faa4 redistributions and dynamics on lipid droplets during metabolic transitions of yeast
Authors: Adhikari Santosh , Moscatelli Joe , Puchner Elias M. 
Published: May 2020

AbstractLipid droplets (LDs) are dynamic lipid storage organelles needed for lipid homeostasis. Cells respond to metabolic changes by regulating the spatial distribution of LDs, as well as enzymes required for LD growth and turnover. Due to LD size below the optical diffraction limit, bulk fluorescence microscopy cannot observe the density and dynamics of specific LD enzymes. Here, we employ quantitative photo-activated localization microscopy (PALM) to study the density of the fatty acid activating protein Faa4 on LDs during log, stationary and lag phases in live yeast cells with single-molecule sensitivity and 30 nm resolution. During the log phase LDs co-localize with the Endoplasmic Reticulum (ER) where the highest Faa4 densities are measured. During transition to the stationary phase LDs translocate to the vacuolar surface and lumen with a ~2-fold increased surface area and a ~2.5-fold increase in Faa4 density, suggesting its role in LD expansion. The increased Faa4 density on LDs is caused by its ~5-fold increased expression level. When lipolysis is induced in stationary-phase cells by diluting them for 2 hrs in fresh medium, Faa4 shuttles to the vacuole through the two observed routes of ER- and lipophagy. The observed vacuolar localization of Faa4 may help activating fatty acids for membrane expansion and reduces Faa4 expression to levels found in the log phase.
Obesity phenotypes are preserved in intestinal stem cell enteroids from morbidly obese patients
Authors: Hasan Nesrin M. , Johnson Kelli F. , Yin Jianyi , Baetz Nicholas W. , Sherman Vadim , Blutt Sarah E. , Estes Mary K. , Kumbhari Vivek , Zachos Nicholas C. , Kovbasnjuk Olga 
Published: May 2020

AbstractObesity and obesity-related comorbidities are significant health care challenges. Bariatric surgery (BS) is the most effective therapy for treating obesity and type 2 diabetes. A barrier in the development of therapeutic alternatives is incomplete mechanistic understanding of the benefits of BS and the lack of human intestinal models that recapitulate the pathophysiology of obesity. Using adult intestinal stem cell-derived enteroid cultures established from healthy lean subjects and morbidly obese patients, including post-BS cases, four phenotypes correlating patient BMI and intestinal glucose absorption were identified suggesting that enteroids retain patient phenotype heterogeneity associated with healthy and diseased state. In a sub-population of obese patients, increased dietary glucose absorption and gluconeogenesis was due to significantly higher expression of intestinal carbohydrate transporters (SGLT1, GLUT2 and GLUT5) and gluconeogenic enzymes (PEPCK1 and G6Pase) compared to enteroids from lean subjects that demonstrated low glucose absorption and lacked gluconeogenesis. Enteroids established from successful BS cases exhibited low glucose absorption similar to that observed in lean subjects. These data show that human enteroids preserve the patient phenotype in long-term cultures and represent a reliable preclinical model to study the heterogeneity of the obesity mechanisms, which is necessary to determine the efficacy of therapeutic interventions.
Investigations of dimethylglycine (DMG), glycine betaine and ectoine uptake by a BCCT family transporter with broad substrate specificity inVibriospecies
Authors: Gregory Gwendolyn J. , Dutta Anirudha , Parashar Vijay , Boyd E. Fidelma 
Published: May 2020

AbstractFluctuations in osmolarity are one of the most prevalent stresses to which bacteria must adapt, both hypo- and hyper-osmotic conditions. Most bacteria cope with high osmolarity by accumulating compatible solutes (osmolytes) in the cytoplasm to maintain the turgor pressure of the cell.Vibrio parahaemolyticus, a halophile, utilizes at least six compatible solute transporters for the uptake of osmolytes: two ABC family ProU transporters and four betaine-carnitine-choline transporter (BCCT) family transporters. The full range of compatible solutes transported by this species has yet to be determined. Using an osmolyte phenotypic microarray plate for growth analyses, we expanded known osmolytes used byV. parahaemolyticusto include N-N dimethylglycine (DMG) amongst others. We showed thatV. parahaemolyticusrequires a BCCT transporter for DMG uptake, carriers that were not known to transport DMG. Growth pattern analysis of four triple-bccTmutants, possessing only one functional BCCT, indicated that BccT1 (VP1456), BccT2 (VP1723), and BccT3 (VP1905) transported DMG, which was confirmed by functional complementation inE. colistrain MKH13. BccT1 was unusual in that it could uptake both compounds with methylated head groups (glycine betaine (GB), choline and DMG) and cyclic compounds (ectoine and proline). Bioinformatics analysis identified the four coordinating residues for glycine betaine in BccT1.In silicomodelling analysis demonstrated that glycine betaine, DMG, and ectoine docked in the same binding pocket in BccT1. Using site-directed mutagenesis, we showed that a strain with all four resides mutated resulted in loss of uptake of glycine betaine, DMG and ectoine. We showed three of the four residues were essential for ectoine uptake whereas only one of the residues was essential for glycine betaine uptake. Overall, we have demonstrated that DMG is a highly effective compatible solute forVibriospecies and have elucidated the amino acid residues in BccT1 that are important for coordination of glycine betaine, DMG and ectoine transport.ImportanceVibrio parahaemolyticuspossesses at least six osmolyte transporters, which allow the bacterium to adapt to high salinity conditions. In this study, we identified several novel osmolytes that are utilized byV. parahaemolyticus. We demonstrated that the compound dimethylglycine (DMG), which is abundant in the marine environment, is a highly effective osmolyte forVibriospecies. We determined that DMG is transported via BCCT-family carriers, which have not been shown previously to uptake this compound. BccT1 was a carrier for glycine betaine, DMG and ectoine and we identified the amino acid residues essential for coordination of these compounds. The data suggest that for BccT1, glycine betaine is more easily accommodated than ectoine in the transporter binding pocket.
animalcules: Interactive Microbiome Analytics and Visualization in R
Authors: Zhao Yue , Federico Anthony , Faits Tyler , Manimaran Solaiappan , Monti Stefano , Johnson W. Evan 
Published: May 2020

AbstractBackgroundMicrobial communities that live in and on the human body play a vital role in health and disease. Recent advances in sequencing technologies have enabled the study of microbial communities at unprecedented resolution. However, these advances in data generation have presented novel challenges to researchers attempting to analyze and visualize these data.ResultsTo address some of these challenges, we have developedanimalcules, an easy-to-use interactive microbiome analysis toolkit for 16S rRNA sequencing data, shotgun DNA metagenomics data, and RNA-based metatranscriptomics profiling data. This toolkit combines novel and existing analytics, visualization methods, and machine learning models. For example, traditional microbiome analyses such as alpha/beta diversity and differential abundance analysis are enhanced in the toolkit, while new methods such as biomarker identification are introduced. Powerful interactive and dynamic figures generated byanimalculesenable users to understand their data and discover new insights.animalculescan be used as a standalone command-line R package or users can explore their data with the accompanying interactive R Shiny interface.ConclusionsWe presentanimalcules, an R package for interactive microbiome analysis through either an interactive interface facilitated by R Shiny or various command-line functions. It is the first microbiome analysis toolkit that supports the analysis of all 16S rRNA, DNA-based shotgun metagenomics, and RNA-sequencing based metatranscriptomics datasets.animalculescan be freely downloaded from GitHub athttps://github.com/compbiomed/animalculesor installed through Bioconductor athttps://www.bioconductor.org/packages/release/bioc/html/animalcules.html.
CryoEM map ofPseudomonas aeruginosaPilQ enables structural characterization of TsaP
Authors: McCallum Matthew , Tammam Stephanie , Rubinstein John L. , Burrows Lori L. , Howell P. Lynne 
Published: May 2020

ABSTRACTThe type IV pilus machinery is a multi-protein complex that polymerizes and depolymerizes a pilus fibre used for attachment, twitching motility, phage adsorption, natural competence, protein secretion, and surface-sensing. An outer membrane secretin pore is required for passage of the pilus fibre out of the cell. Herein, the structure of the tetradecameric secretin, PilQ, from thePseudomonas aeruginosatype IVa pilus system was determined to 4.3 Å and 4.4 Å resolution in the presence and absence of C7symmetric spokes, respectively. The heptameric spokes were found to be the two tandem C-terminal domains of TsaP. TsaP forms a belt around PilQ and while the protein is not essential for twitching motility, over-expression of TsaP triggers a signal cascade upstream of PilY1 leading to cyclic di-GMP up-regulation. These results resolve the identity of the spokes identified with Proteobacterial PilQ homologs and may reveal a new component of the surface-sensing cyclic di-GMP signal cascade.IMPACT STATEMENTThe type IV pilus is critical for bacterial virulence. The co-structure of the pilus secretin PilQ and TsaP is determined. Characterization of TsaP implicates it in surface-sensing signal transduction.
Coordinated evolution between N2 neuraminidase and H1 and H3 hemagglutinin genes increased influenza A virus genetic diversity in swine
Authors: Zeller Michael A. , Chang Jennifer , Vincent Amy L. , Gauger Phillip C. , Anderson Tavis K. 
Published: May 2020

AbstractThe neuraminidase (NA) and hemagglutinin (HA) of influenza A virus (IAV) are essential surface glycoproteins. In this study, the evolution of subtype N2 NA paired with H1 and H3 subtype HA in swine was evaluated to understand if genetic diversity of HA and NA were linked. Using time-scaled Bayesian phylodynamic analyses, the relationships of paired swine N2 with H1 or H3 from 2009 to 2018 were evaluated. These data demonstrated increased relative genetic diversity within the major N2 clades circulating in swine (N2.1998 between 2014-2017 and N2.2002 between 2010-2016). Relative genetic diversity of NA-HA pairs (e.g., N2.1998B/ H1.Delta1B) were correlated, suggesting intergene epistasis. Preferential pairing was observed among specific NA and HA genetic clades and this was associated with gene reassortment between cocirculating influenza A strains. Using the phylogenetic topology of inferred N2 trees, the expansion of genetic diversity in the NA gene was quantified and increases in diversity were observed subsequent to NA-HA reassortment events. The rate of evolution among NA-N2 clades and HA-H1 and HA-H3 clades were similar. The frequent regional movement of pigs and their influenza viruses is a possible explanation driving this pattern of drift, reassortment, and rapid evolution. Bayesian phylodynamic analyses demonstrated strong spatial patterns in N2 genetic diversity, and that frequent interstate movement of N2 clades homogenized diversity. The reassortment and evolution of NA and its influence on HA evolution may affect antigenic drift, impacting vaccine control programs and animal health.
Dynamic cerebellar network organization across the human menstrual cycle
Authors: Fitzgerald Morgan , Pritschet Laura , Santander Tyler , Grafton Scott T. , Jacobs Emily G. 
Published: May 2020

AbstractThe cerebellum contains the vast majority of neurons in the brain and houses distinct functional networks that constitute at least two homotopic maps of the cerebrum. While the functional organization of the human cerebellum has been characterized, the influence of sex steroid hormones on intrinsic cerebellar network dynamics has yet to be established. Here, we investigated the extent to which endogenous fluctuations in estradiol and progesterone alter functional cerebellar networks at rest in a woman densely sampled over a complete menstrual cycle (30 consecutive days). Edgewise regression analysis revealed negative associations between sex hormones and cerebellar coherence, with progesterone showing more pronounced negative associations relative to estradiol. Graph theory metrics probed sex hormones’ influence on topological brain states, revealing relationships between sex hormones and intra- and inter-network integration in Ventral Attention, Dorsal Attention, and Somato-Motor Networks. Together, these results suggest that the intrinsic dynamics of the cerebellum are intimately tied to day-by-day changes in sex hormones.
Reduced Gene Dosage of Histone H4 Prevents CENP-A Mislocalization inSaccharomyces cerevisiae
Authors: Eisenstatt Jessica R. , Ohkuni Kentaro , Au Wei-Chun , Preston Olivia , Suva Evelyn , Costanzo Michael , Boone Charles , Basrai Munira A. 
Published: May 2020

ABSTRACTMislocalization of the centromeric histone H3 variant (Cse4 in budding yeast, CID in flies, CENP-A in humans) to non-centromeric regions contributes to chromosomal instability (CIN) in yeast, fly, and human cells. Overexpression and mislocalization of CENP-A has been observed in cancers, however, the mechanisms that facilitate the mislocalization of overexpressed CENP-A have not been fully explored. Defects in ubiquitin-mediated proteolysis of overexpressed Cse4 (GALCSE4) leads to its mislocalization and synthetic dosage lethality (SDL) in mutants for E3 ubiquitin ligases (Psh1, Slx5, SCFMet30, SCFCdc4), Doa1, Hir2, and Cdc7. In contrast, defects in sumoylation ofGALcse4K215/216/A/Rprevent its mislocalization and do not cause SDL in apsh1Δ strain. Here, we used a genome-wide screen to identify factors that facilitate the mislocalization of overexpressed Cse4 by characterizing suppressors of thepsh1ΔGALCSE4SDL. Deletions of histone H4 alleles (HHF1orHHF2), which were among the most prominent suppressors, also suppressslx5Δ, cdc4-1, doa1Δ, hir2Δ, andcdc7-4 GALCSE4SDL. Reduced dosage ofH4contributes to defects in sumoylation and reduced mislocalization of overexpressed Cse4. We determined that thehhf1-20, cse4-102, andcse4-111mutants, which are defective in the Cse4-H4 interaction, also exhibit reduced sumoylation of Cse4 and do not displaypsh1ΔGALCSE4SDL. In summary, we have identified genes that contribute to the mislocalization of overexpressed Cse4 and defined a role for the gene dosage ofH4in facilitating Cse4 sumoylation and mislocalization to non-centromeric regions, contributing to SDL when Cse4 is overexpressed in mutant strains.