bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures
Authors: Brahmachari Sumitabha , Marko John F. 
Published: April 2019

AbstractEukaryote cell division features a chromosome compaction-decompaction cycle that is synchronized with their physical and topological segregation. It has been proposed that lengthwise compaction of chromatin into mitotic chromosomes via loop extrusion underlies the compaction-segregation/resolution process. We analyze this disentanglement scheme via considering the chromosome to be a succession of DNA/chromatin loops - a polymer “brush” - where active extrusion of loops controls the brush structure. Given topoisomerase (TopoII)-catalyzed topology fluctuations, we find that inter-chromosome entanglements are minimized for a certain “optimal” loop that scales with the chromosome size. The optimal loop organization is in accord with experimental data across species, suggesting an important structural role of genomic loops in maintaining a less entangled genome. Application of the model to the interphase genome indicates that active loop extrusion can maintain a level of chromosome compaction with suppressed entanglements; the transition to the metaphase state requires higher lengthwise compaction, and drives complete topological segregation. Optimized genomic loops may provide a means for evolutionary propagation of gene-expression patterns while simultaneously maintaining a disentangled genome. We also find that compact metaphase chromosomes have a densely packed core along their cylindrical axes that explains their observed mechanical stiffness. Our model connects chromosome structural reorganization to topological resolution through the cell cycle, and highlights a mechanism of directing Topo-II mediated strand passage via loop extrusion driven lengthwise compaction.
Unraveling the relation between EEG-correlates of attentional orienting and sound localization performance: a diffusion model approach
Authors: Klatt Laura-Isabelle , Schneider Daniel , Schubert Anna-Lena , Hanenberg Christina , Lewald Jörg , Wascher Edmund , Getzmann Stephan 
Published: April 2019

AbstractUnderstanding the contribution of cognitive processes and their underlying neurophysiological signals to behavioral phenomena has been a key objective in recent neuroscience research. Using a diffusion-model framework, we investigated to what extent well-established correlates of spatial attention in the electro-encephalogram contribute to behavioral performance in an auditory free-field sound-localization task. Younger and older participants were instructed to indicate the horizontal position of a pre-defined target among three simultaneously presented distractors. The central question of interest was whether posterior alpha lateralization and amplitudes of the anterior contralateral N2 subcomponent (N2ac) predict sound localization performance (accuracy, mean reaction time) and/or diffusion model parameters (drift rate, boundary separation, non-decision time). Two age groups were compared to explore whether in older adults, who struggle with multi-speaker environments, the brain-behavior relationship would differ from younger adults. Regression analyses revealed that N2ac amplitudes predicted drift rate and accuracy, whereas alpha lateralization was not related to behavioral or diffusion modeling parameters. This was true irrespective of age. The results indicate that a more efficient attentional filtering and selection of information within an auditory scene, reflected by increased N2ac amplitudes, was associated with a higher speed of information uptake (drift rate) and better localization performance (accuracy), while the underlying response criteria (threshold separation), mean reaction times, and non-decisional processes remained unaffected. The lack of a behavioral correlate of post-stimulus alpha power lateralization constrast the well-established notion that pre-stimulus alpha power reflects a functionally relevant attentional mechanism. This highlights the importance of distinguishing anticipatory from post-stimulus alpha power modulations.
Epidemic Growth Rates and Host Movement Patterns Shape Management Performance for Pathogen Spillover at The Wildlife-livestock Interface
Authors: Manlove Kezia R. , Sampson Laura M. , Borremans Benny , Cassirer E. Frances , Miller Ryan S. , Pepin Kim M. , Besser Thomas E. , Cross Paul C. 
Published: April 2019

ABSTRACTManaging pathogen spillover at the wildlife-livestock interface is a key step toward improving global animal health, food security, and wildlife conservation. However, predicting the effectiveness of management actions across host-pathogen systems with different life histories is an on-going challenge since data on intervention effectiveness are expensive to collect and results are system-specific. We developed a simulation model to explore how the efficacies of different management strategies vary according to host movement patterns and epidemic growth rates. The model suggested that fast-growing, fast-moving epidemics like avian influenza were best-managed with actions like biosecurity or containment, which limited and localized overall spillover risk. For fast-growing, slower-moving diseases like foot-and-mouth disease, depopulation or prophylactic vaccination were competitive management options. Many actions performed competitively when epidemics grew slowly and host movements were limited, and how management efficacy related to epidemic growth rate or host movement propensity depended on what objective was used to evaluate management performance. This framework may be a useful step in advancing how we classify and prioritise responses to novel pathogen spillover threats, and evaluate current management actions for pathogens emerging at the wildlife-livestock interface.
Relationship between gut microbiota and circulating metabolites in population-based cohorts
Authors: Vojinovic Dina , Radjabzadeh Djawad , Kurilshikov Alexander , Amin Najaf , Wijmenga Cisca , Franke Lude , Ikram M. Arfan , Uitterlinden Andre G. , Zhernakova Alexandra , Fu Jingyaun , Kraaij Robert , van Duijn Cornelia M. 
Published: April 2019

ABSTRACTGut microbiota has been implicated in major diseases affecting the human population and has also been linked to triglycerides and high-density lipoprotein levels in the circulation. As recent development in metabolomics allows classifying the lipoprotein particles into more details, we aimed to examine the impact of gut microbiota on circulating metabolites measured by Nuclear Magnetic Resonance (1H-NMR) technology in 2,309 individuals from the Rotterdam Study and the LifeLines-DEEP cohort in whom gut microbiota was profiled using 16S rRNA gene sequencing. The relationship between gut microbiota and metabolites was assessed by linear regression analysis while adjusting for age, sex, body-mass index, technical covariates, medication use, and multiple testing. Our analysis revealed association of 32 microbial families and genera with very-low-density and high-density subfractions, serum lipid measures, glycolysis-related metabolites, amino acids, and acute phase reaction markers. These observations provide novel insights into the role of microbiota in host metabolism and support the potential of gut microbiota as a target for therapeutic and preventive interventions.
Workplace Harassment and Risk of Depression Among Adults in the United States
Authors: Aduse-Poku Livingstone , Jahanfar Shayester 
Published: April 2019

AbstractPurposeThe purpose of the study is to perform an analysis of the relationship between workplace harassment and risk depression among adults in the United States.MethodsAcross-sectional study of 33772 adults was done using the National Health Interview Survey (NHIS) sample adult data in the USA. The variables collected included depression, harassment, age, race, sex, and marital status. Data was analyzed using IBM Statistical Package for the Social Sciences (SPSS) for windows, version 25.0.ResultsResults showed a possible relationship between workplace harassment and depression among adults. Adults who were harassed were 0.39 times more likely to be depressed than those who were not harassed (95%CI: 0.45-0.81), after adjusting for sex, age, race, marital status, pay, and number of years on the job, the odd was almost the same [AOR (95%CI):0.55(0.40-0.77)].ConclusionThe findings of the study show that there is a positive association between workplace harassment and depression.
Polyglutamine-expanded androgen receptor disrupts muscle triad, calcium dynamics and the excitation-contraction coupling gene expression program
Authors: Chivet M , Marchioretti C , Pirazzini M , Piol D , Scaramuzzino C , Polanco JM , Nath S , Zuccaro E , Nogara L , Canato M , Marcucci L , Parodi S , Romanello V , Armani A , D’Antonio M , Sambataro F , Dassi E , Pegoraro E , Sorarù G , Rinaldi C , Lieberman AP , Blaauw B , Sandri M , Basso M , Pennuto M 
Published: April 2019

AbstractSpinal and bulbar muscular atrophy (SBMA) is caused by polyglutamine (polyQ) expansions in the androgen receptor (AR) gene. Although clinical and experimental evidence highlight a primary role for skeletal muscle in the onset, progression, and outcome of disease, the pathophysiological and molecular processes underlying SBMA muscle atrophy are poorly understood. Here we show that polyQ-expanded AR alters intrinsic muscle force generation before denervation. Reduced muscle force was associated with a switch in fiber-type composition, disrupted muscle striation, altered calcium (Ca++) dynamics in response to muscle contraction, and aberrant expression of excitation-contraction coupling (ECC) machinery genes in transgenic, knock-in and inducible SBMA mice and patients. Importantly, treatment to suppress polyQ-expanded AR toxicity restored ECC gene expression back to normal. Suppression of AR activation by surgical castration elicited similar ECC gene expression changes in normal mice, suggesting that AR regulates the expression of these genes in physiological conditions. Bioinformatic analysis revealed the presence of androgen-responsive elements on several genes involved in muscle function and homeostasis, and experimental evidence showed AR-dependent regulation of expression and promoter occupancy of the most up-regulated gene from transcriptomic analysis in SBMA muscle, i.e. sarcolipin, a key ECC gene. These observations reveal an unpredicted role for AR in the regulation of expression of genes involved in muscle contraction and Ca++ dynamics, a level of muscle function regulation that is disrupted in SBMA muscle, yet restored by pharmacologic treatment.
Retromer repletion with AAV9-VPS35 restores endosomal function in the mouse hippocampus
Authors: Qureshi Yasir H. , Berman Diego E. , Klein Ronald L. , Patel Vivek M. , Simoes Sabrina , Kannan Suvarnambiga , Cox Rebecca , Waksal Samuel D , Stevens Beth , Petsko Gregory A. , Small Scott A. 
Published: April 2019

ABSTRACTRetromer has emerged as a master conductor of endosomal trafficking, and VPS35 and other retromer-related proteins are found to be deficient in late-onset Alzheimer’s disease (AD). Depleting VPS35 in neurons impairs retromer function, affecting for example the trafficking of the amyloid-precursor protein (APP) and the glutamate receptor GluA1. Whether VPS35 repletion, after chronic in vivo depletion, can rescue these impairments remains unknown. Here we set out to address this question by using a viral vector approach for VPS35 repletion. First, we completed a series of studies using neuronal cultures in order to optimize AAV9-VPS35 delivery, and to understand how exogenous VPS35 expression affects its endogenous levels as well as its binding to other retromer proteins. Next, we completed a series of studies in wildtype mice to determine the optimum protocol for in vivo delivery of AAV9-VPS35 to the hippocampus. We relied on this information to deliver AAV9-VPS35 to the hippocampus of mice genetically engineered to have chronic, neuronal-selective, VPS35 depletion. VPS35 repletion in the hippocampus was found to normalize APP cleavage and to restore glutamate receptor levels. Unexpectedly, chronic VPS35 depletion in neurons caused glial activation, similar to the pattern observed in AD, which was also partially normalized by VPS35 repletion. Taken together, these studies strengthen the mechanistic link between retromer and AD, and have therapeutic implications.
Serotonergic modulation of visual neurons inDrosophila melanogaster
Authors: Sampson Maureen M , Myers Gschweng Katherine M , Hardcastle Ben J , Bonanno Shivan L , Sizemore Tyler R , Arnold Rebecca C , Gao Fuying , Dacks Andrew M , Frye Mark A , Krantz David E 
Published: April 2019

AbstractSensory systems rely on neuromodulators, such as serotonin, to provide flexibility for information processing in the face of a highly variable stimulus space. Serotonergic neurons broadly innervate the optic ganglia ofDrosophila melanogaster, a widely used model for studying vision. The role for serotonergic signaling in theDrosophilaoptic lobe and the mechanisms by which serotonin regulates visual neurons remain unclear. Here we map the expression patterns of serotonin receptors in the visual system, focusing on a subset of cells with processes in the first optic ganglion, the lamina, and show that serotonin can modulate visual responses. Serotonin receptors are expressed in several types of columnar cells in the lamina including 5-HT2B in lamina monopolar cell L2, required for the initial steps of visual processing, and both 5-HT1A and 5-HT1B in T1 cells, whose function is unknown. Subcellular mapping with GFP-tagged 5-HT2B and 5-HT1A constructs indicates that these receptors localize to layer M2 of the medulla, proximal to serotonergic boutons, suggesting that the medulla is the primary site of serotonergic regulation for these neurons. Serotonin increases intracellular calcium in L2 terminals in layer M2 and alters the kinetics of visually induced calcium transients in L2 neurons following dark flashes. These effects were not observed in flies without a functional 5-HT2B, which displayed severe differences in the amplitude and kinetics of their calcium response to both dark and light flashes. While we did not detect serotonin receptor expression in L1 neurons, they also undergo serotonin-induced calcium changes, presumably via cell non-autonomous signaling pathways. We provide the first functional data showing a role for serotonergic neuromodulation of neurons required for initiating visual processing inDrosophilaand establish a new platform for investigating the serotonergic neuromodulation of sensory networks.Author SummarySerotonergic neurons innervate theDrosophila melanogastereye, but the function of serotonergic signaling is not known. We found that serotonin receptors are expressed in all neuropils of the optic lobe and identify specific neurons involved in visual information processing that express serotonin receptors. We then demonstrate that activation of these receptors can alter how visual information is processed. These are the first data suggesting a functional role for serotonergic signaling inDrosophilavision. This study contributes to the understanding of serotonin biology and modulation of sensory circuits.
Effect of mannose modified chitosan on uptake of nanoparticles by macrophages
Authors: Lowsberg David , Smith John 
Published: April 2019

AbstractThis report provided a new method to prepare and evaluate mannose-modified chitosan-coated lactic acid-glycolic acid copolymer (PLGA) nanoparticles, and to investigate their effects on macrophage toxicity and macrophage uptake. The PLGA nanoparticles loaded with ovalbumin (OVA) were prepared by double emulsion method. The size and zeta potential of the nanoparticles were determined by laser granulometry after mannose-modified chitosan coating. The nanoparticles were observed by transmission electron microscopy. The appearance of the form, the BCA method to determine the OVA content, calculate the drug loading and release. The OVA nanoparticles labeled with fluorescein isothiocyanate (FITC) were co-incubated with macrophages (RAW 264. 7), cell viability was determined by MTT assay, and uptake was examined by fluorescence microscopy. Results The size and ζ potential of OVA-PLGA nanoparticles increased with the increase of chitosan coating concentration (P < 0.05), and OVA drug loading range was 7. 2% to 8. 4%. Chitosan and mannose modified chitosan coating FITC-OVAPLGA nanoparticles and RAW 264. 7 After incubation, there was little effect on cell viability (P > 0.05), but it significantly promoted macrophage uptake by FITC-OVA-PLGA nanoparticles (P < 0.05).
Signaling via GABAB receptors regulates early development and neurogenesis in the basal metazoan Nematostella vectensis
Authors: Levy Shani , Brekhman Vera , Bakhman Anna , Sebé-Pedrós Arnau , Kosloff Mickey , Lotan Tamar 
Published: April 2019

AbstractThe metabotropic gamma-amino-butyric acid B receptor (GABABR) is a G protein–coupled receptor that mediates neuronal inhibition by the neurotransmitter GABA. Here, we identified putative GABAB receptors and signaling modulators in the basal sea anemone Nematostella vectensis. Activation of GABABR signaling reversibly arrests planula-to-polyp transformation during early development and affects the neurogenic program. We identified four Nematostella GABABR homologs that have the conserved 3D extracellular domains and residues needed for binding of GABA and the GABABR agonist baclofen. Transcriptomic analysis, combined with spatial analysis of baclofen-treated planulae, revealed that baclofen down-regulated pro-neural factors such as NvSoxB(2), NvNeuroD1 and NvElav1. Baclofen also inhibited neuron development and extended neurites, resulting in an under-developed and less organized nervous system. Our results shed light on cnidarian development and suggest an evolutionarily conserved function for GABABR in regulation of neurogenesis, highlighting Nematostella as a new model system to study GABABR signaling.
The bumble bee microbiome increases survival of bees exposed to selenate toxicity
Authors: Rothman Jason A. , Leger Laura , Graystock Peter , Russell Kaleigh , McFrederick Quinn S. 
Published: April 2019

SummaryBumble bees are important and widespread insect pollinators who face many environmental challenges. For example, bees are exposed to the metalloid selenate when foraging on pollen and nectar from plants growing in contaminated soils. As it has been shown that the microbiome of animals reduces metalloid toxicity, we assayed the ability of the bee microbiome to increase survivorship against selenate challenge. We exposed uninoculated or microbiota‐inoculated Bombus impatiens workers to a field‐realistic dose of 0.75 mg l−1 selenate and found that microbiota‐inoculated bees survive slightly but significantly longer than uninoculated bees. Using 16S rRNA gene sequencing, we found that selenate exposure altered gut microbial community composition and relative abundance of specific core bacteria. We also grew two core bumble bee microbes – Snodgrassella alvi and Lactobacillus bombicola – in selenate‐spiked media and found that these bacteria grew in the tested concentrations of 0.001–10 mg l−1 selenate. Furthermore, the genomes of these microbes harbour genes involved in selenate detoxification. The bumble bee microbiome slightly increases survivorship when the host is exposed to selenate, but the specific mechanisms and colony‐level benefits under natural settings require further study.
Separating noise from signal:
Authors: WILF EITAN 
Published: April 2019

ABSTRACTBecause ethnomethodology was founded in cybernetics, it institutionalized the idea that interactants strive to maintain interactional order and compensate for disorder through negative feedback mechanisms such as “repair work.” This idea informed a key strand in the study of human‐machine interaction in the United States, especially the idea that humans are inclined to repair the gaps in machines’ behavior and thus sustain the feeling that they are interacting with intentional entities. In some situations, however, humans prefer to expose and even exacerbate machines’ interactional incompetence. Such a preference manifests the aesthetic category of the uncanny, here theorized as the sudden awareness of the material foundations of one's immediate world, an awareness that emerges when those foundations become “noisy” and begin to reflexively point to themselves.
Burnout: Can we help?
Authors: Menahem Samuel 
Published: April 2019

AbstractThe recent editorial highlighting factors that may lead to burnout among the paediatric fraternity drew attention to those at most risk. They included ‘intelligent, committed, single young women’ more so then men and those who were ‘high achievers with empathy who take the patients' problems to heart’. Yet little appears to be available to ameliorate the stresses experienced by clinicians while building their resilience and improving their understanding of the interactions between themselves and the patient/parents. Drawing on past experience, a psychologically orientated approach to clinical care is emphasised. This approach required greater knowledge of one's self together with the need to commune with like‐minded colleagues. That led to a Balint‐type weekly group led by a child psychiatrist where experiences were exchanged, new knowledge acquired and mutual support provided. That in turn led to further study and the acquisition of new skills, including ongoing supervision to achieve a therapeutic interview. The latter was facilitated by carefully listening to the patient/parent, recognising the hidden agenda, struggling with non‐compliant parents and appreciating concepts such as transference and counter‐transference as it related to the patient–doctor interaction. Such insights may help paediatricians improve their therapeutic effectiveness and increase their personal satisfaction, thus adding a bonus to the essential requirement of a knowledge‐based diagnosis and management plan. Yet, only a few avenues are available to acquire such experiences, which need to be made available not only to those who recognise their importance but to all. How best to achieve these goals remains unresolved.