bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis of Tubulin Recruitment and Assembly by Tumor Overexpressed Gene (TOG) domain array Microtubule Polymerases
Authors: Nithianantham Stanley , Cook Brian D , Chang Fred , Al-Bassam Jawdat 
Published: June 2018

AbstractXMAP215/Stu2/Alp14 proteins accelerate microtubule plus-end polymerization by recruiting tubulins via arrays of Tumor Overexpressed Gene (TOG) domains. The underlying mechanism of these arrays as microtubule polymerases remains unknown. Here, we describe the biochemical and structural basis for TOG domain arrays in recruiting and polymerizing tubulins. Alp14 binds four tubulins via dimeric TOG1-TOG2 arrays, each with distinct exchange rates. X-ray structures reveal pseudo-dimeric square-shaped assemblies in which four TOG domains position four unpolymerized tubulins in a polarized wheel-like configuration. Crosslinking confirms square assemblies form in solution, and inactivation of their interfaces destabilizes square organizations without influencing tubulin binding. Using an approach to modulate tubulin polymerization, we determined a X-ray structure showing an unfurled assembly in which TOG1 and TOG2 uniquely bind two polymerized tubulins. Our findings suggest a new microtubule polymerase model in which TOG arrays recruit tubulins by forming square assemblies, which then unfurl facilitating their concerted polymerization into protofilaments.
Human Connectome Project resting state fMRI data organized into 60 fine-scaled retinotopically organized regions in cortical areas V1, V2 and V3
Authors: Dawson Debra Ann , Yin Zixuan , Lam Jack , Shmuel Amir 
Published: June 2018

AbstractThe data comprises 60 regions of interest (ROIs) from V1, V2, and V3 of the human visual cortex. Preprocessed data from the Human Connectome Project (HCP) 900 subjects public data release were utilized: 220 subjects were randomly selected, each with 4 scans of resting state fMRI data. Given that these subjects did not have retinotopy scans performed, the visual areas were defined using an anatomical template from Benson et al. (2014). Visual areas from each hemisphere were further divided along dorsal-ventral lines into quadrants, resulting in 4 quadrants per subject. Within each quadrant, fine scaled ROIs were defined by subdividing each visual area into 5 regions according to eccentricity. These data may be useful for studying retinotopically organized functional connectivity in the visual cortex using the HCP 3 Tesla dataset.
Chromatin interactions and expression quantitative trait loci reveal genetic drivers of multimorbidities
Authors: Fadason Tayaza , Schierding William , Lumley Thomas , O’Sullivan Justin M. 
Published: June 2018

AbstractClinical studies of non-communicable diseases identify multimorbidities that reflect our relatively limited fixed metabolic capacity. Despite the fact that we have ∼24000 genes, we do not understand the genetic pathways that contribute to the development of multimorbid non-communicable disease. We created a “multimorbidity atlas” of traits based on pleiotropy of spatially regulated genes using convex biclustering. Using chromatin interaction and expression Quantitative Trait Loci (eQTL) data, we analysed 20,782 variants (p < 5 × 10−6) associated with 1,351 phenotypes, to identify 16,248 putative eQTL-eGene pairs that are involved in 76,013 short- and long-range regulatory interactions (FDR < 0.05) in different human tissues. Convex biclustering of eGenes that are shared between phenotypes identified complex inter-relationships between nominally different phenotype associated SNPs. Notably, the loci at the centre of these inter-relationships were subject to complex tissue and disease specific regulatory effects. The largest cluster, 40 phenotypes that are related to fat and lipid metabolism, inflammatory disorders, and cancers, is centred on the FADS1-FADS3 locus (chromosome 11). Our novel approach enables the simultaneous elucidation of variant interactions with genes that are drivers of multimorbidity and those that contribute to unique phenotype associated characteristics.
3D Reconstruction of Bird Flight Trajectories Using a Single Video Camera
Authors: Srinivasan M.V. , Vo H.D. , Schiffner I. 
Published: June 2018

ABSTRACTVideo cameras are finding increasing use in the study and analysis of bird flight over short ranges. However, reconstruction of flight trajectories in three dimensions typically requires the use of multiple cameras and elaborate calibration procedures. We present an alternative approach that uses a single video camera and a simple calibration procedure for the reconstruction of such trajectories. The technique combines prior knowledge of the wingspan of the bird with a camera calibration procedure that needs to be used only once in the lifetime of the system. The system delivers the exact 3D coordinates of the position of the bird at the time of every full wing extension and uses interpolated height estimates to compute the 3D positions of the bird in the video frames between successive wing extensions. The system is inexpensive, compact and portable, and can be easily deployed in the laboratory as well as the field.
Blocking the alternative sigma factor RpoN reduces virulence ofPseudomonas aeruginosaisolated from cystic fibrosis patients and increases antibiotic sensitivity in a laboratory strain
Authors: Lloyd MG , Vossler JL , Nomura CT , Moffat JF 
Published: June 2018

AbstractMultidrug-resistant organisms (MDROs) are increasing in the health care setting, and there are few antimicrobial agents available to treat infections caused by these bacteria.Pseudomonas aeruginosais an opportunistic pathogen in burn patients and individuals with cystic fibrosis (CF), and a leading cause of nosocomial infections.P. aeruginosais inherently resistant to many antibiotics and can develop or acquire resistance to others, limiting options for treatment.P. aeruginosahas virulence factors that are regulated by sigma factors in response to the tissue microenvironment. The alternative sigma factor, RpoN (σ54), regulates many virulence genes and is linked to antibiotic resistance. Recently, we described a cis-acting peptide, RpoN*, which acts as a “molecular roadblock”, binding RpoN consensus promoters at the −24 site and blocking transcription. RpoN* reduces virulence ofP. aeruginosalaboratory strains bothin vitroandin vivo,but its effects in clinical isolates was not known. We investigated the effects of RpoN* on phenotypically variedP. aeruginosastrains isolated from cystic fibrosis patients. RpoN* expression reduced motility, biofilm formation, and pathogenesis in aP. aeruginosa – C. elegansinfection model. RpoN* expression increased susceptibility to several beta-lactam based antibiotics in the lab strainP. aeruginosaPA19660Xen5. Here, we show that using a cis-acting peptide to block RpoN consensus promoters has potential clinical implications in reducing virulence and enhancing the activity of antibiotics.
The probiotic effectiveness in experimental colitis is correlated with gut microbiome and host genetic features
Authors: Suwal Sharmila , Wu Qiong , Liu Wenli , Liu Qingya , Sun Hongxiang , Liang Ming , Gao Jing , Zhang Bo , Kou Yanbo , Liu Zhuanzhuan , Wei Yanxia , Wang Yugang , Zheng Kuiyang 
Published: June 2018

AbstractCurrent evidence to support extensive use of probiotics in inflammatory bowel disease is limited and factors contribute to the inconsistent effectiveness of clinical probiotic therapy are not completely known. Here, as a proof-of-concept, we utilized Bifidobacterium longum JDM 301, a widely used commercial probiotic strain in China, to study potential factors that may influence the beneficial effect of probiotics in experimental colitis. We found that the probiotic therapeutic effect was varied across individual mouse even with the same genetic background and consuming the same type of food. The different probiotic efficacy was highly correlated with different microbiome features in each mouse. Consumption of a diet rich in fat can change the host sensitivity to mucosal injury-induced colitis but did not change the host responsiveness to probiotic therapy. Finally, the host genetic factor TLR2 was required for a therapeutic effect of B. longum JDM 301. Together, our results suggest that personalized microbiome and genetic features may modify the probiotic therapeutic effect.
Regulation of EGFR endocytosis by CBL during mitosis
Authors: Wee Ping , Wang Zhixiang 
Published: June 2018

ABSTRACTEndocytosis plays important roles in regulating EGFR signaling. We previously found that EGFR endocytosis during mitosis is mediated differently than during interphase. While the regulation of EGFR endocytosis in interphase is well understood, little is known regarding the regulation of EGFR endocytosis during mitosis. Here, we studied the mechanisms regulating mitotic EGFR endocytosis. We found that contrary to interphase cells, mitotic EGFR endocytosis is more reliant on the activation of the E3 ligase CBL. At high EGF doses, inhibition of inhibited EGFR endocytosis of mitotic cells, but not of interphase cells. Moreover, the endocytosis of mutant EGFR Y1045F-YFP was strongly delayed. The endocytosis of truncated EGFR Δ1044-YFP that does not bind to CBL was completely inhibited. EGF induced stronger ubiquitination of mitotic EGFR than interphase EGFR and mitotic EGFR is trafficked to lysosome for degradation. Furthermore, during mitosis low doses of EGF also stimulate EGFR endocytosis by NCE. Contrary to interphase, CBL and the CBL-binding regions of EGFR were required for mitotic EGFR endocytosis at low doses. This may be due to the mitotic ubiquitination of the EGFR even at low EGF doses. In conclusion, mitotic EGFR endocytosis solely proceed through CBL-mediated NCE.
The fungal-specific Hda2 and Hda3 proteins regulate morphological switches in the human fungal pathogenCandida albicans
Authors: Peterson Misty R. , Price Robert Jordan , Gourlay Sarah , May Alisha , Tullet Jennifer , Buscaino Alessia 
Published: June 2018

ABSTRACTThe human fungal pathogenCandida albicansis responsible for millions of infections annually. Due to the few available anti-fungal drugs and the increasing incidence of drug resistance, the number ofC. albicansinfections is dramatically increasing. Morphological switches, such as the white-opaque switch and the yeast-hyphae switch, are key for the development ofC. albicanspathogenic traits. Lysine deacetylases are emerging as important regulators of morphological switches. Yet, targeting lysine deacetylases for drug development is problematic due to the high homology between the fungal and human proteins that could result in toxicity. Here we provide evidence that the fungal specific proteins Hda2 and Hda3 interact with the lysine deacetylase Hda1. By combining phenotypic analyses with genome-wide transcriptome analyses, we demonstrate that Hda2 and Hda3 controlC. albicansmorphological switches. Under nutrient-rich conditions, deletion ofHDA2orHDA3leads to moderate overexpression of the master regulator of white-opaque switchingWOR1and increase switching frequency. Under hyphae inducing conditions, deletion ofHDA2andHDA3block hyphae development. However, deletion ofHDA2andHDA3does not affect hyphae-formation and virulencein vivo. We propose that Hda2 and Hda3 are good targets for the development of anti-fungal drugs to be used in combination therapy.
“Small and many” is the strategy for robust and efficient information transfer in dendritic spines
Authors: Tottori Takehiro S. , Fujii Masashi , Kuroda Shinya 
Published: June 2018

AbstractA dendritic spine is a small structure on the dendrites of a neuron that processes input timing information from other neurons. Tens of thousands of spines are present on a neuron. Why are spines so small and many? Because of the small number of molecules in the spine volume, biochemical reactions become stochastic. Therefore, we used the stochastic simulation model of N-methyl-D-aspartate receptor (NMDAR)-mediated Ca2+ increase to address this issue. NMDAR-mediated Ca2+ increase codes the input timing information between prespiking and postspiking. We examined how much the input timing information is encoded by Ca2+ increase against prespiking fluctuation. We found that the input timing information encoded in the spine volume (10-1 μm3) is more robust against prespiking fluctuation than that in the cell volume (103 μm3). We further examined the mechanism of the robust information transfer in the spine volume. We demonstrated that the necessary and sufficient condition for robustness is that the stochastic NMDAR-mediated Ca2+ increase (intrinsic noise) becomes much larger than the prespiking fluctuation (extrinsic noise). The condition is satisfied in the spine volume, but not in the cell volume. Moreover, we compared the information transfer in many small “spine-volume” spines with that in a single large “cell-volume” spine. We found that many small “spine-volume” spines is much more efficient for information transfer than a single large “cell-volume” spine when prespiking fluctuation is large. Thus, robustness and efficiency are two functional reasons why dendritic spines are so small and many.SignificanceA dendritic spine is a small platform for information processing in a neuron, and tens of thousands of spines are present on a neuron. Why are spines so small and many? Here we addressed this issue using stochastic simulation of NMDAR-mediated Ca2+ increase in a spine. We demonstrated that smallness of a spine enables the robust information transfer against input fluctuation, and that many small spines are much efficient for information transfer than a single large cell. This is the first demonstration that shows the advantage of the “small and many” of spines in information processing. The “small and many” strategy may be used not only in spines of a neuron, but also in other small and many intracellular organelles.
ER shaping proteins regulate mitochondrial fission, outer membrane permeabilization and apoptosis
Authors: Milani Mateus , Cohen Gerald M , Varadarajan Shankar 
Published: June 2018

AbstractThe mitochondrial fission machinery, comprising a dynamin-related GTPase, DRP-1, is crucial for the regulation of mitochondrial membrane dynamics. Recent reports suggest that the tubular architecture of the endoplasmic reticulum (ER) marks the constriction sites on the mitochondria to facilitate DRP-1-mediated mitochondrial fission. However, the role of several ER shaping proteins that maintain the elaborate network of tubes and sheets in mitochondrial constriction and fission is not yet known. In this report, we demonstrate that modulation of the expression levels of key ER shaping proteins, namely Reticulon1 (RTN-1), Reticulon 4 (RTN-4), Lunapark-1 (LNP-1) and CLIMP-63, markedly decreased the extent of mitochondrial fission mediated by BH3 mimetics, despite no detectable changes in DRP-1 recruitment to the mitochondria. Furthermore, modulation of ER shaping proteins significantly decreased other hallmarks of apoptosis, such as mitochondrial outer membrane permeabilization, caspase activation and phosphatidylserine externalization, and functioned independently of mitochondrial cristae remodeling, thus demonstrating a requirement of ER shaping proteins and ER structural integrity for the efficient execution of the instrinsic apoptotic pathway.
Effects of sublethal concentrations and application concentration of SYP-9625 on Tetranychus cinnabarinus (Boisduval) and its natural enemy, Neoseiulus californicus (McGregor)
Authors: Ouyang Jingqi , Tian Yajing , Jiang Chunxian , Yang Qunfang , Wang Haijian , Li Qing 
Published: June 2018

AbstractObjectiveExploring the effects of acaricides on predatory mites is crucial for the combination of biological and chemical control of pests. In this study, sublethal effects of the new acaricide SYP-9625 on Tetranychus cinnabarinus (Boisduval), effects of application concentration of SYP-9625 on the predatory mite Neoseiulus californicus (McGregor) and functional responses of N. californicus were assessed. The aim of the present study was to evaluate and explore the application of new acaricide SYP-9625 with natural enemy N. californicus.MethodAll the experiments were under laboratory conditions [25 ± 1 °C, 16:8 (L:D) h and 75 ± 5% RH] and based on an age-stage, two-sex life table. The sublethal concentrations against T. cinnabarinus, including LC10 (0.375 μg/mL) and LC30 (0.841 μg/mL) and the application concentration (100 μg/mL) of SYP-9625, were used to evaluate effects on population parameters of N. californicus.ResultT. cinnabarinus females treated with LC30 exhibited significantly reduced net reproductive rates (R0=11.02) of offspring compared to females treated with LC10 (R0=14.96) and untreated females (>R0=32.74). However, the intrinsic rate of increase (rm) and finite rate of increase (λ) of N. californicus indicated that the application concentration of SYP-9625 had no significant negative effect on treated N. californicus eggs (rm=0.277, λ=1.319) compared to the control (rm=0.292, λ=1.338). Additionally, the sublethal concentrations against T. cinnabarinus including LC10 and LC30 showed a dose-dependent mechanism on the predatory mite. SYP-9625 also stimulated the predatory capacity of N. californicus against immobile stages such as eggs and larvae.ConclusionIt is demonstrated that sublethal concentrations of SYP-9625 can inhibit population growth of T. cinnabarinus. And the sublethal concentrations and application concentration had little effect on the population growth of N. californicus. The two advantages showed great commercial potential of this new acaricide. Therefore, N. californicus can manage T. cinnabarinus populations effectively with appropriate SYP-9625 concentrations.
Assessment of self stigma and medication adherence among patients with mental illness who had been treated at Jimma University Specialized Hospital, South west Ethiopia: community based cross sectional study, 2017
Authors: Golja Eba Abdisa , Girma Shimelis 
Published: June 2018

AbstractBackgroundself Stigma associated with psychiatric disorders and its treatment toward patients with mental illness is the main challengers for early and successful treatment outcome.ObjectiveTo assess the association between self stigma and level of medication adherence among patients with mental illness who have been treated at psychiatric clinic, JUSH, South West Ethiopia, 2017.MethodsThis study is a community based cross sectional study design using a case tracing method to identify patients in the community. To get the study subject, tracing method was carried to get the patients who had history of treatment at psychiatric clinic, Jimma University Teaching Hospital. Interview based Questionnaire was used to get information from the participants. The relationship was checked by doing both bivariate and multi variables linear regression.ResultOf the total respondents, males were185 (61.7%), females 115 (38.3%), and the mean age of the respondents was 34.99 (SD=11.51) years. From the total (n=300) respondents, more than half of them, 182 (60.7%) were adherent to their psychotropic medication. Among adherent respondents, of all types of stigma, minimal stigma was 63.2% whereas moderate to high stigma was 22.4%.ConclusionIt was identified that there was high self stigma related to medication non adherent among patients with mental illness. Therefore, mental health professionals and the health care policy shall work to increase the level of psychotropic medication adherence so as to decrease self stigma associated with mental illness.
Software-aided workflow for predicting protease-specific cleavage sites using physicochemical properties of the natural and unnatural amino acids in peptide-based drug discovery: Peptide cleavage sites prediction workflow
Authors: Radchenko Tatiana , Fontaine Fabien , Morettoni Luca , Zamora Ismael 
Published: June 2018

AbstractPeptide drugs have been used in the treatment of multiple pathologies. During peptide discovery, it is crucially important to be able to map the potential sites of cleavages of the proteases. This knowledge is used to later chemically modify the peptide drug to adapt it for the therapeutic use, making peptide stable against individual proteases or in complex medias. In some other cases it needed to make it specifically unstable for some proteases, as peptides could be used as a system to target delivery drugs on specific tissues or cells. The information about proteases, their sites of cleavages and substrates are widely spread across publications and collected in databases such as MEROPS. Therefore, it is possible to develop models to improve the understanding of the potential peptide drug proteolysis. We propose a new workflow to derive protease specificity rules and predict the potential scissile bonds in peptides for individual proteases. WebMetabase stores the information from experimental or external sources in a chemically aware database where each peptide and site of cleavage is represented as a sequence of structural blocks connected by amide bonds and characterized by its physicochemical properties described by Volsurf descriptors. Thus, this methodology could be applied in the case of non-standard amino acid. A frequency analysis can be performed in WebMetabase to discover the most frequent cleavage sites. These results were used to train several models using logistic regression, support vector machine and ensemble tree classifiers to map cleavage sites for several human proteases from four different families (serine, cysteine, aspartic and matrix metalloproteases). Finally, we compared the predictive performance of the developed models with other available public tools PROSPERous and SitePrediction.