bluuebunny/crossref_metadata_2025_split huggingface dataset:
The H3K9 methyltransferase SETDB1 maintains female identity in Drosophila germ cells
Authors: Smolko Anne E. , Shapiro-Kulnane Laura , Salz Helen K. 
Published: October 2018

AbstractThe preservation of germ cell sexual identity is essential for gametogenesis. Here we show that H3K9me3-mediated gene silencing is integral to female fate maintenance in Drosophila germ cells. Germ cell specific loss of the H3K9me3 pathway members, the H3K9 methyltransferase SETDB1, WDE, and HP1a, leads to ectopic expression of genes, many of which are normally expressed in testis. SETDB1 controls the accumulation of H3K9me3 over a subset of these genes without spreading into neighboring loci. At phf7, a regulator of male germ cell sexual fate, the H3K9me3 peak falls over the silenced testis-specific transcription start site. Furthermore, H3K9me3 recruitment to phf7 and repression of testis-specific transcription is dependent on the female sex determination gene Sxl. Thus, female identity is secured by an H3K9me3 epigenetic pathway in which Sxl is the upstream female-specific regulator, SETDB1 is the required chromatin writer, and phf7 is one of the critical SETDB1 target genes.
Sparsened neuronal activity in an optogenetically activated olfactory glomerulus
Authors: Braubach Oliver , Tombaz Tuce , Geiller Tristan , Homma Ryota , Bozza Thomas , Cohen Lawrence B. , Choi Yunsook 
Published: October 2018

AbstractGlomeruli are the functional units of olfactory information processing but little remains known about their individual unit function. This is due to their widespread activation by odor stimuli. We expressed channelrhodopsin-2 in a single olfactory sensory neuron type, and used laser stimulation and simultaneous in vivo calcium imaging to study the responses of a single glomerulus to optogenetic stimulation. Calcium signals in the neuropil of this glomerulus were representative of the sensory input and nearly identical if evoked by intensity-matched odor and laser stimuli. However, significantly fewer glomerular layer interneurons and olfactory bulb output neurons (mitral cells) responded to optogenetic versus odor stimuli, resulting in a small and spatially compact optogenetic glomerular unit response. Temporal features of laser stimuli were represented with high fidelity in the neuropil of the glomerulus and the mitral cells, but not in interneurons. Increases in laser stimulus intensity were encoded by larger signal amplitudes in all compartments of the glomerulus, and by the recruitment of additional interneurons and mitral cells. No spatial expansion of the glomerular unit response was observed in response to stronger input stimuli. Our data are among the first descriptions of input-output transformations in a selectively activated olfactory glomerulus.
Hydrophobic alkyl chains substituted to the 8-position of cyclic nucleotides enhance activation of CNG and HCN channels by an intricate enthalpy - entropy compensation
Authors: Otte Maik , Schweinitz Andrea , Bonus Michele , Enke Uta , Schumann Christina , Gohlke Holger , Benndorf Klaus 
Published: October 2018

AbstractCyclic nucleotide-gated (CNG) and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are tetrameric non-specific cation channels in the plasma membrane that are activated by either cAMP or cGMP binding to specific binding domains incorporated in each subunit. Typical apparent affinities of these channels for these cyclic nucleotides range from several hundred nanomolar to tens of micromolar. Here we synthesized and characterized novel cAMP and cGMP derivatives by substituting either hydrophobic alkyl chains or similar-sized more hydrophilic heteroalkyl chains to the 8-position of the purine ring with the aim to obtain full agonists of higher potency. The compounds were tested in homotetrameric CNGA2, heterotetrameric CNGA2:CNGA4:CNGB1b and homotetrameric HCN2 channels. We show that nearly all compounds are full agonists and that longer alkyl chains systematically increase the apparent affinity, at the best more than 30 times. The effects are stronger in CNG than HCN2 channels which, however, are constitutively more sensitive to cAMP. Kinetic analyses reveal that the off-rate is significantly slowed by the hydrophobic alkyl chains. Molecular dynamics simulations and free energy calculations suggest that an intricate enthalpy - entropy compensation underlies the higher apparent affinity of the derivatives with the longer alkyl chains, which is shown to result from a reduced loss of configurational entropy upon binding.
Quinoa whole grain diet compromises the changes of gut microbiota and colonic colitis induced by dextran Sulfate sodium in C57BL/6 mice
Authors: Liu Wei , Zhang Yu , Qiu Bin , Fan Shoujin , Ding Hanfeng , Liu Zhenhua 
Published: October 2018

AbstractA plethora of evidence highlights that the dysbiosis of gut microbiota is a critical factor for inflammatory bowel disease (IBD). Both in vivo and in vitro studies have demonstrated that quinoa possesses potential prebiotic effects. The present study aims to examine the potential in using quinoa to ameliorate the dysbiosis and colitis induced by dextran sodium sulfate (DSS). A total of 40 C57BL/6 mice were fed either an AIN-93M diet or a quinoa-based diet, separately. Colitis was induced for 10 animals/dietary group with a 5-days exposure to 2.5% DSS. The clinical symptoms were monitored every other day, and the gut microbiota was characterized by 16S rRNA gene sequencing. The results indicated that consumption of quinoa lessened clinical symptoms as indicated by the reduced disease activity index and the degree of histological damage (P < 0.05). As expected, the DSS treatment induced significant dysbiosis of gut microbiota in mice on an AIN-93M diet. However, compared to mice fed the AIN-93M diet, the consumption of quinoa alleviated the DSS-induced dysbiosis remarkably, as indicated by increased species richness and diversity, decreased abnormal expansion of phylum Proteobacteria, and decreased overgrowth of genera Escherichia/Shigella and Peptoclostridium (P < 0.05). The relative abundances of Firmicutes and Bacteroidetes were less altered in mice fed with quinoa comparing to those mice fed the AIN-93M diet. In summary, the consumption of quinoa suppressed the dysbiosis of gut microbiota and alleviated clinical symptoms induced by DSS, indicating the potential to utilize quinoa as a dietary approach to improve intestinal health.
Age-Related Measurements of the Myelin Water Fraction derived from 3D multi-echo GRASE reflect Myelin Content of the Cerebral White Matter
Authors: Faizy Tobias D. , Kumar Dushyant , Broocks Gabriel , Thaler Christian , Flottmann Fabian , Leischner Hannes , Kutzner Daniel , Hewera Simon , Dotzauer Dominik , Stellmann Jan-Patrick , Reddy Ravinder , Fiehler Jens , Sedlacik Jan , Gellißen Susanne 
Published: October 2018

AbstractMyelin Water Fraction (MWF) measurements derived from quantitative Myelin Water Imaging (MWI) may detect demyelinating changes of the cerebral white matter (WM) microstructure. Here, we investigated age-related alterations of the MWF in normal aging brains of healthy volunteers utilizing two fast and clinically feasible 3D gradient and spin echo (GRASE) MWI sequences with 3 mm and 5 mm isotropic voxel size. In 45 healthy subjects (age range: 18–79 years), distinct regions of interest (ROI) were defined in the cerebral WM including corticospinal tracts. For the 3 mm sequence, significant correlations of the mean MWF with age were found for most ROIs (r < −0.8 for WM ROIs; r = −0.55 for splenium of corpus callosum; r = −0.75 for genu of corpus callosum; p < 0.001 for all ROIs). Similar correlations with age were found for the ROIs of the 5 mm sequence. No significant correlations were found for the corticospinal tract and the occipital WM (p > 0.05). Mean MWF values obtained from the 3 mm and 5 mm sequences were strongly comparable. The applied 3D GRASE MWI sequences were found to be sensitive for age-dependent myelin changes of the cerebral WM microstructure. The reported MWF values might be of substantial use as reference for further investigations in patient studies.
Prevalence of the Metabolic Syndrome and its determinants among Nepalese adults: Findings from a nationally representative cross-sectional study
Authors: Mehata Suresh , Shrestha Nipun , Mehta Ranju Kumari , Bista Bihungum , Pandey Achyut Raj , Mishra Shiva Raj 
Published: October 2018

AbstractMetabolic syndrome (MetS) increases the risk of cardiovascular diseases and diabetes mellitus. This study is designed to assess the prevalence and determinants of MetS among Nepalese adults from a nationally representative study. This study is based on Stepwise Approach to Surveillance (STEPS) Survey from Nepal. This survey was done among 4200 adults aged 15–69 years from 210 clusters selected proportionately across Nepal’s three ecological zones (Mountain, Hill and Terai). Subsequently, using systematic sampling, twenty households per cluster and one participant per household were selected. The overall prevalence of MetS is 15% and 16% according to Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) criteria respectively. A triad of low HDL-C, abdominal obesity and high BP was the most prevalent (8.18%), followed by abdominal obesity, low HDL-C cholesterol and high triglycerides (8%). Less than two percent of participants had all the five components of the syndrome and 19% of participants had none. The prevalence steadily rose across the age group with adults aged 45–69 years having the highest prevalence (28–30%) and comparable prevalence across two definitions of MetS. A notably high burden for females, urban, hill or Terai resident were seen among other factors.
Sexual Arousal Patterns of Identical Twins with Discordant Sexual Orientations
Authors: Watts Tuesday M. , Holmes Luke , Raines Jamie , Orbell Sheina , Rieger Gerulf 
Published: October 2018

AbstractGenetically identical twins can differ in their self-reported sexual orientations. However, whether the twins’ subjective reports reflect valid differences in their sexual orientations is unknown. Measures of sexual orientation, which are free of the limitations of self-report, include genital arousal and pupil dilation while viewing sexual stimuli depicting men or women. We examined these responses in 6 male twin pairs and 9 female twin pairs who reported discordant sexual orientations. Across measures, heterosexual male twins responded more strongly to women than to men. Their homosexual co-twins showed an opposite pattern. Heterosexual female twins responded equally to both sexes, whereas their homosexual co-twins responded somewhat more to women than men. These differences within pairs were similar to differences between unrelated heterosexual and homosexual males and females. Our study provides physiological evidence confirming twins’ discordant sexual orientations, thereby supporting the importance of the non-shared environment for the development of sexual orientation and sexual arousal.
The mycoparasitic yeast Saccharomycopsis schoenii predates and kills multi-drug resistant Candida auris
Authors: Junker Klara , Bravo Ruiz Gustavo , Lorenz Alexander , Walker Louise , Gow Neil A. R. , Wendland Jürgen 
Published: October 2018

AbstractCandida auris has recently emerged as a multi-drug resistant fungal pathogen that poses a serious global health threat, especially for patients in hospital intensive care units (ICUs). C. auris can colonize human skin and can spread by physical contact or contaminated surfaces and equipment. Here, we show that the mycoparasitic yeast Saccharomycopsis schoenii efficiently kills both sensitive and multi-drug resistant isolates of C. auris belonging to the same clade, as well as clinical isolates of other pathogenic species of the Candida genus suggesting novel approaches for biocontrol.
Transcriptomic analysis reveals a controlling mechanism for NLRP3 and IL-17A in dextran sulfate sodium (DSS)-induced colitis
Authors: Lin Tien-Jen , Yin Shu-Yi , Hsiao Pei-Wen , Yang Ning-Sun , Wang I-Jen 
Published: October 2018

AbstractThe incidence of inflammatory bowel disease (IBD) has markedly increased. Our research findings during the past showed that medicinal plant extracts and the derived phytochemical components from Wedelia chinensis (WC) can have strong anti-colitis activities. Here, we further identified the key component phytochemicals from active fractions of different WC preparations (WCHA) that are responsible for the protective effect of WCHA in colitis mice. Of the 3 major compounds (wedelolactone, luteolin and apigenin) in this fraction, luteolin had the highest anti-inflammatory effect in vivo. Using a next-generation sequencing (NGS) (e.g., RNA-seq) system to analyze the transcriptome of colorectal cells/tissues in mice with dextran sulfate sodium (DSS)-induced colitis with/without phytochemicals treatment, luteolin was found to strongly suppress the DSS-activated IL-17 pathway in colon tissue. In addition, co-treatment with wedelolactone and luteolin had a synergistic effect on the expression level of some IL-17 pathway-related genes. Interestingly, our NGS analyses also indicated that luteolin and wedelolactone can specifically suppress the expression of NLRP3 and NLRP1. Using a 3-dimensional cell co-culture system, we further demonstrated that luteolin could efficiently suppress NLRP3 expression via disruption of IL-17A signaling in inflamed colon tissue, which also indicates the pharmacological potential of luteolin and wedelolactone in treating IBD.
Extraction and liposome reconstitution of membrane proteins with their native lipids without the use of detergents
Authors: Smirnova Irina A. , Ädelroth Pia , Brzezinski Peter 
Published: October 2018

AbstractFunctional studies of membrane-bound channels, transporters or signal transducers require that the protein of interest resides in a membrane that separates two compartments. One approach that is commonly used to prepare these systems is to reconstitute the protein in liposomes. An intermediate step of this method is purification of the protein, which typically involves solubilization of the native membrane using detergent. The use of detergents often results in removal of lipids surrounding the protein, which may alter its structure and function. Here, we have employed a method for isolation of membrane proteins with a disc of their native lipids to develop an approach that allows transfer of the purified membrane protein to liposomes without the use of any detergents.
CHI3L1 promotes tumor progression by activating TGF-β signaling pathway in hepatocellular carcinoma
Authors: Qiu Qing-Chong , Wang Lin , Jin Shan-Shan , Liu Guan-Feng , Liu Jie , Ma Liang , Mao Rui-Fang , Ma Ying-Ying , Zhao Na , Chen Ming , Lin Biao-Yang 
Published: October 2018

AbstractCHI3L1 (YKL40) is a secreted glycoprotein and elevated serum CHI3L1 level has been proved to be associated with poor prognosis in many human cancers. However, the mechanism of how CHI3L1 causes poor prognosis in cancers is still unknown. Here, considering that CHI3L1 is a liver specific/enriched protein, we use hepatocellular carcinoma as a model to study the function of CHI3L1. We showed that, both in vivo and in vitro, overexpression of CHI3L1 could promote liver cancer cells growth, migration and invasion. We then used RNA-seq to analyze the expression profiles of CHI3L1 overexpressed in two HCC cell lines and found that CHI3L1 overexpression affected genes that were involved in cell-cell adhesion, extracellular exosome and adherens junction. Western blot analysis further revealed that CHI3L1 could activate TGF-β signal pathways. Our data added new understanding of the mechanism of CHI3L1’s action. 1) CHI3L1 promoted cancer cell proliferation by regulating cell cycles; 2) CHI3L1 promoted cancer cell invasion and metastasis; 3) CHI3L1 regulate liver cancer potentially by regulating the TGF-β signaling pathways; 4) CHI3L1 has direct kinase activities or activate kinase to phosphorylate SMAD2, SMAD3.
Regenerative potential of induced pluripotent stem cells derived from patients undergoing haemodialysis in kidney regeneration
Authors: Tajiri Susumu , Yamanaka Shuichiro , Fujimoto Toshinari , Matsumoto Kei , Taguchi Atsuhiro , Nishinakamura Ryuichi , Okano Hirotaka James , Yokoo Takashi 
Published: October 2018

AbstractKidney regeneration from pluripotent stem cells is receiving a lot of attention because limited treatments are currently available for chronic kidney disease (CKD). It has been shown that uremic state in CKD is toxic to somatic stem/progenitor cells, such as endothelial progenitor and mesenchymal stem cells, affecting their differentiation and angiogenic potential. Recent studies reported that specific abnormalities caused by the non-inherited disease are often retained in induced pluripotent stem cell (iPSC)-derived products obtained from patients. Thus, it is indispensable to first assess whether iPSCs derived from patients with CKD due to non-inherited disease (CKD-iPSCs) have the ability to generate kidneys. In this study, we generated iPSCs from patients undergoing haemodialysis due to diabetes nephropathy and glomerulonephritis (HD-iPSCs) as representatives of CKD-iPSCs or from healthy controls (HC-iPSCs). HD-iPSCs differentiated into nephron progenitor cells (NPCs) with similar efficiency to HC-iPSCs. Additionally, HD-iPSC-derived NPCs expressed comparable levels of NPC markers and differentiated into vascularised glomeruli upon transplantation into mice, as HC-iPSC-derived NPCs. Our results indicate the potential of HD-iPSCs as a feasible cell source for kidney regeneration. This is the first study paving the way for CKD patient-stem cell-derived kidney regeneration, emphasising the potential of CKD-iPSCs.
Toxoplasma gondii Manipulates Expression of Host Long Noncoding RNA during Intracellular Infection
Authors: Menard Kayla L. , Haskins Breanne E. , Colombo Anthony P. , Denkers Eric Y. 
Published: October 2018

AbstractLong noncoding RNA (lncRNA) are non-protein-coding transcripts greater than 200 nucleotides that regulate gene expression. The field of transcriptomics is only beginning to understand the role of lncRNA in host defense. Little is known about the role of lncRNA in the response to infection by intracellular pathogens such asToxoplasma gondii. Using a microarray, we examined the differential expression of 35,923 lncRNAs and 24,881 mRNAs in mouse bone-marrow-derived macrophages during infection with high- and low-virulenceT.gondiistrains. We found that 1,522 lncRNA molecules were differentially regulated during infection with the high-virulence Type I strain, versus 528 with the less-virulent Type II strain. Of these lncRNAs, 282 were co-regulated with a nearby or overlapping mRNA–including approximately 60 mRNAs with immune-related functions. We validated the microarray for 4 lncRNAs and 4 mRNAs using qRT-PCR. Using deletion strains ofT.gondii, we found that the secretory kinase ROP16 controls upregulation of lncRNAs Csf1-lnc and Socs2-lnc, demonstrating that the parasite directly manipulates host lncRNA expression. Given the number of regulated lncRNAs and the magnitude of the expression changes, we hypothesize that these molecules constitute both an additional regulatory layer in the host response to infection and a target for manipulation byT.gondii.
An optogenetic toolbox of LOV-based photosensitizers for light-driven killing of bacteria
Authors: Endres Stephan , Wingen Marcus , Torra Joaquim , Ruiz-González Rubén , Polen Tino , Bosio Gabriela , Bitzenhofer Nora Lisa , Hilgers Fabienne , Gensch Thomas , Nonell Santi , Jaeger Karl-Erich , Drepper Thomas 
Published: October 2018

AbstractFlavin-binding fluorescent proteins (FPs) are genetically encoded in vivo reporters, which are derived from microbial and plant LOV photoreceptors. In this study, we comparatively analyzed ROS formation and light-driven antimicrobial efficacy of eleven LOV-based FPs. In particular, we determined singlet oxygen (1O2) quantum yields and superoxide photosensitization activities via spectroscopic assays and performed cell toxicity experiments in E. coli. Besides miniSOG and SOPP, which have been engineered to generate 1O2, all of the other tested flavoproteins were able to produce singlet oxygen and/or hydrogen peroxide but exhibited remarkable differences in ROS selectivity and yield. Accordingly, most LOV-FPs are potent photosensitizers, which can be used for light-controlled killing of bacteria. Furthermore, the two variants Pp2FbFP and DsFbFP M49I, exhibiting preferential photosensitization of singlet oxygen or singlet oxygen and superoxide, respectively, were shown to be new tools for studying specific ROS-induced cell signaling processes. The tested LOV-FPs thus further expand the toolbox of optogenetic sensitizers usable for a broad spectrum of microbiological and biomedical applications.
Changing patterns of adult asthma incidence: results from the National Health Insurance Service–National Sample Cohort (NHIS-NSC) database in Korea
Authors: Shin Ji-Yeon , Sohn Kyoung-Hee , Shin Ji Eun , Park Mira , Lim Jiseun , Lee Jin Yong , Yang Min-Suk 
Published: October 2018

AbstractThis study was conducted to assess the changes in the annual incidence of adult asthma in Korea where the prevalence of asthma had increased steadily in recent decades. A population-based cohort study was conducted using the National Health Insurance Service–National Sample Cohort (NHIS-NSC), which consisted of 746,816 adults aged >20 years between 2004 and 2012. Asthma was defined by two or more physician claims on the basis of a primary diagnostic code for asthma and administration of asthma medications within 1 year. The incidence rates and annual percent change were calculated, and the influence of age and sex on the incidence rates was studied. The annual asthma incidence increased from 3.63 in 2004 to 6.07 per 1,000 person-years in 2008. Since 2008, the asthma incidence did not change significantly. The asthma incidence was higher in women than in men throughout the study periods (p < 0.001) and higher in older than younger age groups (p < 0.001). The asthma incidence did not change in all ages since 2008, except for the 20 s who showed a steady increase. The incidence of asthma in adults reached plateau in Korea, which is consistent with the results from studies in other countries.
Information transfer in QT-RR dynamics: Application to QT-correction
Authors: Potapov Ilya , Latukka Joonas , Kim Jiyeong , Luukko Perttu , Aalto-Setälä Katriina , Räsänen Esa 
Published: October 2018

AbstractThe relation between the electrical properties of the heart and the beating rate is essential for the heart functioning. This relation is central when calculating the “corrected QT interval” — an important measure of the risk of potentially lethal arrhythmias. We use the transfer entropy method from information theory to quantitatively study the mutual dynamics of the ventricular action potential duration (the QT interval) and the length of the beat-to-beat (RR) interval. We show that for healthy individuals there is a strong asymmetry in the information transfer: the information flow from RR to QT dominates over the opposite flow (from QT to RR), i.e. QT depends on RR to a larger extent than RR on QT. Moreover, the history of the intervals has a strong effect on the information transfer: at sufficiently long QT history length the information flow asymmetry inverts and the RR influence on QT dynamics weakens. Finally, we demonstrate that the widely used QT correction methods cannot properly capture the changes in the information flows between QT and RR. We conclude that our results obtained through a model-free informational perspective can be utilised to improve and test the QT correction schemes in clinics.