bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the replicability of cell types defined by single cell RNA-sequencing data using MetaNeighbor
Authors: Crow Megan , Paul Anirban , Ballouz Sara , Huang Z. Josh , Gillis Jesse 
Published: February 2018

AbstractSingle-cell RNA-sequencing (scRNA-seq) technology provides a new avenue to discover and characterize cell types; however, the experiment-specific technical biases and analytic variability inherent to current pipelines may undermine its replicability. Meta-analysis is further hampered by the use of ad hoc naming conventions. Here we demonstrate our replication framework, MetaNeighbor, that quantifies the degree to which cell types replicate across datasets, and enables rapid identification of clusters with high similarity. We first measure the replicability of neuronal identity, comparing results across eight technically and biologically diverse datasets to define best practices for more complex assessments. We then apply this to novel interneuron subtypes, finding that 24/45 subtypes have evidence of replication, which enables the identification of robust candidate marker genes. Across tasks we find that large sets of variably expressed genes can identify replicable cell types with high accuracy, suggesting a general route forward for large-scale evaluation of scRNA-seq data.
Implication of liver enzymes on incident cardiovascular diseases and mortality: A nationwide population-based cohort study
Authors: Choi Kyung Mook , Han Kyungdo , Park Sanghyun , Chung Hye Soo , Kim Nam Hoon , Yoo Hye Jin , Seo Ji-A , Kim Sin Gon , Kim Nan Hee , Baik Sei Hyun , Park Yong Gyu , Kim Seon Mee 
Published: February 2018

AbstractAlthough liver enzymes, such as γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), have recently been suggested as risk factors for cardiovascular diseases (CVD), impact on mortality after myocardial infarction (MI) or ischemic stroke (IS) was not previously examined. Using a population-based, nationwide cohort database, we explored the implication of GGT and aminotransferases on the development of CVD and all-cause mortality during a median 9.1 years of follow-up. Among 16,624,006 Korean adults, both GGT and aminotransferases exhibited a positive relationship with MI, IS, and mortality in a multivariate adjusted model. ALT and AST showed U-shaped associations with mortality, whereas GGT showed a positive linear relationship with mortality. The risk of 1-year mortality after MI or IS was significantly higher in the highest quartile of GGT compared to the lowest quartile (HR, 1.46; 95% CI, 1.40-1.52). The implication of GGT on MI, IS, and mortality persisted regardless of traditional cardiovascular risk parameters. This study demonstrated the unique pattern of association of ALT, AST, and GGT with the development of CVD and all-cause mortality in the Korean population. In particular, GGT showed the most robust linear relationship with mortality before and after cardiovascular events independent of risk factors.
Simulated microgravity inhibits cell focal adhesions leading to reduced melanoma cell proliferation and metastasis via FAK/RhoA-regulated mTORC1 and AMPK pathways
Authors: Tan Xin , Xu Aizhang , Zhao Tuo , Zhao Qin , Zhang Jun , Fan Cuihong , Deng Yulin , Freywald Andrew , Genth Harald , Xiang Jim 
Published: February 2018

AbstractSimulated microgravity (SMG) was reported to affect tumor cell proliferation and metastasis. However, the underlying mechanism is elusive. In this study, we demonstrate that clinostat-modelled SMG reduces BL6-10 melanoma cell proliferation, adhesion and invasiveness in vitro and decreases tumor lung metastasis in vivo. It down-regulates metastasis-related integrin α6β4, MMP9 and Met72 molecules. SMG significantly reduces formation of focal adhesions and activation of focal adhesion kinase (FAK) and Rho family proteins (RhoA, Rac1 and Cdc42) and of mTORC1 kinase, but activates AMPK and ULK1 kinases. We demonstrate that SMG inhibits NADH induction and glycolysis, but induces mitochondrial biogenesis. Interestingly, administration of a RhoA activator, the cytotoxic necrotizing factor-1 (CNF1) effectively converts SMG-triggered alterations and effects on mitochondria biogenesis or glycolysis. CNF1 also converts the SMG-altered cell proliferation and tumor metastasis. In contrast, mTORC inhibitor, rapamycin, produces opposite responses and mimics SMG-induced effects in cells at normal gravity. Taken together, our observations indicate that SMG inhibits focal adhesions, leading to inhibition of signaling FAK and RhoA, and the mTORC1 pathway, which results in activation of the AMPK pathway and reduced melanoma cell proliferation and metastasis. Overall, our findings shed a new light on effects of microgravity on cell biology and human health.
Disruption of the open conductance in the β-tongue mutants of Cytolysin A
Authors: Fahie Monifa A. , Liang Lucas , Avelino Alzira R. , Pham Bach , Limpikirati Patanachai , Vachet Richard W. , Chen Min 
Published: February 2018

AbstractCytolysin A (ClyA) is a water-soluble alpha pore-forming toxin that assembles to form an oligomeric pore on host cell membranes. The ClyA monomer possesses an α-helical bundle with a β-sheet subdomain (the β-tongue) previously believed to be critical for pore assembly and/or insertion. Oligomerization of ClyA pores transforms the β-tongue into a helix-turn-helix that embeds into the lipid bilayer. Here, we show that mutations of the β-tongue did not prevent oligomerization or transmembrane insertion. Instead, β-tongue substitution mutants yielded pores with decreased conductance while a deletion mutation resulted in pores that rapidly closed following membrane association. Our results suggest that the β-tongue may play an essential structural role in stabilizing the open conformation of the transmembrane domain.
The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock
Authors: Hopwood Thomas W. , Hall Sarah , Begley Nicola , Forman Ruth , Brown Sheila , Vonslow Ryan , Saer Ben , Little Matthew C. , Murphy Emma A. , Hurst Rebecca J. , Ray David W. , MacDonald Andrew S. , Brass Andy , Bechtold David A. , Gibbs Julie E. , Loudon Andrew S. , Else Kathryn J. 
Published: February 2018

AbstractResistance to the intestinal parasitic helminth Trichuris muris requires T-helper 2 (TH2) cellular and associated IgG1 responses, with expulsion typically taking up to 4 weeks in mice. Here, we show that the time-of-day of the initial infection affects efficiency of worm expulsion, with strong TH2 bias and early expulsion in morning-infected mice. Conversely, mice infected at the start of the night show delayed resistance to infection, and this is associated with feeding-driven metabolic cues, such that feeding restriction to the day-time in normally nocturnal-feeding mice disrupts parasitic expulsion kinetics. We deleted the circadian regulator BMAL1 in antigen-presenting dendritic cells (DCs) in vivo and found a loss of time-of-day dependency of helminth expulsion. RNAseq analyses revealed that IL-12 responses to worm antigen by circadian-synchronised DCs were dependent on BMAL1. Therefore, we find that circadian machinery in DCs contributes to the TH1/TH2 balance, and that environmental, or genetic perturbation of the DC clock results in altered parasite expulsion kinetics.
Stable N-doped & FeNi-decorated graphene non-precious electrocatalyst for Oxygen Reduction Reaction in Acid Medium
Authors: Barakat Nasser A. M. , El-Deen Ahmed G. , Ghouri Zafar Khan , Al-Meer Saeed 
Published: February 2018

AbstractNiFe nanoparticles-decorated & N-doped graphene is introduced as an effective and stable non-precious electrocatalyst for ORR in the acid medium. Compared to conventional Pt/C electrodes under the same conditions, the proposed nanocatalyst shows closer onset potential and current density. Typically, the observed onset potentials and current densities for the synthesized and Pt/C electrodes are 825 and 910 mV (vs. NHE) and −3.65 and −4.31 mA.cm−2 (at 5 mV.s−1), respectively. However, the most important advantage of the introduced metallic alloy-decorated graphene is its distinct stability in acid medium; the retention in the electrocatalytic performance after 1,000 successive cycles is approximately 98%. This finding is attributed to the high corrosion resistance of the NiFe alloy. The kinetic study indicates that the number of the transferred electrons is 3.46 and 3.89 for the introduced and Pt/C (20 wt%) electrodes, respectively which concludes a high activity for the proposed nanocomposite. The suggested decorated graphene can be synthesized using a multi-thermal method. Typically, nickel acetate, iron acetate, graphene oxide and urea are subjected to MW heating. Then, sintering with melamine in an Argon atmosphere at 750 °C is required to produce the final electrocatalyst. Overall, the introduced NiFe@ N-doped Gr nanocomposite shows remarkable electrochemical activity in the acid medium with long-term stability.
Current-induced magnetic switching with spin-orbit torque in an interlayer-coupled junction with a Ta spacer layer
Authors: Kwak W.-Y. , Kwon J.-H. , Grünberg P. , Han S. H. , Cho B. K. 
Published: February 2018

AbstractSpin-orbit torque has attracted considerable attention as a means to overcome limits of devices based on spin-transfer torque. However, a small magnetic field that is collinear to the current flow must be applied to break symmetry and induce deterministic current-induced magnetization switching. Recently, a junction utilizing interlayer coupling mediated by a Ru spacer layer between two CoFe layers was designed for symmetry breaking and exhibited current-induced magnetization switching without a magnetic field. Here, we demonstrate zero-field current-induced switching of the perpendicular magnetization of a Co layer that is indirectly coupled with a CoFe layer via a Ta spacer. The weak interlayer coupling exhibited by Ta allows the layer thickness to be relatively small (≈0.5 nm), enabling appropriate interlayer coupling to induce spin-orbit torque for current-induced magnetic switching. External magnetic field effects on switching characteristics show that the current switching process is quite stable against external environments.
Gut microbial composition in patients with psoriasis
Authors: Codoñer Francisco M. , Ramírez-Bosca Ana , Climent Eric , Carrión-Gutierrez Miguel , Guerrero Mariano , Pérez-Orquín Jose Manuel , Horga de la Parte José , Genovés Salvador , Ramón Daniel , Navarro-López Vicente , Chenoll Empar 
Published: February 2018

AbstractSince the last 5–10 years the relevance of the gut microbiome on different intestinal illnesses has been revealed. Recent findings indicate the effect of gut microbiome on certain dermatological diseases such as atopic dermatitis. However, data on other skin diseases such as psoriasis are limited. This is the first time attempting to reveal the gut microbiome composition of psoriatic patients with a prospective study including a group of patients with plaque psoriasis, analyzing their gut microbiome and the relationship between the microbiome composition and bacterial translocation. The microbiome of a cohort of 52 psoriatic patients (PASI score ≥6) was obtained by 16s rRNA massive sequencing with MiSeq platform (Illumina inc, San Diego) with an average of 85,000 sequences per sample. The study of the gut microbiome and enterotype shows from the first time a specific “psoriatic core intestinal microbiome” that clearly differs from the one present in healthy population. In addition, those psoriatic patients classified as belonging to enterotype 2 tended to experience more frequent bacterial translocation and higher inflammatory status (71%) than patients with other enterotypes (16% for enterotype 1; and 21% for enterotype 3).
Estimating the nutrient thresholds of a typical tributary in the Liao River basin, Northeast China
Authors: Chen Jiabo , Li Fayun , Wang Yanjie , Kong Yun 
Published: February 2018

AbstractEstimating regional nutrient criteria for streams and rivers is a key step toward protecting river water quality and restoring the health of aquatic ecosystems. Using a multivariable statistical analysis technique, nutrients were identified as the main factor influencing the degradation of the benthic macroinvertebrate community. Three chemical methods (the reference stream distribution approach, all-streams distribution approach and Y-intercept approach) and one biological method (the stress-response approach) were applied to evaluate the nutrient thresholds in the Qing River basin. The reference stream distribution approach and all-streams distribution approach were based on calculating a predetermined percentile of reference streams and all-streams water quality data set, respectively. The Y-intercept approach was based on determining the influence of human activity on water quality by linear regression models. The biological method was based on the response of the benthic macroinvertebrate community structure to changes in water quality. The chemical thresholds were 0.750–1.288 mg/L for total nitrogen (TN) and 0.035–0.046 mg/L for total phosphorus (TP); the biological thresholds were 1.050–1.655 for TN and 0.052–0.101 for TP. The results from the chemical approaches were verified using the biological method, resulting in preliminarily recommended thresholds of 1.000 mg/L TN and 0.040 mg/L TP in the Qing River system.
Bioprocessing strategies for cost-effective large-scale biogenic synthesis of nano-MgO from endophytic Streptomyces coelicolor strain E72 as an anti-multidrug-resistant pathogens agent
Authors: EL-Moslamy Shahira H. 
Published: February 2018

AbstractIn this report, the local nano-MgO synthesizer strain has been isolated from Ocimum sanctum plant and deposited in GenBank as endophytic Streptomyces coelicolor strain E72. Its intracellular metabolic fraction that contains 7.2 μg/μl of carbohydrate, 6.3 g/l of protein and 5.2 nmol/hr/ml of nitrate reductase used to produce multi-surface shaped nano-MgO with diameter ~25 nm. To the best of our knowledge, this is the first report using statistical nanobiotechnological strategies (Plackett -Burman, Box-Behnken and Taguchi experimental designs) to study and evaluate the endophytic S. coelicolor biomass production (123.3 g/l) and extract the highest bioactive metabolites that used for biogenic synthesis of nano-MgO (320 g/l) through exponential sucrose pulses feeding fermentation strategy after 192 hr in semi industrial scale bioreactor (7 L). Purified nano-MgO applied in vitro against multi-drug resistant human pathogens and the large inhibition zone recorded against Shigella flexneri (108 ± 10.53 mm). The average of MICs was recorded as 25 µg/ml that inhibited 90% of the pathogenic living cells and compared with 100 mg/ml ampicilin/sulbactam solution that killed 40% of the same pathogen. These results are expected to gather sufficient knowledge to discover and develop a new cheap and eco-friendly nano-MgO as an extremely strong antimicrobial agent used in biomedical applications.
Visual stimulation-induced mild stress enhances cognitive behavior in cynomolgus monkey
Authors: Woo Dong Ho , Koh Eun Ha , Shin Seung-Hyuk , Yang Young-Su , Choe Jae Chun , Lee C. Justin , Han Su-Cheol 
Published: February 2018

AbstractCortisol is a well-known endogenous glucocorticoid that serves as a stress indicator. It is normally released under stressful condition to warn about imminent danger and thus is critical for survival of the species. However, it is unclear how cortisol relates to cognitive process under physiological condition in high-order primates such as non-human primates (NHP). Here, we report that a slight but significant increase in blood cortisol level by mild stress is positively correlated with the cognitive function in cynomolgus monkey. We stimulated 3 groups of monkeys by viewing consecutive series of pictures of monkeys, pictures of humans, or animation still pictures. We first found that the blood cortisol level was significantly higher during the stimulation session and returned to normal after stimulation session. Among the three types of pictures, the monkeys which were stimulated with monkey pictures showed the most significant increase in cortisol level during stimulation. Furthermore, the monkeys showed significantly enhanced manipulation, suggesting that cortisol affected cognitive processes. Overall, our study demonstrates that visual stimulation both increases blood cortisol and enhances manipulating behavior. Therefore, unlike the common notion that cortisol is a stress indicator, our data supports that a mild increase of cortisol enhances cognition in NHP.
Pathways of cellular internalisation of liposomes delivered siRNA and effects on siRNA engagement with target mRNA and silencing in cancer cells
Authors: Alshehri Abdullah , Grabowska Anna , Stolnik Snow 
Published: February 2018

AbstractDesign of an efficient delivery system is a generally recognised bottleneck in translation of siRNA technology into clinic. Despite research efforts, cellular processes that determine efficiency of siRNA silencing achieved by different delivery formulations remain unclear. Here, we investigated the mechanism(s) of cellular internalisation of a model siRNA-loaded liposome system in a correlation to the engagement of delivered siRNA with its target and consequent silencing by adopting siRNA molecular beacon technology. Probing of cellular internalisation pathways by a panel of pharmacological inhibitors indicated that clathrin-mediated (dynamin-dependent) endocytosis, macropinocytosis (dynamine independent), and cell membrane cholesterol dependent process(es) (clathrin and caveolea-independent) all play a role in the siRNA-liposomes internalization. The inhibition of either of these entry routes was, in general, mirrored by a reduction in the level of siRNA engagement with its target mRNA, as well as in a reduction of the target gene silencing. A dramatic increase in siRNA engagement with its target RNA was observed on disruption of endosomal membrane (by chloroquine), accompanied with an increased silencing. The work thus illustrates that employing molecular beacon siRNA technology one can start to assess the target RNA engagement – a stage between initial cellular internalization and final gene silencing of siRNA delivery systems.
Biodegradation of 17β-estradiol by Bacterial Co-culture Isolated from Manure
Authors: Li Mingtang , Zhao Xingmin , Zhang Xiufang , Wu Di , Leng Su 
Published: February 2018

AbstractAnimal wastes are potential sources of natural and steroidal estrogen hormones into the environment. These hormones can be removed by microorganisms with induced enzymes. Two strains of 17β-estradiol-degrading bacteria (LM1 and LY1) were isolated from animal wastes. Based on biochemical characteristics and 16 S rDNA gene sequences, we identified strains LM1 and LY1 as belonging to the genus of Acinetobacter and Pseudomonas, respectively. Bacterial co-culture containing LM1 and LY1 bacterial strains could rapidly remove approximately 98% of E2 (5 mg L−1) within 7 days. However, strains LM1 and LY1 degraded 77% and 68% of E2 when they were incubated alone, respectively. More than 90% of 17β-estradiol (E2, ≤ 20 mg L−1) could be removed by bacterial co-culture. Low C/N ratio (1:35) was more suitable for bacterial growth and E2 degradation. The optimal pH for bacterial co-culture to degrade E2 ranged from 7.00 to 9.00. Coexisting sodium acetate, glucose and sodium citrate decreased E2 degradation in the first 4 days, but more E2 was removed when they were depleted. The growth of the bacterial co-culture was not significantly decreased by Ni, Pb, Cd or Cu at or below 0.8, 1.2, 1.6 or 0.8 mg L−1, respectively. These data highlight the usefulness of bacterial co-culture in the bioremediation of estrogen-contaminated environments.
Genome-wide analysis revealed that DZNep reduces tubulointerstitial fibrosis via down-regulation of pro-fibrotic genes
Authors: Mimura Imari , Hirakawa Yosuke , Kanki Yasuharu , Nakaki Ryo , Suzuki Yutaka , Tanaka Tetsuhiro , Aburatani Hiroyuki , Nangaku Masaomi 
Published: February 2018

AbstractTubulointerstitial fibrosis has been recently reported to be caused by the collapse of the epigenetic regulation of kidney diseases. We examined whether pharmacological inhibition of histone modification is effective against renal fibrosis. DZNep (3-deazaneplanocin A) was originally developed as an anti-cancer drug to inhibit the repressive histone mark, H3K27me3. We used a model of chronic tubulointerstitial fibrosis induced by unilateral ischaemia/reperfusion and administered DZNep intravenously to the mice for 8 weeks. We found DZNep contributes to the reduction of tubulointerstitial fibrosis. We selected only tubular cells from in vivo samples using laser-capture microdissection because epigenetic regulation is specific to the cell types, and we focused on the changes in the tubular cells. We performed a genome-wide analysis of tubular cells using high-throughput sequencing (RNA-seq) to identify novel epigenetic factors associated with renal fibrosis. We found that pro-fibrotic genes such as COL3A1 (collagen type 3a1) and TIMP2 (tissue inhibitor of metalloproteinase 2) were suppressed by DZNep in vivo. In addition, pro-fibrotic genes such as COL4A1 (collagen type 4a1), TIMP2 and MMP14 were down-regulated by DZNep in vitro. In conclusion, we found that pharmacological epigenetic modification by DZNep decreased the expression levels of fibrogenic genes in tubular cells and inhibited tubulointerstitial fibrosis.
Post-epizootic salamander persistence in a disease-free refugium suggests poor dispersal ability of Batrachochytrium salamandrivorans
Authors: Spitzen - van der Sluijs Annemarieke , Stegen Gwij , Bogaerts Sergé , Canessa Stefano , Steinfartz Sebastian , Janssen Nico , Bosman Wilbert , Pasmans Frank , Martel An 
Published: February 2018

AbstractLack of disease spill-over between adjacent populations has been associated with habitat fragmentation and the absence of population connectivity. We here present a case which describes the absence of the spill-over of the chytrid fungus Batrachochytrium salamandrivorans (Bsal) between two connected subpopulations of fire salamanders (Salamandra salamandra). Based on neutrally evolving microsatellite loci, both subpopulations were shown to form a single genetic cluster, suggesting a shared origin and/or recent gene flow. Alpine newts (Ichthyosaura alpestris) and fire salamanders were found in the landscape matrix between the two sites, which are also connected by a stream and separated by no obvious physical barriers. Performing a laboratory trial using alpine newts, we confirmed that Bsal is unable to disperse autonomously. Vector-mediated dispersal may have been impeded by a combination of sub-optimal connectivity, limited dispersal ability of infected hosts and a lack of suitable dispersers following the rapid, Bsal-driven collapse of susceptible hosts at the source site. Although the exact cause remains unclear, the aggregate evidence suggests that Bsal may be a poorer disperser than previously hypothesized. The lack of Bsal dispersal between neighbouring salamander populations opens perspectives for disease management and stresses the necessity of implementing biosecurity measures preventing human-mediated spread.