bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Florpyrauxifen-benzyl on Herbicide-Resistant and Herbicide-Susceptible Barnyardgrass Accessions
Authors: Miller M. Ryan , Norsworthy Jason K. , Scott Robert C.
Published: November 2017

Florpyrauxifen-benzyl is a new herbicide under development in rice that will provide an alternative mode of action to control barnyardgrass. Multiple greenhouse experiments evaluated florpyrauxifen-benzyl efficacy on barnyardgrass accessions collected in rice fields across Arkansas, and to evaluate its efficacy on herbicide-resistant biotypes. In one experiment, florpyrauxifen-benzyl was applied at the labeled rate of 30 g ai ha−1to 152 barnyardgrass accessions collected from 21 Arkansas counties. Florpyrauxifen-benzyl at 30 g ai ha−1effectively controlled barnyardgrass and subsequently reduced plant height and aboveground biomass. In a dose-response experiment, susceptible-, acetolactate synthase (ALS)-, propanil-, and quinclorac-resistant barnyardgrass biotypes were subjected to nine rates of florpyrauxifen-benzyl ranging from 0 to 120 g ai ha−1. The effective dose required to provide 90% control, plant height reduction, and biomass reduction of the susceptible and resistant biotypes fell below the anticipated labeled rate of 30 g ai ha−1. Based on these results, quinclorac-resistant barnyardgrass as well as other resistant biotypes can be controlled with florpyrauxifen-benzyl at 30 g ai ha−1. Overall, results from these studies indicate that florpyrauxifen-benzyl can be an effective tool for controlling susceptible and currently existing herbicide-resistant barnyardgrass biotypes in rice. Additionally, the unique auxin chemistry of florpyrauxifen-benzyl will introduce an alternative mechanism of action in rice weed control thus acting as an herbicide-resistance management tool.
Eosinophile Gastro-Enteritis (EGE) – Eine diagnostische Herausforderung
Authors: Grandinetti Tanja , Biedermann Luc
Published: November 2017

Zusammenfassung. Die Eosinophile Gastroenteritis (EGE) wurde vor 80 Jahren erstmals von dem Chirurgen Kaijser beschrieben und ist eine chronische entzündliche Erkrankung des Gastrointestinaltraktes [1]. Sie ist histologisch durch den Nachweis eosinophiler Zellinfiltrate von mehr als 20 eosinophilen Granulozyten / HPF in einem oder mehreren Abschnitten des Gastrointestinaltraktes (Oesophagus bis zum Rektum) charakterisiert. Andere Ursachen für eine intestinale Eosinophilie, zum Beispiel Nahrungsmittel-Allergien, Medikamente, parasitäre Infektionen, Hypereosinophilie-Syndrom (HES), Zöliakie sowie chronisch-entzündliche Darmerkrankungen müssen ausgeschlossen werden, bevor die Diagnose gestellt werden kann. Die genaue Häufigkeit der EGE ist unbekannt. EGE kann sowohl bei Kindern als auch Erwachsenen auftreten. Nach der Klassifikation von Klein, welche die Tiefe und die Ausdehnung der eosinophile Granulozyten beschreibt, wird ein mukosaler, submukosaler und serosaler Typ unterschieden [2]. Die EGE stellt eine klinische Herausforderung dar, zumal sie ähnliche klinische Charakteristiken wie funktionelle Störungen, chronische entzündliche Darmerkrankungen oder Zöliakie hat. Ausserdem sind die endoskopischen Befunde oft nicht richtungsweisend und haben deshalb limitierte Aussagekraft. Der arbiträre Cut-Off, von 20 EOS / HPF kann sich als problematisch erweisen, zumal der Gastrointestinaltrakt auch unter physiologischen Bedingungen eosinophile Granulozyten, je nach Segment in verschiedener Dichte, aufweist, was eine Unterscheidung zwischen physiologisch bzw. pathologisch erschweren kann. Die EGE stellt somit nicht nur für den Kliniker, sondern auch für den Pathologen eine diagnostische Herausforderung dar. Die meisten Experten sind sich einig, dass die Erkrankung infolgedessen höchst wahrscheinlich unterdiagnostiziert ist. Die Therapieempfehlungen stützen sich lediglich auf wenige Fallserien, da bisher keine kontrollierten Studien vorliegen. Als Medikamente der ersten Wahl gelten die Kortikosteroide.
Eosinophile Oesophagitis
Authors: Vavricka Stephan R. , Safroneeva Ekaterina , Schoepfer Alain
Published: November 2017

Zusammenfassung. Die eosinophile Oesophagitis (EoE) wurde erstmals 1993 beschrieben. Die Diagnose beruht auf dem Vorhandensein von Symptomen einer oesophagealen Dysfunktion sowie einem dichten eosinophilen Infiltrat in oesophagealen Biopsien, welches trotz einer 8-wöchigen Therapie mit Protonenpumpenhemmern persistiert. Erwachsene Patienten leiden meist an Dysphagie für solide und / oder faserige Speisen, während die Symptomenpräsentation bei Kindern viel variabler ist und Gedeihstörungen, Uebelkeit, Erbrechen, Diarrhoe, Brustschmerzen oder Bauchschmerzen umfassen kann. Der histologische cutoff liegt bei 15 Eosinophilen / high power field. Die EoE tritt häufiger bei Männern als Frauen auf. Der Grossteil der betroffenen Patienten hat begleitende allergische Erkrankungen (Rhinokonjunktivitis, Asthma, Neurodermitis) sowie Speiseallergien. Die EoE wird zunehmend häufig diagnostiziert, aktuell ist von einer Prävalenz von 1 auf 2’000 Einwohner auszugehen. Unbehandelt führt die EoE meist zu oesophagealen Strikturen welche ein relevantes Risiko für eine komplette Speiseobstruktion darstellen. Aktuell gibt es keine EoE-spezifisches Medikament welches durch die Behörden zur EoE-Behandlung zugelassen ist. Therapieoptionen umfassen verschiedene Medikamente (PPI, geschluckte topische Steroide), Eliminationsdiäten, sowie oesphageale Dilatationen im Falle von Strikturen. Diese Zusammenfassung vermittelt aktuelle Kenntisse bzgl. der Epidemiologie, Diagnostik und Therapie der EoE.
Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression
Authors: Lu Jianqin , Liu Xiangsheng , Liao Yu-Pei , Salazar Felix , Sun Bingbing , Jiang Wen , Chang Chong Hyun , Jiang Jinhong , Wang Xiang , Wu Anna M. , Meng Huan , Nel Andre E.
Published: November 2017

While chemotherapy delivery by nanocarriers has modestly improved the survival prospects of pancreatic ductal adenocarcinoma (PDAC), additional engagement of the immune response could be game changing. We demonstrate a nano-enabled approach for accomplishing robust anti-PDAC immunity in syngeneic mice through the induction of immunogenic cell death (ICD) as well as interfering in the immunosuppressive indoleamine 2,3-dioxygenase (IDO) pathway. This is accomplished by conjugating the IDO inhibitor, indoximod (IND), to a phospholipid that allows prodrug self-assembly into nanovesicles or incorporation into a lipid bilayer that encapsulates mesoporous silica nanoparticles (MSNP). The porous MSNP interior allows contemporaneous delivery of the ICD-inducing chemotherapeutic agent, oxaliplatin (OX). The nanovesicles plus free OX or OX/IND-MSNP induce effective innate and adaptive anti-PDAC immunity when used in a vaccination approach, direct tumor injection or intravenous biodistribution to an orthotopic PDAC site. Significant tumor reduction or eradication is accomplishable by recruiting cytotoxic T lymphocytes, concomitant with downregulation of Foxp3+ T cells.
Novel peptide probes to assess the tensional state of fibronectin fibers in cancer
Authors: Arnoldini Simon , Moscaroli Alessandra , Chabria Mamta , Hilbert Manuel , Hertig Samuel , Schibli Roger , Béhé Martin , Vogel Viola
Published: November 2017

Transformations of extracellular matrix (ECM) accompany pathological tissue changes, yet how cell-ECM crosstalk drives these processes remains unknown as adequate tools to probe forces or mechanical strains in tissues are lacking. Here, we introduce a new nanoprobe to assess the mechanical strain of fibronectin (Fn) fibers in tissue, based on the bacterial Fn-binding peptide FnBPA5. FnBPA5 exhibits nM binding affinity to relaxed, but not stretched Fn fibers and is shown to exhibit strain-sensitive ECM binding in cell culture in a comparison with an established Fn-FRET probe. Staining of tumor tissue cryosections shows large regions of relaxed Fn fibers and injection of radiolabeled 111In-FnBPA5 in a prostate cancer mouse model reveals specific accumulation of 111In-FnBPA5 in tumor with prolonged retention compared to other organs. The herein presented approach enables to investigate how Fn fiber strain at the tissue level impacts cell signaling and pathological progression in different diseases.
A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based chemical sensor
Authors: Bryant M. J. , Skelton J. M. , Hatcher L. E. , Stubbs C. , Madrid E. , Pallipurath A. R. , Thomas L. H. , Woodall C. H. , Christensen J. , Fuertes S. , Robinson T. P. , Beavers C. M. , Teat S. J. , Warren M. R. , Pradaux-Caggiano F. , Walsh A. , Marken F. , Carbery D. R. , Parker S. C. , McKeown N. B. , Malpass-Evans R. , Carta M. , Raithby P. R.
Published: November 2017

Selective, robust and cost-effective chemical sensors for detecting small volatile-organic compounds (VOCs) have widespread applications in industry, healthcare and environmental monitoring. Here we design a Pt(II) pincer-type material with selective absorptive and emissive responses to methanol and water. The yellow anhydrous form converts reversibly on a subsecond timescale to a red hydrate in the presence of parts-per-thousand levels of atmospheric water vapour. Exposure to methanol induces a similarly-rapid and reversible colour change to a blue methanol solvate. Stable smart coatings on glass demonstrate robust switching over 104 cycles, and flexible microporous polymer membranes incorporating microcrystals of the complex show identical vapochromic behaviour. The rapid vapochromic response can be rationalised from the crystal structure, and in combination with quantum-chemical modelling, we provide a complete microscopic picture of the switching mechanism. We discuss how this multiscale design approach can be used to obtain new compounds with tailored VOC selectivity and spectral responses.
Vps34 PI 3-kinase inactivation enhances insulin sensitivity through reprogramming of mitochondrial metabolism
Authors: Bilanges Benoit , Alliouachene Samira , Pearce Wayne , Morelli Daniele , Szabadkai Gyorgy , Chung Yuen-Li , Chicanne Gaëtan , Valet Colin , Hill Julia M. , Voshol Peter J. , Collinson Lucy , Peddie Christopher , Ali Khaled , Ghazaly Essam , Rajeeve Vinothini , Trichas Georgios , Srinivas Shankar , Chaussade Claire , Salamon Rachel S. , Backer Jonathan M. , Scudamore Cheryl L. , Whitehead Maria A. , Keaney Erin P. , Murphy Leon O. , Semple Robert K. , Payrastre Bernard , Tooze Sharon A. , Vanhaesebroeck Bart
Published: November 2017

Vps34 PI3K is thought to be the main producer of phosphatidylinositol-3-monophosphate, a lipid that controls intracellular vesicular trafficking. The organismal impact of systemic inhibition of Vps34 kinase activity is not completely understood. Here we show that heterozygous Vps34 kinase-dead mice are healthy and display a robustly enhanced insulin sensitivity and glucose tolerance, phenotypes mimicked by a selective Vps34 inhibitor in wild-type mice. The underlying mechanism of insulin sensitization is multifactorial and not through the canonical insulin/Akt pathway. Vps34 inhibition alters cellular energy metabolism, activating the AMPK pathway in liver and muscle. In liver, Vps34 inactivation mildly dampens autophagy, limiting substrate availability for mitochondrial respiration and reducing gluconeogenesis. In muscle, Vps34 inactivation triggers a metabolic switch from oxidative phosphorylation towards glycolysis and enhanced glucose uptake. Our study identifies Vps34 as a new drug target for insulin resistance in Type-2 diabetes, in which the unmet therapeutic need remains substantial.
A very large-scale microelectrode array for cellular-resolution electrophysiology
Authors: Tsai David , Sawyer Daniel , Bradd Adrian , Yuste Rafael , Shepard Kenneth L.
Published: November 2017

In traditional electrophysiology, spatially inefficient electronics and the need for tissue-to-electrode proximity defy non-invasive interfaces at scales of more than a thousand low noise, simultaneously recording channels. Using compressed sensing concepts and silicon complementary metal-oxide-semiconductors (CMOS), we demonstrate a platform with 65,536 simultaneously recording and stimulating electrodes in which the per-electrode electronics consume an area of 25.5 μm by 25.5 μm. Application of this platform to mouse retinal studies is achieved with a high-performance processing pipeline with a 1 GB/s data rate. The platform records from 65,536 electrodes concurrently with a ~10 µV r.m.s. noise; senses spikes from more than 34,000 electrodes when recording across the entire retina; automatically sorts and classifies greater than 1700 neurons following visual stimulation; and stimulates individual neurons using any number of the 65,536 electrodes while observing spikes over the entire retina. The approaches developed here are applicable to other electrophysiological systems and electrode configurations.
Quantitative measurement of post-concussion syndrome Using Electrovestibulography
Authors: Suleiman Abdelbaset , Lithgow Brian , Dastgheib Zeinab , Mansouri Behzad , Moussavi Zahra
Published: November 2017

In this study, a noninvasive quantitative measure was used to identify short and long term post-concussion syndrome (PCS) both from each other and from healthy control populations. We used Electrovestibulography (EVestG) for detecting neurophysiological PCS consequent to a mild traumatic brain injury (mTBI) in both short-term (N = 8) and long-term (N = 30) (beyond the normal recovery period) symptomatic individuals. Peripheral, spontaneously evoked vestibuloacoustic signals incorporating - and modulated by - brainstem responses were recorded using EVestG, while individuals were stationary (no movement stimulus). Tested were 38 individuals with PCS in comparison to those of 33 age-and-gender-matched healthy controls. The extracted features were based on the shape of the averaged extracted field potentials (FPs) and their detected firing pattern. Linear discriminant analysis classification, incorporating a leave-one-out routine, resulted in (A) an unbiased 84% classification accuracy for separating healthy controls from a mix of long and short-term symptomatology PCS sufferers and (B) a 79% classification accuracy for separating between long and short-term symptomatology PCS sufferers. Comparatively, short-term symptomatology PCS was generally detected as more distal from controls. Based on the results, the EVestG recording shows promise as an assistive objective tool for detecting and monitoring individuals with PCS after normal recovery periods.
Hydrogen gas mediates ascorbic acid accumulation and antioxidant system enhancement in soybean sprouts under UV-A irradiation
Authors: Jia Li , Tian Jiyuan , Wei Shengjun , Zhang Xiaoyan , Xu Xuan , Shen Zhenguo , Shen Wenbiao , Cui Jin
Published: November 2017

The soybean sprout is a nutritious and delicious vegetable that is rich in ascorbic acid (AsA). Hydrogen gas (H2) may have potential applications in the vegetable processing industry. To investigate whether H2 is involved in the regulation of soybean sprouts AsA biosynthesis under UV irradiation, we set 4 different treatments: white light(W), W+HRW, UV-A and UV-A+HRW. The results showed that H2 significantly blocked the UV-A-induced accumulation of ROS, decreased TBARS content and enhanced SOD and APX activity in soybean sprouts. We also observed that the UV-A induced accumulation of AsA was enhanced more intensely when co-treated with HRW. Molecular analyses showed that UV-A+HRW significantly up-regulated AsA biosynthesis and recycling genes compared to UV-A in soybean sprouts. These data demonstrate that the H2 positively regulates soybean sprouts AsA accumulation under UV-A and that this effect is mediated via the up-regulation of AsA biosynthesis and recycling genes.
Estimation of the molecular vibration of gases using electron microscopy
Authors: Katsukura Hirotaka , Miyata Tomohiro , Shirai Manabu , Matsumoto Hiroaki , Mizoguchi Teruyasu
Published: November 2017

Reactions in gaseous phases and at gas/solid interfaces are widely used in industry. Understanding of the reaction mechanism, namely where, when, and how these gaseous reactions proceed, is crucial for the development of further efficient reaction systems. To achieve such an understanding, it is indispensable to grasp the dynamic behavior of the gaseous molecules at the active site of the chemical reaction. However, estimation of the dynamic behavior of gaseous molecules in specific nanometer-scale regions is always accompanied by great difficulties. Here, we propose a method for the identification of the dynamic behavior of gaseous molecules using an electron spectroscopy observed with a transmission electron microscope in combination with theoretical calculations. We found that our method can successfully identify the dynamic behavior of some gaseous molecules, such as O2 and CH4, and the sensitivity of the method is affected by the rigidity of the molecule. The method has potential to measure the local temperature of gaseous molecules as well. The knowledge obtained from this technique is fundamental for further high resolution studies of gaseous reactions using electron microscopy.
FAD104, a regulator of adipogenesis, is a novel suppressor of TGF-β–mediated EMT in cervical cancer cells
Authors: Goto Motoharu , Osada Shigehiro , Imagawa Masayoshi , Nishizuka Makoto
Published: November 2017

Epithelial-to-mesenchymal transition (EMT) is a biological process in which epithelial cells translate into a mesenchymal phenotype with invasive capacities, contributing to tumour progression, metastasis, and the acquisition of chemotherapy resistance. To identify new therapeutic targets for cancers, it is important to clarify the molecular mechanism of induction of EMT. We have previously reported that fad104, a positive regulator of adipocyte differentiation, suppressed the invasion and metastasis of melanoma and breast cancer cells. In this study, we showed that FAD104 functions as a novel suppressor of transforming growth factor-β (TGF-β)–mediated EMT in cervical cancer cells. Expression of FAD104 is upregulated during TGF-β–mediated EMT in human cervical cancer HeLa cells. Reduction of fad104 expression enhanced TGF-β–mediated EMT and migration in HeLa cells. Conversely, overexpression of FAD104 suppressed TGF-β–induced EMT. In addition, we showed that FAD104 negatively regulated phosphorylation of Smad2 and Smad3 but positively regulated phosphorylation of Smad1/5/8 via treatment with TGF-β. These findings demonstrate that FAD104 is a novel suppressor of TGF-β signalling and represses TGF-β–mediated EMT in cervical cancer cells.
In silico-based screen synergistic drug combinations from herb medicines: a case using Cistanche tubulosa
Authors: Liu Jianling , Zhu Jinglin , Xue Jun , Qin Zonghui , Shen Fengxia , Liu Jingjing , Chen Xuetong , Li Xiaogang , Wu Ziyin , Xiao Wei , Zheng Chunli , Wang Yonghua
Published: November 2017

Neuroinflammation is characterized by the elaborated inflammatory response repertoire of central nervous system tissue. The limitations of the current treatments for neuroinflammation are well-known side effects in the clinical trials of monotherapy. Drug combination therapies are promising strategies to overcome the compensatory mechanisms and off-target effects. However, discovery of synergistic drug combinations from herb medicines is rare. Encouraged by the successfully applied cases we move on to investigate the effective drug combinations based on system pharmacology among compounds from Cistanche tubulosa (SCHENK) R. WIGHT. Firstly, 63 potential bioactive compounds, the related 133 direct and indirect targets are screened out by Drug-likeness evaluation combined with drug targeting process. Secondly, Compound-Target network is built to acquire the data set for predicting drug combinations. We list the top 10 drug combinations which are employed by the algorithm Probability Ensemble Approach (PEA), and Compound-Target-Pathway network is then constructed by the 12 compounds of the combinations, targets, and pathways to unearth the corresponding pharmacological actions. Finally, an integrating pathway approach is developed to elucidate the therapeutic effects of the herb in different pathological features-relevant biological processes. Overall, the method may provide a productive avenue for developing drug combination therapeutics.
Functional interplay between the transcription factors USF1 and PDX-1 and protein kinase CK2 in pancreatic β-cells
Authors: Spohrer Sarah , Groß Rebecca , Nalbach Lisa , Schwind Lisa , Stumpf Heike , Menger Michael D. , Ampofo Emmanuel , Montenarh Mathias , Götz Claudia
Published: November 2017

Glucose homeostasis is regulated by insulin, which is produced in the β-cells of the pancreas. The synthesis of insulin is controlled by several transcription factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as substrates for protein kinase CK2. Here, we have analysed the interplay of PDX-1, USF1 and CK2 in the regulation of PDX-1 gene transcription. We found that the PDX-1 promoter is dose-dependently transactivated by PDX-1 and transrepressed by USF1. With increasing glucose concentrations the transrepression of the PDX-1 promoter by USF1 is successively abrogated. PDX-1 binding to its own promoter was not influenced by glucose, whereas USF1 binding to the PDX-1 promoter was reduced. The same effect was observed after inhibition of the protein kinase activity by three different inhibitors or by using a phospho-mutant of USF1. Moreover, phosphorylation of USF1 by CK2 seems to strengthen the interaction between USF1 and PDX-1. Thus, CK2 is a negative regulator of the USF1-dependent PDX-1 transcription. Moreover, upon inhibition of CK2 in primary islets, insulin expression as well as insulin secretion were enhanced without affecting the viability of the cells. Therefore, inhibition of CK2 activity may be a promising approach to stimulate insulin production in pancreatic β-cells.
Systemic clearance and brain distribution of carbazole-based cyanine compounds as Alzheimer’s disease drug candidates
Authors: Zhou Wei , Hu Xiaohui , Tam Kin Yip
Published: November 2017

SLM and SLOH, two analogues of carbazole-based cyanine compounds, have been shown to inhibit β-amyloid peptide aggregation in vitro and in Alzheimer’s disease model mice, which could be potentially developed into drugs for disease treatment. To pave the way for further pharmacokinetics-pharmacodynamics study, we set to investigate these compounds’ systemic clearance pathways and their brain exposure. We found that they generally exhibited relatively low plasma clearance which comprised of hepatic clearance and biliary clearance. Phase I oxidative metabolites for SLM and for SLOH upon microsomes incubation were identified, and the metabolism by CYP3A4 were found to be the major (>70%) hepatic clearance pathway, while the efflux by P-gp and BCRP located in the canalicular membrane of hepatocytes led to high biliary clearance. The permeation of SLM and SLOH through the brain endothelium was affected by the efflux transporters (P-gp and BCRP) and influx transporter (OATP2B1). The unbound interstitial fluid to plasma ratio (Kpuu,brain) was 8.10 for SLOH and 11.0 for SLM, which favored brain entry and were several folds higher than that in wild-type mice. Taken together, these carbazole compounds displayed low plasma clearance and high brain permeability, which entitle further development.
The Relationship between Secondary Forest and Environmental Factors in the Southern Taihang Mountains
Authors: Zhao Hui , Wang Qi-Rui , Fan Wei , Song Guo-Hua
Published: November 2017

It is important to understand the effects of environmental factors on secondary forest assembly for effective afforestation and vegetation restoration. We studied 24 20 m × 20 m quadrats of natural secondary forest in the southern Taihang Mountains. Canonical correspondence analysis (CCA) and two-way indicator hydrocarbon analysis were used to analyse the relationship between community vegetation and environmental factors. The CCA showed that 13 terrain and soil variables shared 68.17% of the total variance. The principal environmental variables, based on the most parsimonious CCA model, were (in order) elevation, soil total N, soil gravel content, slope, soil electrical conductivity, and pH. Samples were clustered into four forest types, with forest diversity affected by elevation, nutrients, and water gradients. Topographical variables affected forest assembly more than soil variables. Species diversity was evaluated using the Shannon–Wiener, Simpson’s diversity, and Pielou’s evenness indexes. The environmental factors that affected species distribution had different effects on species diversity. The vegetation-environment relationship in the southern region was different than the central region of the Taihang Mountains, and vegetation restoration was at an early stage. The terrain of the southern region, especially elevation and slope, should be considered for vegetation restoration and conservation.
Novel Common Variants Associated with Obesity and Type 2 Diabetes Detected Using a cFDR Method
Authors: Zhang Qiang , Wu Ke-Hao , He Jing-Yang , Zeng Yong , Greenbaum Jonathan , Xia Xin , Liu Hui-Min , Lv Wan-Qiang , Lin Xu , Zhang Wei-Dong , Xi Yuan-Lin , Shi Xue-Zhong , Sun Chang-Qing , Deng Hong-Wen
Published: November 2017

Genome-wide association studies (GWASs) have been performed extensively in diverse populations to identify single nucleotide polymorphisms (SNPs) associated with complex diseases or traits. However, to date, the SNPs identified fail to explain a large proportion of the variance of the traits/diseases. GWASs on type 2 diabetes (T2D) and obesity are generally focused on individual traits independently, and genetic intercommunity (common genetic contributions or the product of over correlated phenotypic world) between them are largely unknown, despite extensive data showing that these two phenotypes share both genetic and environmental risk factors. Here, we applied a recently developed genetic pleiotropic conditional false discovery rate (cFDR) approach to discover novel loci associated with BMI and T2D by incorporating the summary statistics from existing GWASs of these two traits. Conditional Q-Q and fold enrichment plots were used to visually demonstrate the strength of pleiotropic enrichment. Adopting a cFDR nominal significance level of 0.05, 287 loci were identified for BMI and 75 loci for T2D, 23 of which for both traits. By incorporating related traits into a conditional analysis framework, we observed significant pleiotropic enrichment between obesity and T2D. These findings may provide novel insights into the etiology of obesity and T2D, individually and jointly.
CSA13 inhibits colitis-associated intestinal fibrosis via a formyl peptide receptor like-1 mediated HMG-CoA reductase pathway
Authors: Xu Chunlan , Ghali Sally , Wang Jiani , Shih David Q. , Ortiz Christina , Mussatto Caroline C. , Lee Elaine C. , Tran Diana H. , Jacobs Jonathan P. , Lagishetty Venu , Fleshner Phillip , Robbins Lori , Vu Michelle , Hing Tressia C. , McGovern Dermot P. B , Koon Hon Wai
Published: November 2017

Many Crohn’s disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature and antimicrobial function with antimicrobial peptide cathelicidin. As many functions of cathelicidin are mediated through formyl peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated intestinal fibrosis mouse model with the administration of CSA13 was used. Colonic FPRL1 mRNA expression was positively correlated with the histology scores of inflammatory bowel disease patients. In CD patients, colonic FPRL1 mRNA was positively correlated with intestinal stricture. CSA13 administration ameliorated intestinal fibrosis without influencing intestinal microbiota. Inhibition of FPRL1, but not suppression of intestinal microbiota, reversed these protective effects of CSA13. Metabolomic analysis indicated increased fecal mevalonate levels in the TNBS-treated mice, which were reduced by the CSA13 administration. CSA13 inhibited colonic HMG-CoA reductase activity in an FPRL1-dependent manner. Mevalonate reversed the anti-fibrogenic effect of CSA13. The increased colonic FPRL1 expression is associated with severe mucosal disease activity and intestinal stricture. CSA13 inhibits intestinal fibrosis via FPRL1-dependent modulation of HMG-CoA reductase pathway.
Comparison of graphical optimization or IPSA for improving brachytheraphy plans associated with inadequate target coverage for cervical cancer
Authors: Liu ZhiJie , Liang HuanQing , Wang Xiao , Yang HaiMing , Deng Ye , Luo TingJun , Yang ChaoFeng , Lu Min , Fu QingGuo , Zhu XiaoDong
Published: November 2017

Many studies have reported that inverse planning by simulated annealing (IPSA) can improve the quality of brachytherapy plans, and we wanted to examine whether IPSA could improve cervical cancer brachytherapy plans giving D90 < 6 Gy (with 7 Gy per fraction) at our institution. Various IPSA plans involving the tandem and ovoid applicators were developed for 30 consecutive cervical cancer patients on the basis of computed tomography: IPSA1, with a constraint on the maximum dose in the target volume; IPSA1-0, identical to IPSA1 but without a dwell-time deviation constraint; IPSA2, without a constraint on the maximum dose; and IPSA2-0, identical to IPSA2 but without a dwell-time deviation constraint. IPSA2 achieved similar results as graphical optimization, and none of the other IPSA plans was significantly better than graphical optimization. Therefore, other approaches, such as combining interstitial and intracavitary brachytherapy, may be more appropriate for improving the quality of brachytherapy plans associated with inadequate target coverage.
Regulation of human and mouse telomerase genes by genomic contexts and transcription factors during embryonic stem cell differentiation
Authors: Cheng De , Wang Shuwen , Jia Wenwen , Zhao Yuanjun , Zhang Fan , Kang Jiuhong , Zhu Jiyue
Published: November 2017

Differential regulation of telomerase reverse transcriptase (TERT) genes contribute to distinct aging and tumorigenic processes in humans and mice. To study TERT regulation, we generated mouse embryonic stem cell (ESC) lines containing single-copy bacterial artificial chromosome (BAC) reporters, covering hTERT and mTERT genes and their neighboring loci, via recombinase-mediated BAC targeting. ESC lines with chimeric BACs, in which two TERT promoters were swapped, were also generated. Using these chromatinized BACs, we showed that hTERT silencing during differentiation to embryoid bodies (EBs) and to fibroblast-like cells was driven by the human-specific genomic context and accompanied by increases of repressive epigenetic marks, H3K9me3 and H3K27me3, near its promoter. Conversely, the mouse genomic context did not repress TERT transcription until late during differentiation. The hTERT promoter was more active than its mouse counterpart when compared in the same genomic contexts. Mutations of E-box and E2F consensus sites at the promoter had little effect on hTERT transcription in ESCs. However, the mutant promoters were rapidly silenced upon EB differentiation, indicating that transcription factors (TFs) bound to these sites were critical in maintaining hTERT transcription during differentiation. Together, our study revealed a dynamic hTERT regulation by chromatin environment and promoter-bound TFs during ESC differentiation.
Quantitative profiling of carbonyl metabolites directly in crude biological extracts using chemoselective tagging and nanoESI-FTMS
Authors: Deng Pan , Higashi Richard M. , Lane Andrew N. , Bruntz Ronald C. , Sun Ramon C. , Ramakrishnam Raju Mandapati V. , Nantz Michael H. , Qi Zhen , Fan Teresa W.-M.
Published: November 2017

The investigators report a dramatically improved chemoselective analysis for carbonyls in crude biological extracts by turning to a catalyst and freezing conditions for derivatization.
Biofilm dispersal using nitric oxide loaded nanoparticles fabricated by photo-PISA: influence of morphology
Authors: Sadrearhami Zahra , Yeow Jonathan , Nguyen Thuy-Khanh , Ho Kitty K. K. , Kumar Naresh , Boyer Cyrille
Published: November 2017

The morphology of nitric oxide loaded polymeric nanoparticles is a significant parameter that influence the nitric oxide release and dispersal of bacterial biofilms.
Hierarchical CaCO3 particles self-assembled from metastable vaterite and stable calcite during the decomposition of Ca(HCO3)2
Authors: Jiang Jiuxin , Chen Chuanjie , Xiao Bowen , Bai Zhenlong , Jiang Chipeng , Yang Cancan , Wu Yue , Wang Xuelian
Published: November 2017

When Ca(HCO3)2 solution is put at 80 °C, ACC initially formed grow into calcite, aragonite and vaterite particles. The trunk of snow-shaped particles are self-assembled from hexagonal vaterite particles by one or more steps, followed by the filling in the pores of snow-shaped particles by small crystals.
Design of a catalyst through Fe doping of the boron cage B10H14for CO2hydrogenation and investigation of the catalytic character of iron hydride (Fe–H)
Authors: Qian Lei , Ma Kai-Yang , Zhou Zhong-Jun , Ma Fang
Published: November 2017

The Fe–H in Fe doped decahydroborate plays an important role in CO2hydrogenation.
Conformational disorder and solvation properties of the key-residues of a protein in water–ethanol mixed solutions
Authors: Mohanta Dayanidhi , Santra Santanu , Jana Madhurima
Published: November 2017

Restricted structural relaxation of the key-residue–water and key-residue–ethanol hydrogen bonds and the formation of a strong long-lived hydrogen bonding environment in the unfolded protein nourishes the key-residues to trigger unfolding.
UV photodissociation dynamics of CHI2Cl and its role as a photolytic precursor for a chlorinated Criegee intermediate
Authors: Kapnas Kara M. , Toulson Benjamin W. , Foreman Elizabeth S. , Block Sarah A. , Hill J. Grant , Murray Craig
Published: November 2017

Photolysis of geminal diiodoalkanes in the presence of molecular oxygen has become an established route to the laboratory production of several Criegee intermediates, and such compounds also have marine sources.
The σ-hole revisited
Authors: Politzer Peter , Murray Jane S. , Clark Timothy , Resnati Giuseppe
Published: November 2017

A covalently-bonded atom typically has a region of lower electronic density, a “σ-hole,” on the side of the atom opposite to the bond, approximately along its extension. There is often a positive electrostatic potential (strongest shown in red) associated with a σ-hole, although it may deviate from the extension of the bond.
Role of surface oxidation on the size dependent mechanical properties of nickel nanowires: a ReaxFF molecular dynamics study
Authors: Aral Gurcan , Islam Md Mahbubul , van Duin Adri C. T.
Published: November 2017

Highly reactive metallic nickel (Ni) is readily oxidized by oxygen (O2) molecules even at low temperatures.
External oxidant-free cross-coupling: electrochemically induced aromatic C–H phosphonation of azoles with dialkyl-H-phosphonates under silver catalysis
Authors: Yurko E. O. , Gryaznova T. V. , Kholin K. V. , Khrizanforova V. V. , Budnikova Y. H.
Published: November 2017

A convenient external oxidant-free method of azole derivatives phosphorylation by dialkyl-H-phosphonates through electrochemical catalytic oxidation in the presence of silver salts (1%) is proposed.
Hydrothermal encapsulation of VO2(A) nanorods in amorphous carbon by carbonization of glucose for energy storage devices
Authors: Zheng Jiqi , Zhang Yifu , Wang Qiushi , Jiang Hanmei , Liu Yanyan , Lv Tianming , Meng Changgong
Published: November 2017

This work developed a new route to synthesize VO2(A)@C composites and explore their application as a promising material for SCs.
Template-free synthesis of interconnected carbon nanosheets via cross-linking coupled with annealing for high-efficiency triiodide reduction
Authors: Li Mingyu , Yu Chang , Hu Chao , Zhao Changtai , Zhang Mengdi , Ding Yiwang , Wang Xiuna , Qiu Jieshan
Published: November 2017

A facile and template-free strategy was developed for the synthesis of interconnected carbon nanosheets with a power conversion efficiency of 8.71% as a counter electrode, outperforming a Pt reference (7.24%).
Unravelling the energy transfer of Er3+-self-sensitized upconversion in Er3+–Yb3+–Er3+clustered core@shell nanoparticles
Authors: Huang Bolong , Sun Mingzi , Dougherty Alan William , Dong Hao , Xu Yue-Jiao , Sun Ling-Dong , Yan Chun-Hua
Published: November 2017

The interplay on enhancing and quenching effects between Er3+and Yb3+dopant clusters in self-sensitized core@shell nanoparticles is studied.
Bacterial self-defense antibiotics release from organic–inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties
Authors: Xu Qingwen , Li Xi , Jin Yingying , Sun Lin , Ding Xiaoxu , Liang Lin , Wang Lei , Nan Kaihui , Ji Jian , Chen Hao , Wang Bailiang
Published: November 2017

Implant-associated bacterial infections pose serious medical and financial issues due to the colonization and proliferation of pathogens on the surface of the implant.
Hybrid magneto-plasmonic liposomes for multimodal image-guided and brain-targeted HIV treatment
Authors: Tomitaka Asahi , Arami Hamed , Huang Zaohua , Raymond Andrea , Rodriguez Elizette , Cai Yong , Febo Marcelo , Takemura Yasushi , Nair Madhavan
Published: November 2017

Magneto-plasmonic liposomes were developed for image-guided drug delivery, and showed multimodal imaging, enhanced BBB transmigration, and reduction of viral replication.
NiMn2O4 spinel binary nanostructure decorated on three-dimensional reduced graphene oxide hydrogel for bifunctional materials in non-enzymatic glucose sensor
Authors: Ngo Yen-Linh Thi , Sui Lijun , Ahn Wei , Chung Jin Suk , Hur Seung Hyun
Published: November 2017

Nickel–manganese spinel oxide (NiMn2O4) was hybridized with reduced graphene oxide hydrogel (rGOH) via a facile solvothermal process and a highly porous three-dimensional (3D) structure was constructed.
Automated glycan assembly of galactosylated xyloglucan oligosaccharides and their recognition by plant cell wall glycan-directed antibodies
Authors: Dallabernardina Pietro , Ruprecht Colin , Smith Peter J. , Hahn Michael G. , Urbanowicz Breeanna R. , Pfrengle Fabian
Published: November 2017

Automated glycan assembly enabled the synthesis of galactosylated xyloglucan oligosaccharides from the plant cell wall. The synthetic glycans were differentially recognized by a number of xyloglucan-directed antibodies.
The influence of convective blueshift on radial velocities of F, G, and K stars
Authors: Bauer F. F. , Reiners A. , Beeck B. , Jeffers S. V.
Published: November 2017

Context.Apparent radial velocity (RV) signals induced by stellar surface features such as spots and plages can result in a false planet detection or hide the presence of an orbiting planet. Our ability to detect rocky exoplanets is currently limited by our understanding of such stellar signals.

Aims.We model RV variations caused by active regions on the stellar surface of typical exoplanet-hosting stars of spectral type F, G, and K. We aim to understand how the stellar magnetic field strength, convective blueshift, and spot temperatures can influence RV signals caused by active regions.

Methods.We use magneto-hydrodynamic (MHD) simulations for stars with spectral types F3V, a G2V, and a K5V. We quantify the impact of the magnetic field strength inside active regions on the RV measurement using the magnetic and non-magnetic FeI lines at 6165 Å and 6173 Å. We also quantify the impact of spot temperature and convective blueshift on the measured RV values.

Results.Increasing the magnetic field strength increases the efficiency to suppress convection in active regions which results in an asymmetry between red- and blueshifted parts of the RV curves. A stronger suppression of convection also leads to an observed increase in RV amplitude for stronger magnetic fields. The MHD simulations predict convective motions to be faster in hotter stars. The suppression of faster convection leads to a stronger RV amplitude increase in hotter stars when the magnetic field is increased. While suppression of convection increases the asymmetry in RV curves,c a decreasing spot temperature counteracts this effect. When using observed temperatures for dark spots in our simulations we find that convective blueshift effects are negligible.
Insights into the Cobalt-Catalyzed Three-Component Coupling of Mixed Aromatic Organozinc Species, Carbonyl Compounds or Imines and Michael Acceptors: Synthetic and Mechanistic Aspects
Authors: Le Gall Erwan , Paul Jérôme , Presset Marc , Léonel Eric , Retailleau Pascal
Published: November 2017

The first examples of cobalt-catalyzed multicomponent couplings of mixed aromatic arylzinc reagents with Michael acceptors and carbonyl compounds or imines is described. The reaction system employs a cobalt(II)-2,2′-bipyridine or a cobalt(II)-1,10-phenanthroline complex as a catalyst for both organozinc generation and subsequent multicomponent assembly by formal Michael addition/aldol coupling or Mannich reaction. This study brings new insights into the synthetic scope and mechanism of the reaction.
A short telephone-call reminder improves bowel preparation, quality indicators and patient satisfaction with first colonoscopy
Authors: Gálvez Marisol , Zarate Angel , Espino Hector , Higuera-de la Tijera Fátima , Awad Richard , Camacho Santiago
Published: November 2017

Background and study aims Addition of a reminder program to conventional indications improves colonoscopy. The aim of this study was to evaluate the effectiveness of a short telephone call reminder (STCR) on a patient’s first colonoscopy.

Patients and methods One day before colonoscopy, we made a STCR of < 10 minutes to 141 randomly selected patients of 258 recruited. The STCRs informed patients about the procedure date, indications for taking laxatives, and dietetic requirements. Questions were clarified only when patients asked directly. We evaluated bowel preparation, quality indicators, and patient satisfaction. Data were expressed as mean ± SD and percentages. Statistical differences were evaluated by Student’s t and Chi squared tests; alpha = 0.05. All authors had access to the study data and reviewed and approved the final manuscript.

Results The STCR group had better bowel preparation which was demonstrated by higher completion frequency (97.16 % vs. 82.05 %), in less time (4.52 ± 3.06 vs. 5.38 ± 3.03 hours) intake of laxative, and higher Boston’s scale (7.66 ± 2.42 vs. 5.2 ± 1.65). Quality indicators of colonoscopy were better in patients that received a STCR [cecal intubation rate: 100.00 % vs. 87.18 %; polyp detection: 42.55 % vs. 9.4 %; and cecal arrival time (min): 12.09 ± 3.62 vs. 15.09 ± 5.02]. STCR patients were more satisfied (97.87 % vs. 55.56 %) and would repeat colonoscopy (21.99 % vs. 11.11 %).

Conclusions A simple additional step such as a STCR improves quality of bowel preparation, quality indicators, and satisfaction of patients undergoing their first colonoscopy. Clinical trial registry in Mexico City General Hospital: DI/16/107/3/108.
Three-dimensional imaging of absolute blood flow velocity and blood vessel position under low blood flow velocity based on Doppler signal information included in scattered light from red blood cells
Authors: Kyoden Tomoaki , Akiguchi Shunsuke , Tajiri Tomoki , Andoh Tsugunobu , Hachiga Tadashi
Published: November 2017

The development of a system for in vivo visualization of occluded distal blood vessels for diabetic patients is the main target of our research. We herein describe two-beam multipoint laser Doppler velocimetry (MLDV), which measures the instantaneous multipoint flow velocity and can be used to observe the blood flow velocity in peripheral blood vessels. By including a motorized stage to shift the measurement points horizontally and in the depth direction while measuring the velocity, the path of the blood vessel in the skin could be observed using blood flow velocity in three-dimensional space. The relationship of the signal power density between the blood vessel and the surrounding tissues was shown and helped us identify the position of the blood vessel. Two-beam MLDV can be used to simultaneously determine the absolute blood flow velocity distribution and identify the blood vessel position in skin.
Highly accelerated lifetime testing of potassium sodium niobate thin films
Authors: Zhu Wanlin , Akkopru-Akgun Betul , Trolier-McKinstry Susan
Published: November 2017

Highly accelerated lifetime tests of 2 and 3 μm thick potassium sodium niobate [(K0.5, Na0.5)NbO3, KNN] films with different thicknesses were measured under electric fields ranging from 160 to 350 kV/cm and temperatures ranging from 90 to 210 °C. The medium time to failure (t50) was determined from a lognormal distribution plot of failure times of up to 22 electrodes per measurement condition. The activation energy (Ea) for failure was 0.74 ± 0.04 eV and 0.92 ± 0.05 eV for the 2 μm and 3 μm KNN films, respectively. The voltage acceleration factor was 3.5 ± 0.34 for the 3 μm film. But the electric field dependence of t50 for the 2 μm film showed two regions with similar N, 6.67 and 6.94 ± 0.23, respectively. Energy-dispersive X-ray spectroscopy was employed to investigate the Na+ and K+ ion distributions in KNN films.
Large amplitude ion-acoustic solitons in warm negative ion plasmas with superthermal electrons
Authors: Kumar Kishan , Mishra M. K.
Published: November 2017

Large amplitude ion-acoustic solitons are investigated in a plasma consisting of warm adiabatic positive and negative-ions and hot superthermal electrons having kappa distributions. Using Pseudo-potential method an energy integral equation is derived for the system. The latter is analysed to examine the existence regions of the solitary waves. It is found that negative ion concentration (α), spectral index (k) and ionic temperature ratio (σ1 or σ2) significantly influence the characteristic of the solitons. Our numerical analysis shows that the system also supports rarefactive solitons for some selected set of plasma parameters. It is also found that large amplitude ion-acoustic compressive and rarefactive solitons exist simultaneously for the same values of plasma parameters. Further an increase in the superthermality (i.e. decreasing the value of spectral index k) leads to shrinking the existing domain of the large amplitude ion-acoustic solitons. The amplitude of the compressive/rarefactive solitons increases with the increase in negative ion concentration (α). Whereas, on increasing ionic temperature ratio (σ1 or σ2) the amplitude of the compressive/rarefactive soliton decreases. The effect of negative-ion concentration (α), temperature ratio of two ion species (σ1 and σ2), Mach number (M) and spectral index (k) on the characteristics of solitons are discussed in detail. The results of the present investigation may be helpful to understand the nonlinear ion-acoustic solitary waves in space plasma and laboratory plasmas, where two distinct groups of ions and non-Boltzmann distribution electrons are present.