bluuebunny/crossref_metadata_2025_split huggingface dataset:
1,3,2,5-Diazadiborinine featuring nucleophilic and electrophilic boron centres
Authors: Wu Di , Kong Lingbing , Li Yongxin , Ganguly Rakesh , Kinjo Rei 
Published: June 2015

AbstractThe seminal discovery in 1865 by Kekulé that benzene nucleus exists with cyclic skeleton is considered to be the beginning of aromatic chemistry. Since then, a myriad of cyclic molecules displaying aromatic property have been synthesized. Meanwhile, borazine (B3N3H6), despite the isostructural and isoelectronic relationships with benzene, exhibits little aromaticity. Herein, we report the synthesis of a 1,3,2,5-diazadiborinine (B2C2N2R6) derivative, a hybrid inorganic/organic benzene, and we present experimental and computational evidence for its aromaticity. In marked contrast to the reactivity of benzene, borazine, and even azaborinines previously reported, 1,3,2,5-diazadiborinine readily forms the adducts with methyl trifluoromethanesulfonate and phenylacetylene without any catalysts. Moreover, 1,3,2,5-diazadiborine activates carbon dioxide giving rise to a bicycle[2,2,2] product, and the binding process was found to be reversible. These results, thus, demonstrate that 1,3,2,5-diazadiborinine features both nucleophilic and electrophilic boron centres, with a formal B(+I)/B(+III) mixed valence system, in the aromatic six-membered B2C2N2 ring.
Short-term weight-centric effects of tea or tea extract in patients with metabolic syndrome: a meta-analysis of randomized controlled trials
Authors: Zhong X , Zhang T , Liu Y , Wei X , Zhang X , Qin Y , Jin Z , Chen Q , Ma X , Wang R , He J 
Published: June 2015

AbstractTo evaluate the weight-centric effect of tea or tea extract in participants with metabolic syndrome (MetS), we performed electronic searches in PubMed, EmBase and the Cochrane Library to identify eligible randomized controlled trials (RCTs) comparing tea or tea extract vs a control group. A direct meta-analysis using random-effects model was conducted to pool the standardized mean difference regarding body mass index (BMI), body weight and waist circumference. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity. A total of five RCTs involving 338 adult individuals were included. Given the high heterogeneity observed in the overall pooled analysis, we separated the included subjects into two subgroups. Ingestion of tea or tea extract significantly reduced BMI (subgroup 1: −1.60, 95% confidence interval (CI), −2.05 to −1.14; subgroup 2: −0.40, 95% CI, −0.69 to −0.12) and body weight (subgroup 1: −4.14, 95% CI, −4.85 to −3.43; subgroup 2: −0.35, 95% CI, −0.68 to −0.02). This meta-analysis suggests that tea or tea extract has favorable weight-centric effects in MetS patients. Additional large RCTs specifically designed to evaluate the effect on anthropometric measurements are needed to further confirm these findings.
Anti-HMGB1 antibody reduces weight gain in mice fed a high-fat diet
Authors: Montes V N , Subramanian S , Goodspeed L , Wang S A , Omer M , Bobik A , Teshigawara K , Nishibori M , Chait A 
Published: June 2015

AbstractInsulin resistance in obesity is believed to be propagated by adipose tissue and liver inflammation. HMGB1 is a multifunctional protein that is pro-inflammatory when released from cells. It has been previously demonstrated that anti-HMGB1 antibody reduces atherosclerotic lesion pro-inflammatory cells and progression of atherosclerosis in a mouse model. To test the potential beneficial role of blocking HMGB1 in adipose tissue and liver inflammation in mice fed an obesogenic diet, we administered anti-HMGB1 antibody to C57Bl/6 mice fed a high (60%)-fat diet. The mice were treated with weekly injections of an anti-HMGB1 antibody or anti-KLH antibody (isotype control) for 16 weeks. Mice that received the anti-HMGB1 antibody gained less weight than the control-treated animals. Anti-HMGB1 treatment also reduced hepatic expression of TNF-alpha and MCP-1, molecules that promote inflammation. However, adipose tissue inflammation, as measured by gene expression analyses and immunohistochemistry, did not differ between the two groups. There also were no differences in glucose or insulin tolerance between the two groups. When feeding mice a high-fat diet, these data suggest that HMGB1 may have a crucial role in weight gain and liver inflammation.
Exploring genetic markers of adult obesity risk in black adolescent South Africans—the Birth to Twenty Cohort
Authors: Pillay V , Crowther N J , Ramsay M , Smith G D , Norris S A , Lombard Z 
Published: June 2015

AbstractTo date more than 90 loci that show an association with body mass index (BMI) and other obesity-related traits, have been discovered through genome-wide association studies. These findings have been widely replicated, mostly in European and Asian populations, but systematic investigation in African cohorts is still lacking. Therefore, the aim of our study was to replicate the association of six single-nucleotide polymorphisms (SNPs) previously linked to BMI, in a South African black adolescent cohort. The SNPs were in or near GNPDA2 (rs10938397), MTCH2 (rs10838738), NEGR1 (rs2568958), SH2B1 (rs7498665), STK33 (rs10769908) and TMEM18 (rs6548238). The SNPs were genotyped in 990 adolescents from the Birth to Twenty study, using an Illumina VeraCode assay, and association with BMI statistically assesed by using PLINK. Three of the SNPs tested were associated with BMI in this African cohort, and showed a consistent (albeit smaller) directional effect to that observed in non-African cohorts. We identified significant association between BMI and rs10938397 (effect allele-G) near GNPDA2 (Padj=0.003), rs7498665 (effect allele-G) in SH2B1 (Padj=0.014) and rs6548238 (effect allele-C) near TMEM18 (Padj=0.030). This data suggests that common genetic variants potentially contributes to obesity risk in diverse population groups.
Specific gut microbiota features and metabolic markers in postmenopausal women with obesity
Authors: Brahe L K , Le Chatelier E , Prifti E , Pons N , Kennedy S , Hansen T , Pedersen O , Astrup A , Ehrlich S D , Larsen L H 
Published: June 2015

Abstract
Background:
Gut microbial gene richness and specific bacterial species are associated with metabolic risk markers in humans, but the impact of host physiology and dietary habits on the link between the gut microbiota and metabolic markers remain unclear. The objective of this study was to identify gut metagenomic markers associated with estimates of insulin resistance, lipid metabolism and inflammation in obesity, and to explore whether the associations between metagenomic and metabolic markers persisted after adjustment for body fat, age and habitual dietary intake.

Methods:
Faecal DNA from 53 women with obesity was analysed through quantitative metagenomic sequencing and analysis, and a systematic search was performed for bacterial genes associated with estimates of insulin resistance, inflammation and lipid metabolism. Subsequently, the correlations between metagenomic species and metabolic markers were tested by linear regression models, with and without covariate adjustment.

Results:
One hundred and fourteen metagenomic species correlated with metabolic markers (P<0.001) including Akkermansia muciniphila, Bilophila wadsworthia, Bifidobacterium longum and Faecalibacterium prausnitzii, but also species not previously associated with metabolic markers including Bacteroides faecis and Dorea longicatena. The majority of the identified correlations between bacterial species and metabolic markers persisted after adjustment for differences in body fat, age and dietary macronutrient composition; however, the negative correlation with insulin resistance observed for B. longum and F. prausnitzii appeared to be modified by the intake of dietary fibre and fat, respectively.

Conclusions:
This study shows that several gut bacterial species are linked to metabolic risk markers in obesity, also after adjustment for potential confounders, such as long-term diet composition. The study supports the use of gut metagenomic markers for metabolic disease prediction and warrants further investigation of causality.
An aberrant nuclear localization of E-cadherin is a potent inhibitor of Wnt/β-catenin-elicited promotion of the cancer stem cell phenotype
Authors: Su Y-J , Chang Y-W , Lin W-H , Liang C-L , Lee J-L 
Published: June 2015

AbstractSeveral studies suggest that Wnt signaling contributes to reprogramming and maintenance of cancer stem cell (CSC) states activated by loss of membranous E-cadherin expression. However, E-cadherin’s exact role in Wnt/β-catenin-mediated promotion of the CSC phenotype remains unclear. Recently, a significant positive correlation has been observed between the expression of nuclear (an aberrant nuclear localization) E-cadherin and β-catenin in gastric and colorectal carcinomas. Here we conducted a series of in-vitro and in-vivo studies to show that the β-catenin/TCF4 interaction was abolished by E-cadherin and was correlated with its nuclear localization, and consequently decreased β-catenin/TCF4 transcriptional activity. Nuclear E-cadherin was a negative regulator of Wnt/β-Catenin-elicited promotion of the CSC phenotype. Using immunohistochemistry on lung cancer tissue microarrays, we found that changes in subcellular location of E-cadherin may be described by tumor grade and stage, suggesting cellular redistribution during lung tumorigenesis. Furthermore, nuclear E-cadherin expression was more significantly inversely correlated with CD133 (a lung CSC marker) expression (P<0.005) than total E-cadherin expression (P<0.05), suggesting that lung cancer as defined by nuclear E-cadherinLow/nuclear β-cateninHigh/CD133High biomarkers has superior prognostic value over total E-cadherinLow/nuclear β-cateninHigh/CD133High.
Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer
Authors: Yang J , Wei J , Wu Y , Wang Z , Guo Y , Lee P , Li X 
Published: June 2015

AbstractAlthough the antitumor role of metformin has been widely reported, the molecular mechanism of this biguanide agent in the inhibition of tumor progression remains unclear. Here, we identified miR-708-5p as a novel target of metformin in prostate cancer cells. Metformin promotes increased expression of miR-708-5p, leading to suppression of endoplasmic reticulum (ER) membrane protein neuronatin (NNAT) expression and subsequently induces apoptosis of prostate cancer cells through the ER stress pathway. Further, miR-708-5p-induced knockdown of NNAT is associated with downregulated intracellular calcium levels and induced malformation of ER-ribosome structure revealed by electronic microscopy. Meanwhile, the unfolded protein response regulator CHOP, p-eIF2α, calreticulin, GRP78 and ATP2A1, all of which are also considered as ER stress markers, are upregulated by metformin and miR-708-5p. Taken together, our findings clearly demonstrate that metformin stimulates increased expression of miR-708-5p to target the NNAT-mediated response to ER stress and apoptosis. This novel regulatory mechanism of metformin in prostate cancer cells not only advances our knowledge on the molecular mechanism of metformin but also provides a promising therapeutic strategy by targeting miR-708-5p and NNAT for prostate cancer treatment.
Differential signaling mechanism for HIV-1 Nef-mediated production of IL-6 and IL-8 in human astrocytes
Authors: Liu Xun , Kumar Anil 
Published: June 2015

AbstractVariety of HIV-1 viral proteins including HIV-1 Nef are known to activate astrocytes and microglia in the brain and cause the release of pro-inflammatory cytokines, which is thought to be one of the mechanisms leading to HIV-1- mediated neurotoxicity. IL-6 and IL-8 have been found in the CSF of patients with HIV-1 associated dementia (HAD), suggesting that they might play important roles in HIV-1 neuropathology. In the present study we examined the effects of HIV-1 Nef on IL-6 and IL-8 induction in astrocytes. The results demonstrate that both IL-6 and IL-8 are significantly induced in HIV-1 Nef-transfected SVGA astrocytes and HIV-1 Nef-treated primary fetal astrocytes. We also determined the molecular mechanisms responsible for the HIV-1 Nef-induced increased IL-6 and IL-8 by using chemical inhibitors and siRNAs against PI3K/Akt/PKC, p38 MAPK, NF-κB, CEBP and AP-1. Our results clearly demonstrate that the PI3K/PKC, p38 MAPK, NF-κB and AP-1 pathways are involved in HIV-1 Nef-induced IL-6 production in astrocytes, while PI3K/PKC and NF-κB pathways are involved in HIV-1 Nef-induced IL-8 production. These results offer new potential targets to develop therapeutic strategy for treatment of HIV-1 associated neurological disorders, prevalent in > 40% of individuals infected with HIV-1.
Novel EPHB4 Receptor Tyrosine Kinase Mutations and Kinomic Pathway Analysis in Lung Cancer
Authors: Ferguson Benjamin D. , Carol Tan Yi-Hung , Kanteti Rajani S. , Liu Ren , Gayed Matthew J. , Vokes Everett E. , Ferguson Mark K. , John Iafrate A. , Gill Parkash S. , Salgia Ravi 
Published: June 2015

AbstractLung cancer outcomes remain poor despite the identification of several potential therapeutic targets. The EPHB4 receptor tyrosine kinase (RTK) has recently emerged as an oncogenic factor in many cancers, including lung cancer. Mutations of EPHB4 in lung cancers have previously been identified, though their significance remains unknown. Here, we report the identification of novel EPHB4 mutations that lead to putative structural alterations as well as increased cellular proliferation and motility. We also conducted a bioinformatic analysis of these mutations to demonstrate that they are mutually exclusive from other common RTK variants in lung cancer, that they correspond to analogous sites of other RTKs’ variations in cancers and that they are predicted to be oncogenic based on biochemical, evolutionary and domain-function constraints. Finally, we show that EPHB4 mutations can induce broad changes in the kinome signature of lung cancer cells. Taken together, these data illuminate the role of EPHB4 in lung cancer and further identify EPHB4 as a potentially important therapeutic target.
Elevation of NO production increases Fe immobilization in the Fe-deficiency roots apoplast by decreasing pectin methylation of cell wall
Authors: Ye Yi Quan , Jin Chong Wei , Fan Shi Kai , Mao Qian Qian , Sun Cheng Liang , Yu Yan , Lin Xian Yong 
Published: June 2015

AbstractCell wall is the major component of root apoplast which is the main reservoir for iron in roots, while nitric oxide (NO) is involved in regulating the synthesis of cell wall. However, whether such regulation could influence the reutilization of iron stored in root apoplast remains unclear. In this study, we observed that iron deficiency elevated NO level in tomato (Solanum lycopersicum) roots. However, application of S-nitrosoglutathione, a NO donor, significantly enhanced iron retention in root apoplast of iron-deficient plants, accompanied with a decrease of iron level in xylem sap. Consequently, S-nitrosoglutathione treatment increased iron concentration in roots, but decreased it in shoots. The opposite was true for the NO scavenging treatment with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO). Interestingly, S-nitrosoglutathione treatment increased pectin methylesterase activity and decreased degree of pectin methylation in root cell wall of both iron-deficient and iron-sufficient plants, which led to an increased iron retention in pectin fraction, thus increasing the binding capacity of iron to the extracted cell wall. Altogether, these results suggested that iron-deficiency-induced elevation of NO increases iron immobilization in root apoplast by decreasing pectin methylation in cell wall.
Differential monocular vs. binocular pupil responses from melanopsin-based photoreception in patients with anterior ischemic optic neuropathy
Authors: Tsika Chrysanthi , Crippa Sylvain V. , Kawasaki Aki 
Published: June 2015

AbstractWe examined the effect of anterior ischemic optic neuropathy (AION) on the activity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupil as proxy. Eighteen patients with AION (10 unilateral, 8 bilateral) and 29 age-matched control subjects underwent chromatic pupillometry. Red and blue light stimuli increasing in 0.5 log steps were presented to each eye independently under conditions of dark and light adaptation. The recorded pupil contraction was plotted against stimulus intensity to generate scotopic and photopic response curves for assessment of synaptically-mediated ipRGC activity. Bright blue light stimuli presented monocularly and binocularly were used for melanopsin activation. The post-stimulus pupil size (PSPS) at the 6th second following stimulus offset was the marker of intrinsic ipRGC activity. Finally, questionnaires were administered to assess the influence of ipRGCs on sleep. The pupil response and PSPS to all monocularly-presented light stimuli were impaired in AION eyes, indicating ipRGC dysfunction. To binocular light stimulation, the PSPS of AION patients was similar to that of controls. There was no difference in the sleep habits of the two groups. Thus after ischemic injury to one or both optic nerves, the summated intrinsic ipRGC activity is preserved when both eyes receive adequate light exposure.
Processes driving nocturnal transpiration and implications for estimating land evapotranspiration
Authors: de Dios Víctor Resco , Roy Jacques , Ferrio Juan Pedro , Alday Josu G. , Landais Damien , Milcu Alexandru , Gessler Arthur 
Published: June 2015

AbstractEvapotranspiration is a major component of the water cycle, yet only daytime transpiration is currently considered in Earth system and agricultural sciences. This contrasts with physiological studies where 25% or more of water losses have been reported to occur occurring overnight at leaf and plant scales. This gap probably arose from limitations in techniques to measure nocturnal water fluxes at ecosystem scales, a gap we bridge here by using lysimeters under controlled environmental conditions. The magnitude of the nocturnal water losses (12–23% of daytime water losses) in row-crop monocultures of bean (annual herb) and cotton (woody shrub) would be globally an order of magnitude higher than documented responses of global evapotranspiration to climate change (51–98 vs. 7–8 mm yr−1). Contrary to daytime responses and to conventional wisdom, nocturnal transpiration was not affected by previous radiation loads or carbon uptake and showed a temporal pattern independent of vapour pressure deficit or temperature, because of endogenous controls on stomatal conductance via circadian regulation. Our results have important implications from large-scale ecosystem modelling to crop production: homeostatic water losses justify simple empirical predictive functions and circadian controls show a fine-tune control that minimizes water loss while potentially increasing posterior carbon uptake.
Analytic descriptions of cylindrical electromagnetic waves in a nonlinear medium
Authors: Xiong Hao , Si Liu-Gang , Yang Xiaoxue , Wu Ying 
Published: June 2015

AbstractA simple but highly efficient approach for dealing with the problem of cylindrical electromagnetic waves propagation in a nonlinear medium is proposed based on an exact solution proposed recently. We derive an analytical explicit formula, which exhibiting rich interesting nonlinear effects, to describe the propagation of any amount of cylindrical electromagnetic waves in a nonlinear medium. The results obtained by using the present method are accurately concordant with the results of using traditional coupled-wave equations. As an example of application, we discuss how a third wave affects the sum- and difference-frequency generation of two waves propagation in the nonlinear medium.
Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development
Authors: Gaynullina Dina , Dweep Harsh , Gloe Torsten , Tarasova Olga S. , Sticht Carsten , Gretz Norbert , Schubert Rudolf 
Published: June 2015

AbstractThe vascular system is characterized by a high degree of plasticity. In particular, functional and structural remodeling of the arterial system takes place during early postnatal development. However, the mechanisms providing such alterations in the rapidly growing organisms are poorly understood, especially for the peripheral vasculature. To explore this, we performed mRNA- and miRNA microarray analysis on muscular type saphenous arteries of young (10–12 days) and adult (2–3 months) rats. Thirty-eight significant pathways (such as oxidative phosphorylation, MAPK signaling, metabolism, cell cycle, DNA replication and focal adhesion) were obtained on differentially regulated genes during postnatal development. Many differentially regulated genes were determined as target- and miRNA-hubs. We also found 92 miRNAs differentially expressed in arteries of young and adult rats. Several significantly regulated pathways were found on these regulated miRNAs. Interestingly, these biological cascades also contain those significantly enriched pathways that were previously identified based on the differently expressed genes. Our data indicate that the expression of many genes involved in the regulation of pathways that are relevant for different functions in arteries may be under the control of miRNAs and these miRNAs regulate the functional and structural remodeling occurring in the vascular system during early postnatal development.
Bursts in discontinuous Aeolian saltation
Authors: Carneiro M. V. , Rasmussen K. R. , Herrmann H. J. 
Published: June 2015

AbstractClose to the onset of Aeolian particle transport through saltation we find in wind tunnel experiments a regime of discontinuous flux characterized by bursts of activity. Scaling laws are observed in the time delay between each burst and in the measurements of the wind fluctuations at the fluid threshold Shields number θc. The time delay between each burst decreases on average with the increase of the Shields number until sand flux becomes continuous. A numerical model for saltation including the wind-entrainment from the turbulent fluctuations can reproduce these observations and gives insight about their origin. We present here also for the first time measurements showing that with feeding it becomes possible to sustain discontinuous flux even below the fluid threshold.
Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias
Authors: Hara Munetsugu , Takahashi Tomoyuki , Mitsumasu Chiaki , Igata Sachiyo , Takano Makoto , Minami Tomoko , Yasukawa Hideo , Okayama Satoko , Nakamura Keiichiro , Okabe Yasunori , Tanaka Eiichiro , Takemura Genzou , Kosai Ken-ichiro , Yamashita Yushiro , Matsuishi Toyojiro 
Published: June 2015

AbstractMethyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure.