bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED ARTICLE: A Zinc Morpholine Complex Prevents HCl/Ethanol-Induced Gastric Ulcers in a Rat Model
Authors: Salama Suzy M. , Gwaram Nura Suleiman , AlRashdi Ahmed S. , Khalifa Shaden A. M. , Abdulla Mahmood A. , Ali Hapipah M. , El-Seedi Hesham R. 
Published: July 2016

AbstractZinc is a naturally occurring element with roles in wound healing and rescuing tissue integrity, particularly in the gastrointestinal system, where it can be detected in the mucosal and submucosal layers. Zinc chelates are known to have beneficial effects on the gastrointestinal mucosa and in cases of gastric ulcer. We synthesized complexes of zinc featuring a heterocyclic amine binding amino acids then investigated their ability to enhance the gastric self-repair. Zinc-morpholine complex, Zn(L)SCN, namely showed strong free-radical scavenging, promotion of the DNA and RNA polymerases reconstruction and suppression of cell damage. The complex’s mode of action is proposed to involve hydrogen bond formation via its bis(thiocyanato-k)zinc moiety. Zn(L)SCN complex had potent effects on gastric enzymatic activity both in vitro and in vivo. The complex disrupted the ulcerative process as demonstrated by changes in the intermediate metabolites of the oxidative pathway – specifically, reduction in the MDA levels and elevation of reduced glutathione together with an attenuation of oxidative DNA damage. Additionally, Zn(L)SCN restored the gastric mucosa, inhibited the production of pro-inflammatory cytokines (IL-6, TNF and the caspases), and preserved the gastric mucous balance. Zn(L)SCN thus exhibited anti-oxidative, anti-inflammatory and anti-apoptotic activities, all of which have cytoprotective effects on the gastric lining.
Multiscale Cues Drive Collective Cell Migration
Authors: Nam Ki-Hwan , Kim Peter , Wood David K. , Kwon Sunghoon , Provenzano Paolo P. , Kim Deok-Ho 
Published: July 2016

AbstractTo investigate complex biophysical relationships driving directed cell migration, we developed a biomimetic platform that allows perturbation of microscale geometric constraints with concomitant nanoscale contact guidance architectures. This permits us to elucidate the influence, and parse out the relative contribution, of multiscale features, and define how these physical inputs are jointly processed with oncogenic signaling. We demonstrate that collective cell migration is profoundly enhanced by the addition of contract guidance cues when not otherwise constrained. However, while nanoscale cues promoted migration in all cases, microscale directed migration cues are dominant as the geometric constraint narrows, a behavior that is well explained by stochastic diffusion anisotropy modeling. Further, oncogene activation (i.e. mutant PIK3CA) resulted in profoundly increased migration where extracellular multiscale directed migration cues and intrinsic signaling synergistically conspire to greatly outperform normal cells or any extracellular guidance cues in isolation.
Gastrointestinal Spatiotemporal mRNA Expression of Ghrelin vs Growth Hormone Receptor and New Growth Yield Machine Learning Model Based on Perturbation Theory
Authors: Ran Tao , Liu Yong , Li Hengzhi , Tang Shaoxun , He Zhixiong , Munteanu Cristian R. , González-Díaz Humberto , Tan Zhiliang , Zhou Chuanshe 
Published: July 2016

AbstractThe management of ruminant growth yield has economic importance. The current work presents a study of the spatiotemporal dynamic expression ofGhrelinandGHRat mRNA levels throughout the gastrointestinal tract (GIT) of kid goats under housing and grazing systems. The experiments show that the feeding system and age affected the expression of either Ghrelin or GHR with different mechanisms. Furthermore, the experimental data are used to build new Machine Learning models based on the Perturbation Theory, which can predict the effects of perturbations ofGhrelinandGHRmRNA expression on the growth yield. The models consider eight longitudinal GIT segments (rumen, abomasum, duodenum, jejunum, ileum, cecum, colon and rectum), seven time points (0, 7, 14, 28, 42, 56 and 70 d) and two feeding systems (Supplemental and Grazing feeding) as perturbations from the expected values of the growth yield. The best regression model was obtained using Random Forest, with the coefficient of determination R2of 0.781 for the test subset. The current results indicate that the non-linear regression model can accurately predict the growth yield and the key nodes during gastrointestinal development, which is helpful to optimize the feeding management strategies in ruminant production system.
BATCH-GE: Batch analysis of Next-Generation Sequencing data for genome editing assessment
Authors: Boel Annekatrien , Steyaert Woutert , De Rocker Nina , Menten Björn , Callewaert Bert , De Paepe Anne , Coucke Paul , Willaert Andy 
Published: July 2016

AbstractTargeted mutagenesis by the CRISPR/Cas9 system is currently revolutionizing genetics. The ease of this technique has enabled genome engineering in-vitro and in a range of model organisms and has pushed experimental dimensions to unprecedented proportions. Due to its tremendous progress in terms of speed, read length, throughput and cost, Next-Generation Sequencing (NGS) has been increasingly used for the analysis of CRISPR/Cas9 genome editing experiments. However, the current tools for genome editing assessment lack flexibility and fall short in the analysis of large amounts of NGS data. Therefore, we designed BATCH-GE, an easy-to-use bioinformatics tool for batch analysis of NGS-generated genome editing data, available from http://. BATCH-GE detects and reports indel mutations and other precise genome editing events and calculates the corresponding mutagenesis efficiencies for a large number of samples in parallel. Furthermore, this new tool provides flexibility by allowing the user to adapt a number of input variables. The performance of BATCH-GE was evaluated in two genome editing experiments, aiming to generate knock-out and knock-in zebrafish mutants. This tool will not only contribute to the evaluation of CRISPR/Cas9-based experiments, but will be of use in any genome editing experiment and has the ability to analyze data from every organism with a sequenced genome.
The regulation of thermal stress induced apoptosis in corals reveals high similarities in gene expression and function to higher animals
Authors: Kvitt Hagit , Rosenfeld Hanna , Tchernov Dan 
Published: July 2016

AbstractRecent studies suggest that controlled apoptotic response provides an essential mechanism, enabling corals to respond to global warming and ocean acidification. However, the molecules involved and their functions are still unclear. To better characterize the apoptotic response in basal metazoans, we studied the expression profiles of selected genes that encode for putative pro- and anti-apoptotic mediators in the coral Stylophora pistillata under thermal stress and bleaching conditions. Upon thermal stress, as attested by the elevation of the heat-shock protein gene HSP70’s mRNA levels, the expression of all studied genes, including caspase, Bcl-2, Bax, APAF-1 and BI-1, peaked at 6–24 h of thermal stress (hts) and declined at 72 hts. Adversely, the expression levels of the survivin gene showed a shifted pattern, with elevation at 48–72 hts and a return to basal levels at 168 hts. Overall, we show the quantitative anti-apoptotic traits of the coral Bcl-2 protein, which resemble those of its mammalian counterpart. Altogether, our results highlight the similarities between apoptotic networks operating in simple metazoans and in higher animals and clearly demonstrate the activation of pro-cell survival regulators at early stages of the apoptotic response, contributing to the decline of apoptosis and the acclimation to chronic stress.
Haplotyping the human leukocyte antigen system from single chromosomes
Authors: Murphy Nicholas M. , Burton Matthew , Powell David R. , Rossello Fernando J. , Cooper Don , Chopra Abha , Hsieh Ming Je , Sayer David C. , Gordon Lavinia , Pertile Mark D , Tait Brian D. , Irving Helen R. , Pouton Colin W. 
Published: July 2016

AbstractWe describe a method for determining the parental HLA haplotypes of a single individual without recourse to conventional segregation genetics. Blood samples were cultured to identify and sort chromosome 6 by bivariate flow cytometry. Single chromosome 6 amplification products were confirmed with a single nucleotide polymorphism (SNP) array and verified by deep sequencing to enable assignment of both alleles at the HLA loci, defining the two haplotypes. This study exemplifies a rapid and efficient method of haplotyping that can be applied to any chromosome pair, or indeed all chromosome pairs, using a single sorting operation. The method represents a cost-effective approach to complete phasing of SNPs, which will facilitate a deeper understanding of the links between SNPs, gene regulation and protein function.
Dose-Dependent Suppression of Cytokine production from T cells by a Novel Phosphoinositide 3-Kinase Delta Inhibitor
Authors: Way Emily E. , Trevejo-Nunez Giraldina , Kane Lawrence P. , Steiner Bart H. , Puri Kamal D. , Kolls Jay K. , Chen Kong 
Published: July 2016

AbstractThere remains a significant need for development of effective small molecules that can inhibit cytokine-mediated inflammation. Phosphoinositide 3 kinase (PI3K) is a direct upstream activator of AKT, and plays a critical role in multiple cell signaling pathways, cell cycle progression, and cell growth, and PI3K inhibitors have been approved or are in clinical development. We examined novel PI3Kdelta inhibitors, which are highly selective for the p110delta isoform of in CD3/CD28 stimulated T-cell cytokine production. In vitro generated CD4+ T effector cells stimulated in the presence of a PI3Kdelta inhibitor demonstrated a dose-dependent suppression of cytokines produced by Th1, Th2, and Th17 cells. This effect was T-cell intrinsic, and we observed similar effects on human PBMCs. Th17 cells expressing a constitutively activated form of AKT were resistant to PI3Kdelta inhibition, suggesting that the inhibitor is acting through AKT signaling pathways. Additionally, PI3Kdelta inhibition decreased IL-17 production in vivo and decreased neutrophil recruitment to the lung in a murine model of acute pulmonary inflammation. These experiments show that targeting PI3Kdelta activity can modulate T-cell cytokine production and reduce inflammation in vivo, suggesting that PI3Kdelta inhibition could have therapeutic potential in treating inflammatory diseases.
Spontaneous formation of spiral-like patterns with distinct periodic physical properties by confined electrodeposition of Co-In disks
Authors: Golvano-Escobal Irati , Gonzalez-Rosillo Juan Carlos , Domingo Neus , Illa Xavi , López-Barberá José Francisco , Fornell Jordina , Solsona Pau , Aballe Lucia , Foerster Michael , Suriñach Santiago , Baró Maria Dolors , Puig Teresa , Pané Salvador , Nogués Josep , Pellicer Eva , Sort Jordi 
Published: July 2016

AbstractSpatio-temporal patterns are ubiquitous in different areas of materials science and biological systems. However, typically the motifs in these types of systems present a random distribution with many possible different structures. Herein, we demonstrate that controlled spatio-temporal patterns, with reproducible spiral-like shapes, can be obtained by electrodeposition of Co-In alloys inside a confined circular geometry (i.e., in disks that are commensurate with the typical size of the spatio-temporal features). These patterns are mainly of compositional nature, i.e., with virtually no topographic features. Interestingly, the local changes in composition lead to a periodic modulation of the physical (electric, magnetic and mechanical) properties. Namely, the Co-rich areas show higher saturation magnetization and electrical conductivity and are mechanically harder than the In-rich ones. Thus, this work reveals that confined electrodeposition of this binary system constitutes an effective procedure to attain template-free magnetic, electric and mechanical surface patterning with specific and reproducible shapes.
Liposomal prednisolone inhibits vascular inflammation and enhances venous outward remodeling in a murine arteriovenous fistula model
Authors: Wong ChunYu , Bezhaeva Taisiya , Rothuizen Tonia C. , Metselaar Josbert M. , de Vries Margreet R. , Verbeek Floris P. R. , Vahrmeijer Alexander L. , Wezel Anouk , van Zonneveld Anton-Jan , Rabelink Ton J. , Quax Paul H. A. , Rotmans Joris I. 
Published: July 2016

AbstractArteriovenous fistulas (AVF) for hemodialysis access have a 1-year primary patency rate of only 60%, mainly as a result of maturation failure that is caused by insufficient outward remodeling and intimal hyperplasia. The exact pathophysiology remains unknown, but the inflammatory vascular response is thought to play an important role. In the present study we demonstrate that targeted liposomal delivery of prednisolone increases outward remodeling of the AVF in a murine model. Liposomes accumulate in the post-anastomotic area of the venous outflow tract in which the vascular pathology is most prominent in failed AVFs. On a histological level, we observed a reduction of lymphocytes and granulocytes in the vascular wall. In addition, a strong anti-inflammatory effect of liposomal prednisolone on macrophages was demonstrated in vitro. Therefore, treatment with liposomal prednisolone might be a valuable strategy to improve AVF maturation.
Intensified Springtime Deep Convection over the South China Sea and the Philippine Sea Dries Southern China
Authors: Li Zhenning , Yang Song , He Bian , Hu Chundi 
Published: July 2016

AbstractSpringtime rainfall, accounting for 25–40% of the annual rainfall in southern China, exerts great agricultural and socioeconomic impacts on the region. In the recent decades, southern China has experienced a significant declining trend of precipitation in boreal spring. Meanwhile, precipitation has increased over the South China Sea and the Philippine Sea (SCS-PhS). This paper presents observational and modeling evidences suggesting that the intensified latent heating released by the convection over SCS-PhS leads to suppressed springtime rainfall over southern China. Moisture budget analysis indicates that the drying trend over southern China is due mainly to weakened convergence of moisture flux, which is controlled by a heat-induced anomalous overturning circulation reinforced by the convection over SCS-PhS. Further idealized simulations support the feature that the heat-induced overturning circulation and its corresponding anomalous cyclone can be well established in several days under the spring mean flow condition. Thus, this rapid dynamic process is associated with both the intraseasonal-to-interannual variations and the long-term change of the springtime rainfall over southern China.
Identification of a novel inactivating mutation in Isocitrate Dehydrogenase 1 (IDH1-R314C) in a high grade astrocytoma
Authors: van Lith Sanne A. M. , Navis Anna C. , Lenting Krissie , Verrijp Kiek , Schepens Jan T. G. , Hendriks Wiljan J. A. J. , Schubert Nil A. , Venselaar Hanka , Wevers Ron A. , van Rooij Arno , Wesseling Pieter , Molenaar Remco J. , van Noorden Cornelis J. F. , Pusch Stefan , Tops Bastiaan , Leenders William P. J. 
Published: July 2016

AbstractThe majority of low-grade and secondary high-grade gliomas carry heterozygous hotspot mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) or the mitochondrial variant IDH2. These mutations mostly involve Arg132 in IDH1 and Arg172 or Arg140 in IDH2. Whereas IDHs convert isocitrate to alpha-ketoglutarate (α-KG) with simultaneous reduction of NADP+ to NADPH, these IDH mutants reduce α-KG to D-2-hydroxyglutarate (D-2-HG) while oxidizing NADPH. D-2-HG is a proposed oncometabolite, acting via competitive inhibition of α-KG-dependent enzymes that are involved in metabolism and epigenetic regulation. However, much less is known about the implications of the metabolic stress, imposed by decreased α-KG and NADPH production, for tumor biology. We here present a novel heterozygous IDH1 mutation, IDH1R314C, which was identified by targeted next generation sequencing of a high grade glioma from which a mouse xenograft model and a cell line were generated. IDH1R314C lacks isocitrate-to-α-KG conversion activity due to reduced affinity for NADP+ and differs from the IDH1R132 mutants in that it does not produce D-2-HG. Because IDH1R314C is defective in producing α-KG and NADPH, without concomitant production of the D-2-HG, it represents a valuable tool to study the effects of IDH1-dysfunction on cellular metabolism in the absence of this oncometabolite.
Sitagliptin and risk of heart failure hospitalization in patients with type 2 diabetes on dialysis: A population-based cohort study
Authors: Hung Yi-Chih , Lin Che-Chen , Huang Wei-Lun , Chang Man-Ping , Chen Ching-Chu 
Published: July 2016

AbstractThe incidence of heart failure hospitalization (HHF) after taking sitagliptin in type 2 diabetes (T2DM) patients with end stage renal disease (ESRD) on dialysis is unclear. In this population-based cohort study, we identified individuals with T2DM and ESRD on dialysis who were treated with sitagliptin between 2009 and 2011 and randomly selected a control cohort matched by age, sex, duration of T2DM, hypertension medications, use of statin and aspirin, sulfonylureas, glinides, and insulin usage, atherosclerotic heart disease, congestive heart failure and chronic obstructive pulmonary disease at a 1:4 ratio. Multivariable Cox proportional hazards regression analysis was used to evaluate HHF risk. The overall incidence of HHF was higher in the sitagliptin cohort than in the control cohort (1130 vs. 754 per 10000 person-years; adjusted hazard ratio (HR): 1.52, 95% CI = 1.21–1.90). There was a significant trend towards increased HHF risk associated with increased sitagliptin dose (p for trend < 0.01). Subjects at greater risk of HHF after taking sitagliptin were those without severe hypoglycemia, without ACE inhibitors treatment, with history of heart failure or receiving hemodialysis rather than peritoneal dialysis. In conclusion, use of sitagliptin was associated with an increased risk of HHF in patients with T2DM on dialysis.
Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells
Authors: Montagnani Marelli Marina , Marzagalli Monica , Moretti Roberta M. , Beretta Giangiacomo , Casati Lavinia , Comitato Raffaella , Gravina Giovanni L. , Festuccia Claudio , Limonta Patrizia 
Published: July 2016

AbstractMalignant melanoma is the leading cause of death from skin cancer. Drug toxicity and resistance represent a serious challange for melanoma treatments. Evidence demonstrates that natural compounds may play a crucial role in cancer prevention, growth and progression. Vitamin E tocotrienols (TT) were shown to possess antitumor activity. Here, we analyzed the effects of δ-TT on melanoma cell growth and the involvement of the endoplasmic reticulum (ER) stress in this activity. The experiments were performed on human melanoma cell lines, BLM and A375. δ-TT exerted a significant proapoptotic effect on both cell lines, involving the intrinsic apoptosis pathway; importantly, this compound did not affect the viability of normal human melanocytes. In melanoma cells, δ-TT exerted its antitumor effect through activation of the PERK/p-eIF2α/ATF4/CHOP, IRE1α and caspase-4 ER stress-related branches. Salubrinal, an inhibitor of the ER stress, counteracted the cytotoxic activity of δ-TT. In vivo experiments performed in nude mice bearing A375 xenografts evidenced that δ-TT reduces tumor volume and tumor mass; importantly, tumor progression was significantly delayed by δ-TT treatment. In conclusion, δ-TT exerts a proapoptotic activity on melanoma cells, through activation of the ER stress-related pathways. δ-TT might represent an effective option for novel chemopreventive/therapeutic strategies for melanoma.
Platelet activation risk index as a prognostic thrombosis indicator
Authors: Zlobina K. E. , Guria G. Th. 
Published: July 2016

AbstractPlatelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor. Despite the large amount of experimental data that have been obtained, the value of the critical shear rate, above which von Willebrand factor starts to activate platelets, is still controversial. Here, we recommend a theoretical approach to elucidate how the critical blood shear rate is dependent on von Willebrand factor size. We derived a diagram of platelet activation according to the shear rate and von Willebrand factor multimer size. We succeeded in deriving an explicit formula for the dependence of the critical shear rate on von Willebrand factor molecule size. The platelet activation risk index was introduced. This index is dependent on the flow conditions, number of monomers in von Willebrand factor and platelet sensitivity. Probable medical applications of the platelet activation risk index as a universal prognostic index are discussed.
Enrichment of risk SNPs in regulatory regions implicate diverse tissues in Parkinson’s disease etiology
Authors: Coetzee Simon G. , Pierce Steven , Brundin Patrik , Brundin Lena , Hazelett Dennis J. , Coetzee Gerhard A. 
Published: July 2016

AbstractRecent genome-wide association studies (GWAS) of Parkinson’s disease (PD) revealed at least 26 risk loci, with associated single nucleotide polymorphisms (SNPs) located in non-coding DNA having unknown functions in risk. In order to explore in which cell types these SNPs (and their correlated surrogates at r2 ≥ 0.8) could alter cellular function, we assessed their location overlap with histone modification regions that indicate transcription regulation in 77 diverse cell types. We found statistically significant enrichment of risk SNPs at 12 loci in active enhancers or promoters. We investigated 4 risk loci in depth that were most significantly enriched (−logeP > 14) and contained 8 putative enhancers in the different cell types. These enriched loci, along with eQTL associations, were unexpectedly present in non-neuronal cell types. These included lymphocytes, mesendoderm, liver- and fat-cells, indicating that cell types outside the brain are involved in the genetic predisposition to PD. Annotating regulatory risk regions within specific cell types may unravel new putative risk mechanisms and molecular pathways that contribute to PD development.
Concatenation of ‘alert’ and ‘identity’ segments in dingoes’ alarm calls
Authors: Déaux Eloïse C. , Allen Andrew P. , Clarke Jennifer A. , Charrier Isabelle 
Published: July 2016

AbstractMulticomponent signals can be formed by the uninterrupted concatenation of multiple call types. One such signal is found in dingoes, Canis familiaris dingo. This stereotyped, multicomponent ‘bark-howl’ vocalisation is formed by the concatenation of a noisy bark segment and a tonal howl segment. Both segments are structurally similar to bark and howl vocalisations produced independently in other contexts (e.g. intra- and inter-pack communication). Bark-howls are mainly uttered in response to human presence and were hypothesized to serve as alarm calls. We investigated the function of bark-howls and the respective roles of the bark and howl segments. We found that dingoes could discriminate between familiar and unfamiliar howl segments, after having only heard familiar howl vocalisations (i.e. different calls). We propose that howl segments could function as ‘identity signals’ and allow receivers to modulate their responses according to the caller’s characteristics. The bark segment increased receivers’ attention levels, providing support for earlier observational claims that barks have an ‘alerting’ function. Lastly, dingoes were more likely to display vigilance behaviours upon hearing bark-howl vocalisations, lending support to the alarm function hypothesis. Canid vocalisations, such as the dingo bark-howl, may provide a model system to investigate the selective pressures shaping complex communication systems.