bluuebunny/crossref_metadata_2025 huggingface dataset:
Pentlandite rocks as sustainable and stable efficient electrocatalysts for hydrogen generation
Authors: Konkena Bharathi , junge Puring Kai , Sinev Ilya , Piontek Stefan , Khavryuchenko Oleksiy , Dürholt Johannes P. , Schmid Rochus , Tüysüz Harun , Muhler Martin , Schuhmann Wolfgang , Apfel Ulf-Peter
Published: July 2016

The need for sustainable catalysts for an efficient hydrogen evolution reaction is of significant interest for modern society. Inspired by comparable structural properties of [FeNi]-hydrogenase, here we present the natural ore pentlandite (Fe4.5Ni4.5S8) as a direct ‘rock’ electrode material for hydrogen evolution under acidic conditions with an overpotential of 280 mV at 10 mA cm−2. Furthermore, it reaches a value as low as 190 mV after 96 h of electrolysis due to surface sulfur depletion, which may change the electronic structure of the catalytically active nickel–iron centres. The ‘rock’ material shows an unexpected catalytic activity with comparable overpotential and Tafel slope to some well-developed metallic or nanostructured catalysts. Notably, the ‘rock’ material offers high current densities (≤650 mA cm−2) without any loss in activity for approximately 170 h. The superior hydrogen evolution performance of pentlandites as ‘rock’ electrode labels this ore as a promising electrocatalyst for future hydrogen-based economy.
CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity
Authors: Jacoby Elad , Nguyen Sang M. , Fountaine Thomas J. , Welp Kathryn , Gryder Berkley , Qin Haiying , Yang Yinmeng , Chien Christopher D. , Seif Alix E. , Lei Haiyan , Song Young K. , Khan Javed , Lee Daniel W. , Mackall Crystal L. , Gardner Rebecca A. , Jensen Michael C. , Shern Jack F. , Fry Terry J.
Published: July 2016

Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy. Using murine ALL models we study the long-term effects of CD19 CAR-T cells and demonstrate partial or complete lineage switch as a consistent mechanism of CAR resistance depending on the underlying genetic oncogenic driver. Deletion of Pax5 or Ebf1 recapitulates lineage reprogramming occurring during CD19 CAR pressure. Our findings establish lineage switch as a mechanism of CAR resistance exposing inherent plasticity in genetic subtypes of pre-B-cell ALL.
Structural and compositional dependence of the CdTexSe1−x alloy layer photoactivity in CdTe-based solar cells
Authors: Poplawsky Jonathan D. , Guo Wei , Paudel Naba , Ng Amy , More Karren , Leonard Donovan , Yan Yanfa
Published: July 2016

The published external quantum efficiency data of the world-record CdTe solar cell suggests that the device uses bandgap engineering, most likely with a CdTexSe1−x alloy layer to increase the short-circuit current and overall device efficiency. Here atom probe tomography, transmission electron microscopy and electron beam-induced current are used to clarify the dependence of Se content on the photoactive properties of CdTexSe1−x alloy layers in bandgap-graded CdTe solar cells. Four solar cells were prepared with 50, 100, 200 and 400 nm-thick CdSe layers to reveal the formation, growth, composition, structure and photoactivity of the CdTexSe1−x alloy with respect to the degree of Se diffusion. The results show that the CdTexSe1−x layer photoactivity is highly dependent on the crystalline structure of the alloy (zincblende versus wurtzite), which is also dependent on the Se and Te concentrations.
Arabinoxylans, inulin and Lactobacillus reuteri 1063 repress the adherent-invasive Escherichia coli from mucus in a mucosa-comprising gut model
Authors: Van den Abbeele Pieter , Marzorati Massimo , Derde Melanie , De Weirdt Rosemarie , Joan Vermeiren , Possemiers Sam , Van de Wiele Tom
Published: July 2016

The microbiota that colonises the intestinal mucus may particularly affect human health given its proximity to the epithelium. For instance, the presence of the adherent-invasive Escherichia coli (AIEC) in this mucosal microbiota has been correlated with Crohn’s disease. Using short-term screening assays and a novel long-term dynamic gut model, which comprises a simulated mucosal environment (M-SHIME), we investigated how (potential) pro- and prebiotics may repress colonisation of AIEC from mucus. Despite that during the short-term screening assays, some of the investigated Lactobacillus strains adhered strongly to mucins, none of them competed with AIEC for mucin-adhesion. In contrast, AIEC survival and growth during co-culture batch incubations was decreased by Lactobacillus rhamnosus GG and L. reuteri 1063, which correlated with (undissociated) lactic acid and reuterin levels. Regarding the prebiotics, long-chain arabinoxylans (LC-AX) lowered the initial mucin-adhesion of AIEC, while both inulin (IN) and galacto-oligosaccharides (GOS) limited AIEC survival and growth during batch incubations. L. reuteri 1063, LC-AX and IN were thus retained for a long-term study with the M-SHIME. All treatments repressed AIEC from mucus without affecting AIEC numbers in the luminal content. As a possible explanation, L. reuteri 1063 treatment increased lactobacilli levels in mucus, while LC-AX and IN additionally increased mucosal bifidobacteria levels, thus leading to antimicrobial effects against AIEC in mucus. Overall, this study shows that pro- and prebiotics can beneficially modulate the in vitro mucosal microbiota, thus limiting occurrence of opportunistic pathogens among those mucosal microbes which may directly interact with the host given their proximity to the epithelium.
Composition dependence of charge and magnetic length scales in mixed valence manganite thin films
Authors: Singh Surendra , Freeland J. W. , Fitzsimmons M. R. , Jeen H. , Biswas A.
Published: July 2016

Mixed-valence manganese oxides present striking properties like the colossal magnetoresistance, metal-insulator transition (MIT) that may result from coexistence of ferromagnetic, metallic and insulating phases. Percolation of such phase coexistence in the vicinity of MIT leads to first-order transition in these manganites. However the length scales over which the electronic and magnetic phases are separated across MIT which appears compelling for bulk systems has been elusive in (La1−yPry)1−xCaxMnO3 films. Here we show the in-plane length scale over which charge and magnetism are correlated in (La0.4Pr0.6)1−xCaxMnO3 films with x = 0.33 and 0.375, across the MIT temperature. We combine electrical transport (resistance) measurements, x-ray absorption spectroscopy (XAS), x-ray magnetic circular dichroism (XMCD), and specular/off-specular x-ray resonant magnetic scattering (XRMS) measurements as a function of temperature to elucidate relationships between electronic, magnetic and morphological structure of the thin films. Using off-specular XRMS we obtained the charge-charge and charge-magnetic correlation length of these LPCMO films across the MIT. We observed different charge-magnetic correlation length for two films which increases below the MIT. The different correlation length shown by two films may be responsible for different macroscopic (transport and magnetic) properties.
A cholesterol-binding domain in STIM1 modulates STIM1-Orai1 physical and functional interactions
Authors: Pacheco Jonathan , Dominguez Laura , Bohórquez-Hernández A. , Asanov Alexander , Vaca Luis
Published: July 2016

STIM1 and Orai1 are the main components of a widely conserved Calcium influx pathway known as store-operated calcium entry (SOCE). STIM1 is a calcium sensor, which oligomerizes and activates Orai channels when calcium levels drop inside the endoplasmic reticulum (ER). The series of molecular rearrangements that STIM1 undergoes until final activation of Orai1 require the direct exposure of the STIM1 domain known as SOAR (Stim Orai Activating Region). In addition to these complex molecular rearrangements, other constituents like lipids at the plasma membrane, play critical roles orchestrating SOCE. PI(4,5)P2 and enriched cholesterol microdomains have been shown as important signaling platforms that recruit the SOCE machinery in steps previous to Orai1 activation. However, little is known about the molecular role of cholesterol once SOCE is activated. In this study we provide clear evidence that STIM1 has a cholesterol-binding domain located inside the SOAR region and modulates Orai1 channels. We demonstrate a functional association of STIM1 and SOAR to cholesterol, indicating a close proximity of SOAR to the inner layer of the plasma membrane. In contrast, the depletion of cholesterol induces the SOAR detachment from the plasma membrane and enhances its association to Orai1. These results are recapitulated with full length STIM1.
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

Zinc 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

To 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

The 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

Targeted 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

Recent 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

We 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

There 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

Spatio-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

Arteriovenous 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

Springtime 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

The 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

The 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

Malignant 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

Platelet 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

Recent 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

Multicomponent 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.
Efficient double-quenching of electrochemiluminescence from CdS:Eu QDs by hemin-graphene-Au nanorods ternary composite for ultrasensitive immunoassay
Authors: Liu Jing , Cui Meirong , Zhou Hong , Zhang Shusheng
Published: July 2016

A novel ternary composite of hemin-graphene-Au nanorods (H-RGO-Au NRs) with high electrocatalytic activity was synthesized by a simple method. And this ternary composite was firstly used in construction of electrochemiluminescence (ECL) immunosensor due to its double-quenching effect of quantum dots (QDs). Based on the high electrocatalytic activity of ternary complexes for the reduction of H2O2 which acted as the coreactant of QDs-based ECL, as a result, the ECL intensity of QDs decreased. Besides, due to the ECL resonance energy transfer (ECL-RET) strategy between the large amount of Au nanorods (Au NRs) on the ternary composite surface and the CdS:Eu QDs, the ECL intensity of QDs was further quenched. Based on the double-quenching effect, a novel ultrasensitive ECL immunoassay method for detection of carcinoembryonic antigen (CEA) which is used as a model biomarker analyte was proposed. The designed immunoassay method showed a linear range from 0.01 pg mL−1 to 1.0 ng mL−1 with a detection limit of 0.01 pg mL−1. The method showing low detection limit, good stability and acceptable fabrication reproducibility, provided a new approach for ECL immunoassay sensing and significant prospect for practical application.
Magnetic Resonance Imaging of Glucose Uptake and Metabolism in Patients with Head and Neck Cancer
Authors: Wang Jihong , Weygand Joseph , Hwang Ken-Pin , Mohamed Abdallah S. R. , Ding Yao , Fuller Clifton D. , Lai Stephen Y. , Frank Steven J. , Zhou Jinyuan
Published: July 2016

Imaging metabolic dysfunction, a hallmark of solid tumors, usually requires radioactive tracers. Chemical exchange saturation transfer (CEST) imaging can potentially detect and visualize glucose uptake and metabolism, without the need for radioisotopes. Here, we tested the feasibility of using glucose CEST (glucoCEST) to image unlabeled glucose uptake in head and neck cancer by using a clinical 3T magnetic resonance imaging (MRI) scanner. The average CEST contrast between tumors and normal tissue in 17 patients was 7.58% (P = 0.006) in the 3–4 ppm offset frequency range and 5.06% (P = 0.02) in 1–5 ppm range. In a subgroup of eight patients, glucoCEST signal enhancement was higher in tumors than in normal muscle (4.98% vs. 1.28%, P < 0.021). We conclude that glucoCEST images of head and neck cancer can be obtained with a clinical 3T MRI scanner.
Exploring the effect of laser excitation wavelength on signal recovery with deep tissue transmission Raman spectroscopy
Authors: Ghita Adrian , Matousek Pavel , Stone Nicholas
Published: July 2016

The aim of this research was to find the optimal Raman excitation wavelength to attain the largest possible sensitivity in deep Raman spectroscopy of breast tissue.
Epigenetic changes in cancer by Raman imaging, fluorescence imaging, AFM and scanning near-field optical microscopy (SNOM). Acetylation in normal and human cancer breast cells MCF10A, MCF7 and MDA-MB-231
Authors: Abramczyk Halina , Surmacki Jakub , Kopeć Monika , Olejnik Alicja Klaudia , Kaufman-Szymczyk Agnieszka , Fabianowska-Majewska Krystyna
Published: July 2016

This paper examines epigenetic changes in breast cancer cells by Raman imaging, fluorescence imaging, AFM and SNOM.
3D-printed microfluidic devices: fabrication, advantages and limitations—a mini review
Authors: Chen Chengpeng , Mehl Benjamin T. , Munshi Akash S. , Townsend Alexandra D. , Spence Dana M. , Martin R. Scott
Published: July 2016

A mini-review that focuses on the most recent trends in 3D-printed microfluidic devices, with sample designs that can be downloaded for use.
Reversibly tuning the mechanical properties of a DNA hydrogel by a DNA nanomotor
Authors: Zhou Xu , Li Chuang , Shao Yu , Chen Chun , Yang Zhongqiang , Liu Dongsheng
Published: July 2016

The microscopic conformational transition of an i-motif sequence integrated into a DNA hydrogel network leads to a reversible change in the macroscopic mechanical properties of the hydrogel without changing its initial topological structure.
Encapsulation capacity and natural payload delivery of an anticancer drug from boron nitride nanotube
Authors: El Khalifi M. , Bentin J. , Duverger E. , Gharbi T. , Boulahdour H. , Picaud F.
Published: July 2016

Payload delivery of anticancer cisplatin molecules assisted by the cell membrane lipid.
Spectroscopic study on the active site of a SiO2 supported niobia catalyst used for the gas-phase Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam
Authors: Maronna M. M. , Kruissink E. C. , Parton R. F. , Soulimani F. , Weckhuysen B. M. , Hoelderich W. F.
Published: July 2016

Formation of a Brønsted-acidic site out of a Lewis-acidic mono-oxo NbO4 surface species and ethanol, catalysed by a Lewis-basic molecule, e.g. pyridine or cyclohexanone oxime.
Small molecule based N-phenyl carbazole substituted diketopyrrolopyrroles as donors for solution-processed bulk heterojunction organic solar cells
Authors: Patil Yuvraj , Misra Rajneesh , Chen F. C. , Sharma Ganesh D.
Published: July 2016

We report two acetylene-bridged small molecules DPP5 and DPP6 with low HOMO–LUMO gaps as donors along with PC71BM as an acceptor for the fabrication of solution-processed bulk heterojunction solar cells.
Chemical tools for interrogating inositol pyrophosphate structure and function
Authors: Brown Nathaniel W. , Marmelstein Alan M. , Fiedler Dorothea
Published: July 2016

New chemical and analytical tools have been developed to study the diverse functions of the inositol pyrophosphates, a unique group of densely phosphorylated intracellular metabolites found in a wide variety of eukaryotic organisms.
Hematite heterostructures for photoelectrochemical water splitting: rational materials design and charge carrier dynamics
Authors: Shen Shaohua , Lindley Sarah A. , Chen Xiangyan , Zhang Jin Z.
Published: July 2016

Different approaches to improving photoelectrochemical performance through α-Fe2O3 heterostructure design.
Synthesis of phenols from hydroxymethylfurfural (HMF)
Authors: Tšupova Svetlana , Rominger Frank , Rudolph Matthias , Hashmi A. Stephen K.
Published: July 2016

HMF-derived substrates were converted to highly substituted phenols by gold catalysis.
Design and synthesis of DNA-encoded libraries based on a benzodiazepine and a pyrazolopyrimidine scaffold
Authors: Škopić M. Klika , Bugain O. , Jung K. , Onstein S. , Brandherm S. , Kalliokoski T. , Brunschweiger A.
Published: July 2016

DNA-encoded libraries based on scaffolds functionalized for DNA-compatible chemistry were synthesized by split-and-pool combinatorial chemistry. The library design was aided by a chemoinformatic filtering cascade.
Potentiation of the fosmidomycin analogue FR 900098 with substituted 2-oxazolines against Francisella novicida
Authors: Stephens Matthew D. , Yodsanit Nisakorn , Melander Christian
Published: July 2016

A library of 33 compounds was screened for potentiation of the antibiotic FR 900098 against the Francisella tularensis surrogate Francisella novicida.
Buckypaper templating Ni–Co hydroxide nanosheets as free-standing electrodes for ultrathin and flexible supercapacitors
Authors: Wang Xinxue , Song Tianshu
Published: July 2016

A novel sheet-on-tube hierarchical structure with a uniform distribution of Ni–Co hydroxides on BP acts as a promising supercapacitor.
Copper-catalyzed synthesis of benzoxazoles via tandem cyclization of 2-halophenols with amidines
Authors: Tiwari Abhishek R. , Bhanage Bhalchandra M.
Published: July 2016

This work reports a simple, efficient and alternative synthetic route for the preparation of benzoxazolesviatandem cyclization of 2-halophenols with amidines.
Synthesis and reactivity of alkoxy-activated cyclobutane-1,1-dicarboxylates
Authors: Vemula Naresh , Pagenkopf Brian L.
Published: July 2016

Donor–acceptor (DA) cyclopropanes are extensively studied and well established as building blocks for the synthesis of highly substituted carbo- and heterocyclic compounds. Despite of similar ring strain, the homologous DA cyclobutanes were long ignored. This personal account details our group's research towards the application of DA cyclobutanes in cycloaddition chemistry.
Synthesis, characterization and application of Ni0.5Zn0.5Fe2O4 nanoparticles for the one pot synthesis of triaryl-1H-imidazoles
Authors: Khazaei Ardeshir , Alavi Nik Heidar Ali , Ranjbaran Azam , Moosavi-Zare Ahmad Reza
Published: July 2016

Ni0.5Zn0.5Fe2O4 nanopowder, as a highly efficient and heterogeneous catalyst, was employed for the synthesis of 2,4,5-triaryl substituted imidazoles.
Role of para-substitution in controlling phosphatase activity of dinuclear NiII complexes of Mannich-base ligands: experimental and DFT studies
Authors: Sanyal Ria , Zhang Xuepeng , Chakraborty Prateeti , Mautner Franz A. , Zhao Cunyuan , Das Debasis
Published: July 2016

Five dinuclear NiII complexes synthesized by Mannich reaction portray remarkable phosphatase activity where the tert-butyl complex exhibits the maximum reactivity.
Tuning the phase transition temperature, electrical and optical properties of VO2 by oxygen nonstoichiometry: insights from first-principles calculations
Authors: Chen Lanli , Wang Xiaofang , Wan Dongyun , Cui Yuanyuan , Liu Bin , Shi Siqi , Luo Hongjie , Gao Yanfeng
Published: July 2016

The O-vacancy in bulk VO2 gives rise to an increase in electron concentration, which induces a decrease in Tc. While, O-vacancy and O-adsorption on VO2(R) (1 1 0) and VO2(M) (0 1 1) surfaces could alter the work functions and in turn regulate Tc.
Porous structured MIL-101 synthesized with different mineralizers for adsorptive removal of oxytetracycline from aqueous solution
Authors: Hu Tianding , Lv Hongting , Shan Shaoyun , Jia Qingming , Su Hongying , Tian Na , He Shanchuan
Published: July 2016

In this work, highly porous MIL-101 materials using hydrochloric acid (HCl) or hydrofluoric acid (HF) as a mineralizer were synthesized.
Neuroprotective effects of nitidine in Parkinson's disease models through inhibiting microglia activation: role of the Jak2–Stat3 pathway
Authors: Wang Bao , Wang Xing-qin , Yang Shao-song , Liu Xi , Feng Da-yun , Lu Fang-fang , Zhu Ya-qin , Lu Dan , Tao Lei , Ge Shun-nan , Gao Li , Qu Yan , Gao Guo-dong
Published: July 2016

In this work we found that nitidine could significantly suppress microglial activationviathe Jak2–Stat3 pathway and obviously improve behavioural function in Parkinson's disease (PD) animal models, which sheds light on PD treatment.
Decarboxylative/Sonogashira-type cross-coupling using PdCl2(Cy*Phine)2
Authors: Yang Yong , Lim Yee Hwee , Robins Edward G. , Johannes Charles W.
Published: July 2016

Expedient protocol to access a wide range of internal alkynes and symmetrical di(heteroaryl)alkynesviatandem decarboxylative–Sonogashira cross-coupling.
Penicimutamides A–C: rare carbamate-containing alkaloids from a mutant of the marine-derived Penicillium purpurogenum G59
Authors: Li Chang-Wei , Wu Chang-Jing , Cui Cheng-Bin , Xu Lan-Lan , Cao Fei , Zhu Hua-Jie
Published: July 2016

Three new and rare carbamate-containing penicimutamides A–C (1–3) were discovered via activating silent pathways in a marine-derived fungus.
Effect of olefin and aromatics on thiophene adsorption desulfurization over modified NiY zeolites by metal Pd
Authors: Han Xiaona , Li Haizheng , Huang Haokai , Zhao Liang , Cao Liyuan , Wang Yuxian , Gao Jinsen , Xu Chunming
Published: July 2016

NiY and NiPdY adsorbents were prepared by incipient wetness impregnation and characterized by a series of characterization methods. Competitive adsorption desulfurization performance was evaluated in a fixed-bed flow reactor.
First-principles calculations of graphene-based polyaniline nano-hybrids for insight of electromagnetic properties and electronic structures
Authors: Duan Yuping , Liu Jin , Zhang Yahong , Wang Tongmin
Published: July 2016

The microwave dielectric properties of graphene-based polyaniline hybrids are studied based on experiments and first-principles calculation.
Nitrogen-rich MOF derived porous Co3O4/N–C composites with superior performance in lithium-ion batteries
Authors: Han Xiao , Chen Wen-Miao , Han Xiguang , Tan Yuan-Zhi , Sun Di
Published: July 2016

Porous Co3O4 fish-scale structures with N-doped carbon coating were successfully fabricated via a simple N-rich Co-MOF templated chemical transformation at 500 °C in a nitrogen atmosphere. The sample exhibited excellent electrochemical properties as an anode material for LIBs.
Biodegradable oxide synaptic transistors gated by a biopolymer electrolyte
Authors: Liu Rui , Zhu Li Qiang , Wang Wei , Hui Xiao , Liu Zhao Ping , Wan Qing
Published: July 2016

Green, biodegradable oxide synaptic transistors gated by biopolymer electrolytes were fabricated on a graphene coated PET substrate, mimicking several synaptic functions.
Amplitude Distributions of Cochlear Microphonic Response to an Acoustic Sinusoid in Noise
Authors: Teas Donald C. , Henry Gretchen B.
Published: July 2016

The distributions of instantaneous voltage amplitudes in the cochlear microphonic response recorded from a small segment along the basilar membrane are described by computing amplitude histograms. Comparisons are made between the distributions for noise and for those after the addition to the noise of successively stronger sinusoids. The amplitudes of the cochlear microphonic response to 5000 Hz low-pass noise are normally distributed in both Turn I and Turn III of the guinea pig’s cochlea. The spectral composition of the microphonic from Turn I and from Turn III resembles the output of band-pass filters set at about 4000 Hz, and about 500 Hz, respectively. The normal distribution of cochlear microphonic amplitudes for noise is systematically altered by increasing the strength of the added sinusoid. A decrease of three percent in the number of small amplitude events (±1 standard deviation) in the cochlear microphonic from Turn III is seen when the rms voltage of a 500 Hz sinusoid is at −18 dB re the rms voltage of the noise (at the earphone). When the rms of the sinusoid and noise are equal, the decrease in small voltages is about 25%, but there is also an increase in the number of large voltage amplitudes. Histograms were also computed for the output of an electronic filter with a pass-band similar to Turn III of the cochlea. Strong 500 Hz sinusoids showed a greater proportion of large amplitudes in the filter output than in CM
III
. The data are interpreted in terms of an anatomical substrate.