bluuebunny/crossref_metadata_2025 huggingface dataset:
Using genetic tools to estimate the prevalence of non‐native red deer (Cervus elaphus) in a Western European population
Authors: Frantz Alain C. , Zachos Frank E. , Bertouille Sabine , Eloy Marie‐Christine , Colyn Marc , Flamand Marie‐Christine
Published: August 2017

Game species like the red deer have been subjected to anthropogenic impacts for centuries. Translocations are often carried out—sometimes illegally—not only for sporting purposes, but also to increase trophy quality, reduce inbreeding, or mitigate bottlenecks after excessive persecution. Apart from the blurring of large‐scale genetic structure, translocations without adequate quarantine measure risk introducing pathogens into potentially immunologically naïve populations. It is therefore important to understand the frequency of clandestine translocations. Identification of non‐autochthonous animals and their potential origin is often difficult and, in red deer, has been hampered by the lack of large‐scale genotypic datasets for comparison. In the present study, we make use of a recently published European‐wide microsatellite dataset to detect and quantify the presence of non‐autochthonous red deer in a large population sample (n = 1,780) from Central Europe (Belgium). Using factorial correspondence analysis, assignment tests and Bayesian clustering algorithms we arrive at an estimate of 3.7% non‐autochthonous animals (or their descendants). Some of these animals were assigned to a nearby French population and may have immigrated into Belgium naturally, but the large majority must have been introduced by humans. Our analysis pointed to the British Isles and Germany/Poland as the potential origin of many introduced deer, regions known to have been source populations for translocations in Europe and beyond. We found evidence for recreational hunters using carcasses from farmed deer to fulfill mandatory hunting quotas. Our study is the first to quantify the extent of human‐mediated introductions in a European game species at such a large scale with large and representative sample sizes.
Inotropic myocardial reserve deficiency is the predominant feature of exercise haemodynamics in cardiac amyloidosis
Authors: Clemmensen Tor Skibsted , Mølgaard Henning , Sörensen Jens , Eiskjaer Hans , Andersen Niels Frost , Mellemkjaer Søren , Andersen Mads Jønsson , Tolbod Lars Poulsen , Harms Hendrik J. , Poulsen Steen Hvitfeldt
Published: August 2017

Aims

This study aimed to characterize invasive haemodynamics during exercise in subjects with cardiac amyloidosis (CA).

Methods and results

The study population numbered 44 subjects. Group A (CA‐positive, n = 24) comprised wild‐type transthyretin patients (n = 10), familial transthyretin amyloidosis mutation carriers (ATTRm) with cardiac involvement (n = 5), and light‐chain amyloidosis patients with cardiac involvement (n = 9). Group B (CA‐negative, n = 20) comprised four healthy ATTRm subjects without cardiac involvement documented by 11C‐PIB positron emission tomography and 16 healthy controls. All subjects underwent a symptom‐limited, semi‐supine exercise test with expired gas analysis and simultaneous right heart catheterization. CA patients had lower peak oxygen consumption [15 ± 6 mL/min/kg bodyweight (bwt) vs. 33 ± 7 mL/min/kg bwt; P < 0.0001] than controls. Myocardial reserve during exercise was significantly reduced in CA patients as reflected in a small increase in stroke volume index (SVI) and cardiac index (CI) compared with controls [ΔSVI: 4 mL/m2 (range: −1 to 8) vs. 14 mL/m2 (range: 5–25); P < 0.0001; ΔCI: 2 ± 2 L/min vs. 7 ± 2 L/min; P < 0.0001]. During exercise, CA patients had significantly higher left and right ventricular filling pressures than controls. Furthermore, CA patients had severely impaired pulmonary arterial compliance (PAC) compared with controls [2.9 mL/mmHg (range: 2.1–4.5) vs. 7.5 mL/mmHg (range: 5.7–10.4); P < 0.0001].

Conclusions

Cardiac amyloid deposits are associated with severely reduced inotropic myocardial reserve and increased left and right ventricular filling pressures during exercise. Furthermore, CA subjects have severely reduced PAC, which may contribute to right heart failure and reduced exercise capacity.
DNA damage in kidney transplant patients. Role of organ origin
Authors: Corredor Zuray , Rodríguez‐Ribera Lara , Coll Elisabet , Silva Irene , Díaz Juan Manuel , Ballarín José , Marcos Ricard , Pastor Susana
Published: August 2017

Chronic kidney disease (CKD) patients are characterized by elevated levels of genomic damage. This damage increases when kidney function decreases being maximum in hemodialysis patients. As kidney transplantation improves renal function, and it is related with better survival, the aim of our study was to evaluate potential changes in DNA damage levels after kidney transplantation, and comparing living donor recipients with cadaveric donor recipients. The alkaline comet assay was used to determine DNA breaks and oxidative damaged DNA; and the micronucleus assay was used to determine chromosomal breakage and/or aneuploidy. Fifty CKD patients were followed up after 6 and 12 months of their kidney transplantation. All patients increased their genomic damage levels after 6 and 12 months of renal transplantation, compared with those observed before transplantation, despite of the improvement of their metabolic functions. Donor advanced age correlated positively with higher DNA damage. Genomic damage was lower in living donor transplants with respect to cadaveric donor transplants. Our conclusion is that DNA damage increased in kidney transplantation patients, whereas their renal function improved. Higher levels of DNA damage were found in cadaveric donor transplants when compared to living donor transplants. Environ. Mol. Mutagen. 58:712–718, 2017. © 2017 Wiley Periodicals, Inc.
In vivo pig‐a and micronucleus study of the prototypical aneugen vinblastine sulfate
Authors: Avlasevich Svetlana L. , Labash Carson , Torous Dorothea K. , Bemis Jeffrey C. , MacGregor James T. , Dertinger Stephen D.
Published: August 2017

The Pig‐a assay is being used in regulatory studies to evaluate the potential of agents to induce somatic cell gene mutations and an OECD test guideline is under development. A working group involved with establishing the guideline recently noted that representative aneugenic agents had not been evaluated, and to help fill this data gap Pig‐a mutant phenotype and micronucleated reticulocyte frequencies were measured in an integrated study design to assess the mutagenic and cytogenetic damage responses to vinblastine sulfate exposure. Male Sprague Dawley rats were treated for twenty‐eight consecutive days with vinblastine dose levels from 0.0156 to 0.125 mg/kg/day. Micronucleated reticulocyte frequencies in peripheral blood were determined at Days 4 and 29, and mutant cell frequencies were determined at Days −4, 15, 29, and 46. Vinblastine affected reticulocyte frequencies, with reductions noted during the treatment phase and increases observed following cessation of treatment. Micronucleated reticulocyte frequencies were significantly elevated at Day 4 in the high dose group. Although a statistically significant increase in mutant reticulocyte frequencies were found for one dose group at a single time point (Day 46), it was not deemed biologically relevant because there was no analogous finding in mutant RBCs, it occurred at the lowest dose tested, and only 1 rat exceeded an upper bound tolerance interval established with historical negative control rats. Therefore, whereas micronucleus induction reflects vinblastine's well‐established aneugenic effect on hematopoietic cells, the lack of a Pig‐a response indicates that this tubulin‐binding agent does not cause appreciable mutagenicity in this same cell type. Environ. Mol. Mutagen. 59:30–37, 2018. © 2017 Wiley Periodicals, Inc.
Aberrant levels of SUV39H1 and SUV39H2 methyltransferase are associated with genomic instability in chronic lymphocytic leukemia
Authors: Carvalho Alves‐Silva Juliana , do Amaral Rabello Doralina , Oliveira Bravo Martha , Lucena‐Araujo Antônio , Madureira de Oliveira Diego , Morato de Oliveira Fábio , Magalhaes Rego Eduardo , Pittella‐Silva Fábio , Saldanha‐Araujo Felipe
Published: August 2017

Chromosomal alterations are commonly detected in patients with chronic lymphocytic leukemia (CLL) and impact disease pathogenesis, prognosis, and progression. Telomerase expression (hTERT), its activity and the telomere length are other important predictors of survival and multiple outcomes in CLL. SUV39H and SUV420H enzymes are histone methyltransferases (HMTases) involved in several cellular processes, including regulation of telomere length, heterochromatin organization, and genome stability. Here, we investigated whether SUV39H1, SUV39H2, SUV420H1, SUV420H2, and hTERT are associated with genomic instability of CLL. SUV39H (1/2), SUV420H (1/2), and hTERT expression was determined in 59 CLL samples by real time PCR. In addition, ZAP‐70 protein expression was evaluated by Flow Cytometry and patients’ karyotype was defined by Cytogenetic Analysis. Low expression of SUV39H1 was associated with the acquisition of altered and complex karyotypes. Conversely, high expression of SUV39H2 correlated with cytogenetic abnormalities in CLL patients. The pattern of karyotypic alterations differed in samples with detectable or undetectable hTERT expression. Furthermore, hTERT expression in CLL showed a correlation with transcript levels of SUV39H2, which, in part, can explain the association between SUV39H2 expression and cytogenetic abnormalities. Moreover, SUV39H1 correlated with SUV420H1 expression while SUV420H2 was associated with all other investigated HMTases. Our data show that the differential expression of SUV39H1 and SUV39H2 is associated with genomic instability and that the modulation of these HMTases can be an attractive approach to prevent CLL evolution. Environ. Mol. Mutagen. 58:654–661, 2017. © 2017 Wiley Periodicals, Inc.
The acute toxicity of major ion salts to Ceriodaphnia dubia. III. Mathematical models for mixture toxicity
Authors: Erickson Russell J. , Mount David R. , Highland Terry L. , Hockett J. Russell , Hoff Dale J. , Jenson Correne T. , Norberg-King Teresa J. , Peterson Kira N.
Published: August 2017

Based on previous research on the acute toxicity of major ions (Na+, K+, Ca2+, Mg2+, Cl–, SO42–, and HCO3–/CO32–) to Ceriodaphnia dubia, a mathematical model was developed for predicting the median lethal concentration (LC50) for any ion mixture, excepting those dominated by K-specific toxicity. One component of the model describes a mechanism of general ion toxicity to which all ions contribute and predicts LC50s as a function of osmolarity and Ca activity. The other component describes Mg/Ca-specific toxicity to apply when such toxicity exceeds the general ion toxicity and predicts LC50s as a function of Mg and Ca activities. This model not only tracks well the observed LC50s from past research used for model development but also successfully predicts LC50s from new toxicity tests on synthetic mixtures of ions emulating chemistries of various ion-enriched effluents and receiving waters. It also performs better than a previously published model for major ion toxicity. Because of the complexities of estimating chemical activities and osmolarity, a simplified model based directly on ion concentrations was also developed and found to provide useful predictions. Environ Toxicol Chem 2018;37:247–259. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Influence of physicochemical parameters on storage stability: Microbiological quality of fresh unpasteurized fruit juices
Authors: Kaddumukasa Phoebe P. , Imathiu Samuel M. , Mathara Julius M. , Nakavuma Jesca L.
Published: August 2017

Fresh juices rich in health and nutritional benefits are valued for their fresh flavor, taste, and aroma. These juices' quality however is affected by factors like temperature, light, and microbiological contamination significantly changing physicochemical parameters and storage stability. Physicochemical and microbiological analyses of passion fruit, pineapple, and mango juices in dark and light bottles at 24°C and 4°C were conducted in Kampala, Uganda for 12 days. Physicochemical parameters significantly reduced (p < .05) storage stability of fresh juices, while no significant changes (p > .05) were observed for the microbiological analyses. pH values ranged from 3.0 to 4.2 (dark) bottles and 2.9 to 4.0 (light) bottles for juices at 24°C and 4°C. °Brix values were from 1.0 to 5.5 for dark and clear bottles at 24°C and 4°C. TTA (%) values ranged from 1.1 to 7.2 (dark) bottles and 1.1 to 7.4 for (light) bottles at 24°C and 4°C. Ascorbic acid content ranged from 3.5 to 61.0 mg/ 100 ml and 5.5 to 56.7 mg/100 ml for juices in dark and clear bottles, respectively. total plate counts ranged from 1.3 × 10___ to 3.3 × 107 CFU/ml (dark bottles at 24°C) to 3.5 × 10³ to 3.3 × 108 CFU/ml (dark bottles at 4°C). For juices in light bottles, total plate counts ranged from 1.8 × 10___ to 8.0 × 107 CFU/ml (24°C) and 2.7 × 10___ to 1.5 × 108 CFU/ml (4°C). High microbial loads suggest the use of poor processing techniques and lack of good hygiene which lower quality and reduce storage stability of juices. Storage temperature greatly reduces physicochemical parameters both at ambient and refrigeration temperatures. This implies that temperature control for unpasteurized juices is critical in order to inhibit microorganism metabolic activities which accelerate biodeterioration leading to spoilage and short shelf life. Fresh unpasteurized juices stored at 24°C and 4°C may safely be consumed within 1 and 2 days, respectively.
Effect of processing methods on the nutritional content of three traditional vegetables leaves: Amaranth, black nightshade and jute mallow
Authors: Traoré Korotimi , Parkouda Charles , Savadogo Aly , Ba/Hama Fatoumata , Kamga Regine , Traoré Yves
Published: August 2017

The study assessed changes in nutritional content of some commonly consumed traditional vegetables subjected to postharvest processes. Amaranth (Amaranthus cruentus L.), black nightshade (Solanum scabrum Mill.) and jute mallow (Corchorus olitorius L.) leaves used as vegetables were subjected to blanching, boiling and drying. The proximate composition and β‐carotene content of fresh and processed leaves were determined. Amaranth, black nightshade and jute mallow leaves had 25.21%, 39.74% and 29.18% of protein, respectively. The β‐carotene levels were 16.40, 25.25 and 27.74 mg/100 g for black nightshade amaranth and jute mallow leaves, respectively. The ash content was 10.57% for black nightshade, 12.40% for jute mallow and 16.33% for amaranth. Processing methods caused decreases of β‐carotene and crude lipid content. Boiling for 30 min or more resulted in large loss of β‐carotene. Drying under shade resulted in less loss of β‐carotene than drying in cabinet at 50 and 60°C.
Effect of soy protein isolate on the functional, pasting, and sensory acceptability of cassava starch‐based custard
Authors: Akinwale Toyin E. , Shittu Taofik A. , Adebowale Abdul‐razaq A. , Adewuyi Sheriff , Abass Adebayo B.
Published: August 2017

Fortification of custard powder (CP) with protein from cheap sources such as soybean could potentially improve its nutritive value but may alter its functional and sensory properties. This study was therefore conducted to determine the effect of soy protein isolate (SPI) inclusion (0%–20%) on some functional and sensory properties of cassava starch‐based CP. Functional, pasting, and sensory acceptability were determined using standard methods. Increase in soy protein isolate significantly (p < .05) decreased dispersibility, packed bulk density, swelling power, peak, trough, breakdown, final, and setback viscosities, but increased least gelation concentration, water absorption capacity, and solubility index. This study further showed that despite increasing addition of SPI up to 20%, sensory acceptability of the cassava starch‐based CP formulations did not differ significantly, and most of them had very similar acceptability when compared to that of corn starch‐based CP.
Effects of cooking techniques on fatty acid and oxylipin content of farmed rainbow trout (Oncorhynchus mykiss)
Authors: Flaskerud Katrina , Bukowski Michael , Golovko Mikhail , Johnson LuAnn , Brose Stephen , Ali Ashrifa , Cleveland Beth , Picklo Matthew , Raatz Susan
Published: August 2017

The aim of this study was to investigate the effect of various cooking techniques on the fatty acid and oxylipin content of farmed rainbow trout. Rainbow trout is an excellent source of long‐chain omega‐3 (n‐3) polyunsaturated fatty acids (PUFA) which have beneficial health effects. Fillets of 2‐year‐old farmed rainbow trout were baked, broiled, microwaved, or pan‐fried in corn (CO), canola (CaO), peanut (PO), or high oleic sunflower oil (HOSO). Fatty acids and oxidized lipids were extracted from these samples and their respective raw fillet samples. Fatty acid content was determined using gas chromatography and oxylipin content by mass spectroscopy. The values obtained from each cooking method were compared to those obtained from the respective raw fillets using paired t tests. PUFA content was not altered when samples were baked, broiled, microwaved, or pan‐fried in CO or CaO. Pan‐frying in PO reduced α‐linolenic acid (18:3n‐3), eicosadienoic acid (20:2n‐6), and dihomo‐γ‐linolenic acid (20:3n‐6), while pan‐frying in HOSO reduced 18:3n‐3, eicosapentaenoic acid (20:5n‐3), docosapentaenoic acid (22:5n‐3), docosahexaenoic acid (22:6n‐3), linoleic acid (18:2n‐6), 18:3n‐6, 20:2n‐6, 20:3n‐6, docosatrienoic acid (22:2n‐6), and adrenic acid (22:4n‐6) compared to raw fish. Cooking decreased the omega‐6 (n‐6) PUFA‐derived oxylipins, but caused no change in 20:5n‐3 or 22:6n‐3‐derived oxylipins of the fillets. In conclusion, pan‐frying was the only cooking method to alter the fatty acid content of the fillets, while observed changes in oxylipin content varied by cooking method. As the physiological impact of oxylipins is currently unknown, these results suggest that the cooking methods which optimize the consumption of n‐3 PUFA from rainbow trout are baking, broiling, microwaving, or pan‐frying in CO, CaO, or PO.
Tetrahydrocurcumin ameliorates homocysteine‐mediated mitochondrial remodeling in brain endothelial cells
Authors: Vacek Jonathan C. , Behera Jyotirmaya , George Akash K. , Kamat Pradip K. , Kalani Anuradha , Tyagi Neetu
Published: August 2017

Homocysteine (Hcy) causes endothelial dysfunction by inducing oxidative stress in most neurodegenerative disorders. This dysfunction is highly correlated with mitochondrial dynamics such as fusion and fission. However, there are no strategies to prevent Hcy‐induced mitochondrial remodeling. Tetrahydrocurcumin (THC) is an anti‐inflammatory and anti‐oxidant compound. We hypothesized that THC may ameliorates Hcy‐induced mitochondria remodeling in mouse brain endothelial cells (bEnd3) cells. bEnd3 cells were exposed to Hcy treatment in the presence or absence of THC. Cell viability and autophagic cell death were measured with MTT and MDC staining assay. Reactive oxygen species (ROS) production was determined using DCFH‐DA staining by confocal microscopy. Autophagy flux was assessed using a conventional GFP‐microtubule‐associated protein 1 light chain 3 (LC3) dot assay. Interaction of phagophore marker LC‐3 with mitochondrial receptor NIX was observed by confocal imaging. Mitochondrial fusion and fission were evaluated by western blot and RT‐PCR. Our results demonstrated that Hcy resulted in cell toxicity in a dose‐dependent manner and supplementation of THC prevented the detrimental effects of Hcy on cell survival. Furthermore, Hcy also upregulated fission marker (DRP‐1), fusion marker (Mfn2), and autophagy marker (LC‐3). Finally, we observed that Hcy activated mitochondrial specific phagophore marker (LC‐3) and co‐localized with the mitochondrial receptor NIX, as viewed by confocal microscopy. Pretreatment of bEnd3 with THC (15 μM) ameliorated Hcy‐induced oxidative damage, mitochondrial fission/fusion, and mitophagy. Our studies strongly suggest that THC has beneficial effects on mitochondrial remodeling and could be developed as a potential therapeutic agent against hyperhomocysteinemia (HHcy) induced mitochondrial dysfunction.
Progress and prospects of circular RNAs in Hepatocellular carcinoma: Novel insights into their function
Authors: Hu Ji , Li Peng , Song Yang , Ge Yun‐xuan , Meng Xiao‐ming , Huang Cheng , Li Jun , Xu Tao
Published: August 2017

Hepatocellular carcinoma (HCC) is one of the most predominant subjects of liver malignancies, which arouses global concern in the recent years. Advanced studies have found that Circular RNAs (circRNAs) are differentially expressed in HCC, with its regulatory capacity in HCC pathogenesis and metastasis. However, the underlying mechanism remains largely unknown. In this review, we summarized the functions and mechanisms of those aberrantly expressed circRNAs in HCC tissues. We hope to enlighten more comprehensive studies on the detailed mechanisms of circRNAs and explore their potential values in clinic applications. It revealed that hsa_circ_0004018 can be used as a potential biomarker in HCC diagnosis, with its superior sensitivity to alpha‐fetoprotein (AFP). Notably, the correlation of circRNA abundance in the proliferation of liver regeneration (LR) has recently been clarified and different circRNA profiles served as candidates for nonalcoholic steatohepatitis (NASH) diagnosis also be discussed. Therefore, the improved understanding of circRNAs in HCC pathogenesis and metastasis proposed a novel basis for the early diagnosis in HCC patients, which provides a useful resource to explore the pathogenesis of HCC.
Development of the LYVE‐1 gene with an acidic‐amino‐acid‐rich (AAAR) domain in evolution is associated with acquisition of lymph nodes and efficient adaptive immunity
Authors: Huang Shuan Shian , Li Ya‐Wen , Wu Jen‐Leih , Johnson Frank E. , Huang Jung San
Published: August 2017

CRSBP‐1 (mammalian LYVE‐1) is a membrane glycoprotein highly expressed in lymphatic endothelial cells (LECs). It has multiple ligands, including hyaluronic acid (HA) and growth factors/cytokines (e.g., PDGF‐BB and VEGF‐A) containing CRS motifs (clusters of basic amino‐acid residues). The ligand binding activities are mediated by Link module and acidic‐amino‐acid‐rich (AAAR) domains, respectively. These CRSBP‐1/LYVE‐1 ligands have been shown to induce opening of lymphatic intercellular junctions in LEC monolayers and in lymphatic vessels in wild‐type mice. We hypothesize that CRSBP‐1/LYVE‐1 ligands, particularly CRS‐containing growth factors/cytokines, are secreted by immune and cancer cells for lymphatic entry during adaptive immune responses and lymphatic metastasis. We have looked into the origin of the Link module and AAAR domain of LYVE‐1 in evolution and its association with the development of lymph nodes and efficient adaptive immunity. Lymph nodes represent the only major recent innovation of the adaptive immune systems in evolution particularly to mammals and bird. Here we demonstrate that the development of the LYVE‐1 gene with the AAAR domain in evolution is associated with acquisition of lymph nodes and adaptive immunity. LYVE‐1 from other species, which have no lymph nodes, lack the AAAR domain and efficient adaptive immunity. Synthetic CRSBP‐1 ligands PDGF and VEGF peptides, which contain the CRS motifs of PDGF‐BB and VEGF‐A, respectively, specifically bind to CRSBP‐1 but do not interact with either PDGFβR or VEGFR2. These peptides function as adjuvants by enhancing adaptive immunity of pseudorabies virus (PRV) vaccine in pigs. These results support the notion that LYVE‐1 is involved in adaptive immunity in mammals.
Heparan sulfate proteoglycan deficiency up‐regulates the intracellular production of nitric oxide in Chinese hamster ovary cell lines
Authors: Lucena Sheyla V. , Moura Gioconda E. D. D. , Rodrigues Tiago , Watashi Carolina M. , Melo Fabiana H. , Icimoto Marcelo Y. , Viana Gustavo M. , Nader Helena B. , Monteiro Hugo P. , Tersariol Ivarne L. S. , Ogata Fernando T.
Published: August 2017

We investigated the role of glycosaminoglycans (GAGs) in the regulation of endothelial nitric oxide synthase (eNOS) activity in wild‐type CHO‐K1 cells and in xylosyltransferase‐deficient CHO‐745 cells. GAGs inhibit the integrin/FAK/PI3K/AKT signaling pathway in CHO‐K1 cells, decreasing the phosphorylation of eNOS at Ser1177. Furthermore, in CHO‐K1 cells, eNOS and PKCα are localized at sphingolipid‐ and cholesterol‐rich domains in the plasma membrane called caveolae. At caveolae, PKCα activation stimulates the phosphorylation of eNOS on Thr495, resulting in further inhibition of NO production in these cells. In our data, CHO‐745 cells generate approximately 12‐fold more NO than CHO‐K1 cells. Increased NO production in CHO‐745 cells promotes higher rates of protein S‐nitrosylation and protein tyrosine nitration. Regarding reactive oxygen species (ROS) production, CHO‐745 cells show lower basal levels of superoxide (O2−) than CHO‐K1 cells. In addition, CHO‐745 cells express higher levels of GPx, Trx1, and catalase than CHO‐K1 cells, suggesting that CHO‐745 cells are in a constitutive nitrosative/oxidative stress condition. Accordingly, we showed that CHO‐745 cells are more sensitive to oxidant‐induced cell death than CHO‐K1 cells. The high concentration of NO and reactive oxygen species generated by CHO‐745 cells can induce simultaneous mitochondrial biogenesis and antioxidant gene expression. These observations led us to propose that GAGs are part of a regulatory mechanism that participates in eNOS activation and consequently regulates nitrosative/oxidative stress in CHO cells.
Syntheses of isotope‐labeled SGLT2 inhibitor canagliflozin (JNJ‐28431754)
Authors: Lin Ronghui , Hoerr David C. , Weaner Larry E. , Salter Rhys
Published: August 2017

Canagliflozin (Invokana, JNJ‐28431754) is an orally bioavailable and selective SGLT2 (subtype 2 sodium‐glucose transport protein) inhibitor approved for the treatment of type 2 diabetes. Herein, we report the synthesis of 13C and 14C‐labeled canagliflozin. Stable isotope‐labeled [13C6]canagliflozin was synthesized in 4 steps starting from [13C6]‐labeled glucose. The [14C]‐Labeled canagliflozin was synthesized by incorporation of [14C] into the benzylic position between the thiophene and benzene rings of the compound. Detailed synthesis of the isotope‐labeled compounds is reported.
The Genius Dilemma: Fortune 1000 CEO Personality and Firm Innovation
Authors: Gal David
Published: August 2017

Innovation is important to organizations’ long‐lasting success, yet many organizations fail to successfully promote innovation. One factor likely to bear an important influence on whether an organization successfully innovates, but that has received relatively little research attention, is the personality of the CEO. The present research examines the link between the personality of the CEO and product and service innovation in the firm using a unique sample of Fortune 1000 CEO's. Results show that conscientiousness in the CEO negatively predicts the level of innovation in the firm. Moreover, this relationship is evident among CEO's who have filled the CEO role for at least 3 years, but not among CEO's who have filled the CEO role for less than 3 years.
GC–MS/MS method for the determination and pharmacokinetic analysis of borneol and muscone in rat after the intravenous administration of Xingnaojing injection
Authors: Song Yunfei , Chu Yang , Ma Xiaohui , Zheng Haoran , Bai Xiaolin , Zhou Shuiping , Yu Boyang
Published: August 2017

A simple and sensitive gas chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of borneol and muscone in rat plasma. The analytes and internal standard, naphthalene, were extracted using a convenient one‐step liquid–liquid extraction method with ethyl acetate. The chromatographic separation was realized on a HP‐5MS capillary column and detected in multiple reaction monitoring mode. Excellent linearity (R2 ≥ 0.996) was shown over 10.0–5000 ng/mL for borneol and 2.5–250 ng/mL for muscone. The lower limit of quantitation was 10 and 2.5 ng/mL for borneol and muscone, respectively. The intra‐ and interday precisions were less than 7.52%, and the accuracy values were between  −8.03 and 14.52%. The extraction recovery, matrix effect, and stability were sufficient to meet the Food and Drug Administration criteria. Meanwhile, the assay was successfully applied to the preclinical pharmacokinetic study of borneol and muscone following intravenous administration of Xingnaojing injection, a modern Chinese herbal medicine preparation.
Metformin incombination with curcumin inhibits the growth, metastasis, and angiogenesis of hepatocellular carcinoma in vitro and in vivo
Authors: Zhang Hui‐Hui , Zhang Ying , Cheng Yan‐Na , Gong Fu‐Lian , Cao Zhan‐Qi , Yu Lu‐Gang , Guo Xiu‐Li
Published: August 2017

Hepatocellular carcinoma (HCC) has poor prognosis due to the advanced disease stages by the time it is diagnosed, high recurrence rates and metastasis. In the present study, we investigated the effects of metformin (a safe anti‐diabetic drug) and curcumin (a turmeric polyphenol extracted from rhizome of Curcuma longa Linn.) on proliferation, apoptosis, invasion, metastasis, and angiogenesis of HCC in vitro and in vivo. It was found that co‐treatment of metformin and curcumin could not only induce tumor cells into apoptosis through activating the mitochondria pathways, but also suppress the invasion, metastasis of HCC cells and angiogenesis of HUVECs. These effects were associated with downregulation of the expression of MMP2/9, VEGF, and VEGFR‐2, up‐regulation of PTEN, P53 and suppression of PI3K/Akt/mTOR/NF‐κB and EGFR/STAT3 signaling. Co‐administration of metformin and curcumin significantly inhibited HCC tumor growth than administration with metformin or curcumin alone in a xenograft mouse model. Thus, metformin and curcumin in combination showed a better anti‐tumor effects in hepatoma cells than either metformin or curcumin presence alone and might represent an effective therapeutic strategy for HCC treatment.
Na/K‐ATPase regulates bovine sperm capacitation through raft‐ and non‐raft‐mediated signaling mechanisms
Authors: Rajamanickam Gayathri D. , Kastelic John P. , Thundathil Jacob C.
Published: August 2017

Highly dynamic lipid microdomains (rafts) in the sperm plasma membrane contain several signaling proteins that regulate sperm capacitation. Na/K‐ATPase isoforms (testis‐specific isoform ATP1A4 and ubiquitous isoform ATP1A1) are abundant in bovine sperm plasma membrane. We previously reported that incubation of bovine sperm with ouabain, a specific Na/K‐ATPase ligand, induced tyrosine phosphorylation of several sperm proteins during capacitation. The objective of this study was to investigate the roles of lipid rafts and non‐rafts in Na/K‐ATPase enzyme activity and signaling during bovine sperm capacitation. Content of ATP1A4 and, to a lesser extent, ATP1A1 was increased in raft and non‐raft fractions of capacitated sperm, although non‐raft enzyme activities of both isoforms were higher than the corresponding activities in rafts from capacitated sperm. Yet, ATP1A4 was the predominant isoform responsible for total Na/K‐ATPase activity in both rafts and non‐rafts. A comparative increase in phosphorylation of signaling molecules was observed in both raft (CAV1) and non‐raft (EGFR and ERK1/2) membrane fractions during capacitation. Although SRC was phosphorylated in both membrane fractions, the non‐raft fraction possessed more of this activated form. We also inferred, by immunoprecipitation, that ATP1A4 interacted with CAV1 and EGFR in the raft fraction, whereas interactions of ATP1A4 with SRC, EGFR, and ERK1/2 occurred in the non‐raft fraction of ouabain‐capacitated sperm; conversely, ATP1A1 interacted only with CAV1 in both fractions of uncapacitated and capacitated sperm. In conclusion, both raft and non‐raft cohorts of Na/K‐ATPase isoforms contributed to phosphorylation of signaling molecules during bovine sperm capacitation.
Selective swelling blends of block copolymers for nanoporous membranes with enhanced permeability and robustness
Authors: Wang Zhaogen , Liu Rui , Lan Qianqian , Wang Yong
Published: August 2017

Block copolymers (BCPs) are important precursors to produce membranes with well‐defined porosities. However, it remains challenging to prepare robust and affordable BCP‐based membranes. In this work, cheap commodity styrene‐butadiene‐styrene (SBS) elastic triblock copolymers are mixed with polystyrene‐block‐poly (2‐vinylpyridine) (SV) block copolymers in solutions, leading to macroscopically stable blend films upon casting because of the compatibilizer effect of PS existing in both copolymers. By soaking the blend films in ethanol, the microdomains of poly(2‐vinylpyridine) are selectively swollen and cavitated upon drying, resulting in a hierarchical structure with perforated SV phases interwoven with the SBS phases. The blend membranes with 30% SBS exhibit improved water permeability and mechanical robustness due to the presence of elastic SBS compared to neat SV membranes; meanwhile, the rejections of the blend membranes remain largely unchanged. Moreover, the blend membranes exhibit a pH‐responsive function, and homoporous SV regions are obtained by pre‐aligning the SV phases. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1617–1625
Water‐soluble top coats for orientation control of liquid crystal‐containing block copolymer films
Authors: Xie He‐Lou , Li Xiao , Suh Hyo Seon , Ren Jia‐Xing , Wan Ling‐Shu , Craig Gordon S. W. , Arges Christopher G. , Nealey Paul F.
Published: August 2017

An easily removable, water‐soluble top coat of polyvinylpyrrolidone (PVP) is used to control the orientation of microdomains in a liquid crystalline block copolymer (LC BCP, poly(ethylene oxide)‐block‐poly(6‐(4‐methoxy‐azobenzene‐4′‐butyl) hexyl methacrylate)). The corresponding LC homopolymer is also investigated for comparison. Atomic force microscopy is used to determine the orientation of the cylindrical microdomains of the LC BCP. UV–vis spectroscopy and grazing incidence wide‐angle X‐ray scattering are used to determine the orientation of the LC mesogens in the LC homopolymer and the LC BCP films annealed both with and without a top coat. Once the LC BCP morphology is self‐assembled, the PVP top coat layer can be easily removed with water or alcohol. The facile removal of the top coat improves the processability of BCPs in technological applications, and enables direct investigation of the BCP morphology in scientific studies. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1569–1574
A large‐scale expression strategy for multimeric extracellular protein complexes using Drosophila S2 cells and its application to the recombinant expression of heterodimeric ligand‐binding domains of taste receptor
Authors: Yamashita Atsuko , Nango Eriko , Ashikawa Yuji
Published: August 2017

Many of the extracellular proteins or extracellular domains of plasma membrane proteins exist or function as homo‐ or heteromeric multimer protein complexes. Successful recombinant production of such proteins is often achieved by co‐expression of the components using eukaryotic cells via the secretory pathway. Here we report a strategy addressing large‐scale expression of hetero‐multimeric extracellular domains of plasma membrane proteins and its application to the extracellular domains of a taste receptor. The target receptor consists of a heterodimer of T1r2 and T1r3 proteins, and their extracellular ligand binding domains (LBDs) are responsible for the perception of major taste substances. However, despite the functional importance, recombinant production of the heterodimeric proteins has so far been unsuccessful. We achieved the successful preparation of the heterodimeric LBD by use of Drosophila S2 cells, which have a high secretory capacity, and by the establishment of a stable high‐expression clone producing both subunits at a comparable level. The method overcame the problems encountered in the conventional transient expression of the receptor protein in insect cells using baculovirus or vector lipofection, which failed in the proper heterodimer production because of the biased expression of T1r3LBD over T1r2LBD. The large‐scale expression methodology reported here may serve as one of the considerable strategies for the preparation of multimeric extracellular protein complexes.
Charge neutralization in the active site of the catalytic trimer of aspartate transcarbamoylase promotes diverse structural changes
Authors: Endrizzi James A. , Beernink Peter T.
Published: August 2017

A classical model for allosteric regulation of enzyme activity posits an equilibrium between inactive and active conformations. An alternative view is that allosteric activation is achieved by increasing the potential for conformational changes that are essential for catalysis. In the present study, substitution of a basic residue in the active site of the catalytic (C) trimer of aspartate transcarbamoylase with a non‐polar residue results in large interdomain hinge changes in the three chains of the trimer. One conformation is more open than the chains in both the wild‐type C trimer and the catalytic chains in the holoenzyme, the second is closed similar to the bisubstrate‐analog bound conformation and the third hinge angle is intermediate to the other two. The active‐site 240s loop conformation is very different between the most open and closed chains, and is disordered in the third chain, as in the holoenzyme. We hypothesize that binding of anionic substrates may promote similar structural changes. Further, the ability of the three catalytic chains in the trimer to access the open and closed active‐site conformations simultaneously suggests a cyclic catalytic mechanism, in which at least one of the chains is in an open conformation suitable for substrate binding whereas another chain is closed for catalytic turnover. Based on the many conformations observed for the chains in the isolated catalytic trimer to date, we propose that allosteric activation of the holoenzyme occurs by release of quaternary constraint into an ensemble of active‐site conformations.
Does It Get Better? Recent Estimates of Sexual Orientation and Earnings in the United States
Authors: Carpenter Christopher S. , Eppink Samuel T.
Published: August 2017

Using 2013–2015 National Health Interview Survey data, we reproduce a well‐documented finding that self‐identified lesbians earn significantly more than comparable heterosexual women. These data also show—for the first time in the literature—that self‐identified gay men also earn significantly more than comparable heterosexual men, a difference on the order of 10% of annual earnings. We discuss several possible explanations for the new finding of a gay male earnings premium and suggest that reduced discrimination and changing patterns of household specialization are unlikely to be the primary mechanisms.
Collaborative Planning in Process: An Ethnomethodological Perspective
Authors: Lee Josephine , Burch Alfred Rue
Published: August 2017

Following Ellis's () call for more social and process‐oriented planning research, this study explores how learners approach collaborative planning tasks in the classroom as a locally contingent activity in situ. Drawing on ethnomethodology and conversation analysis, the present study focuses on a group planning stage that precedes the final task of delivering a presentation. Fine‐grained analyses of the interaction reveal that group planning is essentially a nonlinear, social, and pragmatic activity wherein the students manage participant roles, resolve disputes and misunderstandings, and collectively work toward effective task completion. These findings highlight that, although the groups begin with the same task‐as‐workplan (Breen, ; Seedhouse, ), the students’ concerns are driven by locally constructed goals and plans‐in‐process, and as they work toward a group consensus they are required to deal with a wide range of social and interactional contingencies.
The system capacity view of aging and longevity
Authors: Han Jing‐Dong J. , Hou Lei , Sun Na , Xu Chi , McDermott Joseph , Wang Dan
Published: August 2017

Background

Aging is a complex systems level problem that needs a systems level solution. However, system models of aging and longevity, although urgently needed, are still lacking, largely due to the paucity of conceptual frameworks for modeling such a complex process.

Results

We propose that aging can be viewed as a decline in system capacity, defined as the maximum level of output that a system produces to fulfill demands. Classical aging hallmarks and anti‐aging strategies can be well‐aligned to system capacity. Genetic variants responsible for lifespan variation across individuals or species can also be explained by their roles in system capacity. We further propose promising directions to develop systems approaches to modulate system capacity and thus extend both healthspan and lifespan.

Conclusions

The system capacity model of aging provides an opportunity to examine aging at the systems level. This model predicts that the extent to which aging can be modulated is normally limited by the upper bound of the system capacity of a species. Within such a boundary, aging can be delayed by moderately increasing an individual’s system capacity. Beyond such a boundary, increasing the upper bound is required, which is not unrealistic given the unlimited potential of regenerative medicine in the future, but it requires increasing the capacity of the whole system instead of only part of it.
Models, methods and tools for ancestry inference and admixture analysis
Authors: Yuan Kai , Zhou Ying , Ni Xumin , Wang Yuchen , Liu Chang , Xu Shuhua
Published: August 2017

Background

Genetic admixture refers to the process or consequence of interbreeding between two or more previously isolated populations within a species. Compared to many other evolutionary driving forces such as mutations, genetic drift, and natural selection, genetic admixture is a quick mechanism for shaping population genomic diversity. In particular, admixture results in “recombination” of genetic variants that have been fixed in different populations, which has many evolutionary and medical implications.

Results

However, it is challenging to accurately reconstruct population admixture history and to understand of population admixture dynamics. In this review, we provide an overview of models, methods, and tools for ancestry inference and admixture analysis.

Conclusions

Many methods and tools used for admixture analysis were originally developed to analyze human data, but these methods can also be directly applied and/or slightly modified to study non‐human species as well.
Double Jeopardy Benchmarks for Political Polls
Authors: Kooyman Caitlin , Wright Malcolm J.
Published: August 2017

Consumer goods marketers often benchmark brand performance against known patterns of consumer loyalty, such as the law of double jeopardy. This law states that lesser known brands suffer twice; fewer people buy them, and those that do like them less and are less loyal. Unless double jeopardy effects are understood the performance of a small brand may be misinterpreted as poor when it is in fact normal for a brand of that size. Political opinion polls also show double jeopardy effects, although the evidence base remains thin. We provide fresh evidence of double jeopardy in political opinion polls in a New Zealand context, and show how to benchmark politicians’ performance against the double jeopardy line. We discuss insights arising from this new method of analyzing political performance.
How Do Psychological Risk Factors Predict Sexual Outcomes? A Comparison of Four Models of Young Women’s Sexual Outcomes
Authors: Tutino Jessica S. , Ouimet Allison J. , Shaughnessy Krystelle
Published: August 2017

Background

Recent research findings suggest that women who report high anxiety sensitivity (AS; the fear of physiologic sensations associated with anxiety) also report increased sexual dysfunction and decreased sexual satisfaction. Moreover, findings suggest that maladaptive emotion regulation (ER) can contribute to the relation between AS and psychological distress, thereby indirectly influencing sexual outcomes. Identifying relations among these variables and how they specifically relate to sexual outcomes could be vital for diagnostic and therapeutic purposes. As such, a comparison of different models of sexual outcomes that encompass psychological and sexual risk factors is needed.

Aim

To compare four psychological models of women’s sexual outcomes in a cross-sectional sample and specifically to investigate whether psychological factors (ie, AS, ER, psychological distress) uniquely or jointly predict related, but distinct, sexual outcomes in women: sexual functioning, sexual quality of life, and frequency of sexual activity.

Methods

Women (N = 316) completed an online survey that included the Anxiety Sensitivity Index–3, Difficulties with Emotion Regulation Scale, Depression Anxiety Stress Scales, Sexual Quality of Life Scale–Female, Female Sexual Function Index, and Sexual Experiences Questionnaire–Female.

Outcomes

Outcome variables included women’s self-reported sexual functioning, sexual quality of life, and frequency of sexual activity.

Results

Path analysis models demonstrated that psychological factors predicted orgasm, sexual pain, sexual quality of life, and frequency of partnered sexual activity in women but predicted sexual desire, arousal, lubrication, and frequency of solitary sexual activity to a lesser degree. We found that ER significantly accounted for the relation between AS and psychological distress through mediation and moderation pathways.

Clinical Translation

Clinicians would benefit from incorporating psychological risk factors in their assessment and interventions of women’s sexual concerns.

Strengths and Limitations

This is the first study to compare models of women’s sexual lives using indicators of mental and sexual health. However, our study was limited to a cross-sectional sample of young women in one university setting.

Conclusions

AS, ER, and psychological distress are related to sexual functioning, sexual quality of life, and frequency of partnered sexual activity in young women. Psychological risk factors should be taken into consideration to better understand women’s sexual lives.