bluuebunny/crossref_metadata_2025 huggingface dataset:
PD‐1 regulates extrathymic regulatory T‐cell differentiation
Authors: Chen Xiufen , Fosco Dominick , Kline Douglas E. , Meng Liping , Nishi Saki , Savage Peter A. , Kline Justin
Published: June 2014

Treg cells and the programed death‐1/programed death ligand‐1 (PD‐1/PD‐L1) pathway are both critical for maintaining peripheral tolerance to self‐Ags. A significant subset of Treg cells constitutively expresses PD‐1, which prompted an investigation into the role of PD‐1/PD‐L1 interactions in Treg‐cell development, function, and induction in vivo. The phenotype and abundance of Treg cells was not significantly altered in PD‐1‐deficient mice. The thymic development of polyclonal and monospecific Treg cells was not negatively impacted by PD‐1 deficiency. The suppressive function of PD‐1−/− Treg cells was similar to their PD‐1+/+ counterparts both in vitro and in vivo. However, in three different in vivo experimental settings, PD‐1−/− conventional CD4+ T cells demonstrated a strikingly diminished tendency toward differentiation into peripherally induced Treg (pTreg) cells. Our results demonstrate that PD‐1 is dispensable for thymic Treg‐cell development and suppressive function, but is critical for the extrathymic differentiation of pTreg cells in vivo. These data suggest that Ab blockade of the PD‐1/PD‐L1 pathway may augment T‐cell responses by acting directly on conventional T cells, and also by suppressing the differentiation of pTreg cells.
European consensus proposal for immunoglobulin therapies
Authors: Sewell W. A. Carrock , Kerr Jacqueline , Behr‐Gross Marie‐Emmanuelle , Peter Hans‐Hartmut ,   on behalf of the Kreuth Ig Working Group
Published: June 2014

The use of immunoglobulin (Ig) preparations (intravenous, IVIg, subcutaneous, SCIg) for replacement and immunomodulation therapy worldwide has tripled in the past 20 years and represents an ever‐increasing cost factor for healthcare organizations. The limited access to the starting material of this essential medicinal product is currently the driving force for human plasma collection. Increasing awareness and improved diagnosis of human primary immunodeficiencies and a broadening of immunomodulatory indications are responsible for this development, and on a longer run might lead to plasma supply shortages. Consensus recommendations for the optimal use of Ig in clinical practice, including priority rankings for the most urgent indications, are therefore urgently needed. During a recent meeting in Kreuth, Germany, expert nominees from 36 Council of Europe states, together with colleagues from observer countries and regulatory agencies came up with this consensus statement.

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STAT of the union: Dynamics of distinct tumor‐associated macrophage subsets governed by STAT1
Authors: Van Overmeire Eva , Laoui Damya , Keirsse Jiri , Bonelli Stefano , Lahmar Qods , Van Ginderachter Jo A.
Published: June 2014

The tumor stroma has long been ignored as therapeutic target, but it has become clear that several stromal cell types play a nonredundant role during tumor progression. In particular, macrophages possess the capacity to stimulate tumor growth and metastasis via multiple mechanisms. In this issue of the European Journal of Immunology, a study by Tymoszuk et al. Eur. J. Immunol. 2014. 44: 2247–2262 demonstrates that both monocyte recruitment and local macrophage proliferation determines the tumor‐associated macrophage (TAM) pool size in HER2/Neu‐driven mammary carcinomas. These tumors contain two main TAM subsets—MHC class II (MHC‐II)loF4/80hi and MHC‐IIhiF4/80lo—similar to what was observed in other tumor models. Interestingly, only the MHC‐IIloF4/80hi subset is largely absent in a STAT1‐deficient background. STAT1 induces the expression of CSF‐1, which in turn drives TAM proliferation and possibly also the M2 gene signature of MHC‐IIloF4/80hi TAM. Conversely, STAT1 deficiency upregulates M2 gene expression in MHC‐IIhiF4/80lo TAM, demonstrating that both TAM subsets are differentially regulated, probably as a consequence of their distinct intratumoral localization. In this Commentary, we place these findings in the context of current knowledge and propose new avenues for future research.
Concurrent evaluation of general, immune, and genetic toxicity endpoints as part of an integrated testing strategy
Authors: Schisler Melissa R. , Sura Radhakrishna , Visconti Nicolo R. , Sosinski Lindsay K. , Murphy Lynea A. , LeBaron Matthew J. , Boverhof Darrell R.
Published: June 2014

Integrated testing strategies involve the assessment of multiple endpoints within a single toxicity study and represent an important approach for reducing animal use and streamlining testing. The present study evaluated the ability to combine general, immune, and genetic toxicity endpoints into a single study. Specifically, this study evaluated the impact of sheep red blood cell (SRBC) immunization, as part of the T‐cell dependent antibody response (TDAR) assay, on organ weights, micronuclei (MN) formation (bone marrow and peripheral blood), and the Comet assay response in the liver of female F344/DuCrl rats treated with cyclophosphamide (CP) a known immunosuppressive chemical and genotoxicant. For the TDAR assay, treatment with CP resulted in a dose‐dependent decrease in the antibody response with a suppression of greater than 95% at the high dose. Injection with SRBC had no impact on evaluated organ weights, histopathology, hematology, and clinical chemistry parameters. Analysis of MN formation in bone marrow and peripheral blood revealed a dose‐dependent increase in response to CP treatment. Injection with SRBC had no impact on the level of MN in control animals and did not alter the dose response of CP. There was a slight increase in liver DNA damage in response to CP as measured by the Comet assay; however, injection with SRBCs did not alter this endpoint. Overall these data provide strong support for the concurrent assessment of general, immune, and genetic toxicology endpoints within a single study as part of an integrated testing strategy approach. Environ. Mol. Mutagen. 55:530–541, 2014. © 2014 Wiley Periodicals, Inc.
Temporo‐frontal functional connectivity during auditory change detection is altered in Alzheimer's disease
Authors: Hsiao Fu‐Jung , Chen Wei‐Ta , Wang Pei‐Ning , Cheng Chia‐Hsiung , Lin Yung‐Yang
Published: June 2014

Cortico‐cortical connections might be disturbed in patients with Alzheimer's disease (AD). This study aimed to investigate the alterations of functional connectivity in AD during auditory change detection processing by measuring the local neuronal activation and functional connectivity between cortical regions. Magnetoencephalographic responses to deviant and standard sounds were recorded in 16 AD patients, 18 young controls and 16 elderly controls. Larger source amplitudes and shorter peak latencies were found in the right temporal magnetic mismatch responses of young controls compared with elderly controls and AD patients. During deviant stimuli, the right theta temporal‐frontal phase synchrony was significantly smaller in AD than in young controls and elderly controls. Moreover, the left temporal‐frontal synchronization at theta and alpha bands was reduced in AD and elderly controls compared with young controls. In conclusion, the loss in temporo‐frontal theta synchronization might be an electrophysiological hallmark of AD. Hum Brain Mapp 35:5565–5577, 2014. © 2014 Wiley Periodicals, Inc.
Synthesis and Cyclization Reactions of Axially Chiral N‐Sulfamoyl‐acrylamidines
Authors: Lender Andreas , Tornus Ingo , Hübner Eike , Schaumann Ernst
Published: June 2014

N‐Sulfonylamines are generated and in situ reacted with 3‐dialkylamino‐2H‐azirines to give N‐sulfamoyl‐acrylamidines. The magnetic nonequivalence of prochiral groups in the 1H NMR spectrum suggests an axially chiral structure, which is supported by density‐functional theory calculations. Base‐induced cyclization occurs readily to give 1,2,6‐thiadiazine derivatives.
Regioselective Nucleophilic Substitution of 5‐Bromo‐2‐methoxytropone
Authors: Sato Ohki , Nitta Ai , Yamamoto Ami
Published: June 2014

The reaction of 5‐bromo‐2‐methoxytropone with O‐ and N‐nucleophiles, such as ethanol/potassium carbonate, sodium hydroxide, diethylamine, propylamine, p‐chloroaniline/triethylamine, and p‐phenylenediamine/triethylamine, gave corresponding 2‐O‐ and 2‐N‐substituted troponoids. Alkyl diamines reacted with the substrate to produce bis(2‐aminotropone)s. In the case of S‐nucleophiles as 1‐propanethiol, thiophenol, and 4‐aminothiophenol with a base, the regioselective substitution at the 5‐position occurred. Halogenation reagents, triphenyldibromophosphorane and its dichloro analogue, furnished 2,5‐dibromo‐ and 2,5‐dichlorotropones, respectively.
Developmental topographical disorientation and decreased hippocampal functional connectivity
Authors: Iaria Giuseppe , Arnold Aiden E.G.F. , Burles Ford , Liu Irene , Slone Edward , Barclay Sarah , Bech‐Hansen Torben N. , Levy Richard M.
Published: June 2014

Developmental topographical disorientation (DTD) is a newly discovered cognitive disorder in which individuals experience a lifelong history of getting lost in both novel and familiar surroundings. Recent studies have shown that such a selective orientation defect relies primarily on the inability of the individuals to form cognitive maps, i.e., mental representations of the surrounding that allow individuals to get anywhere from any location in the environment, although other orientation skills are additionally affected. To date, the neural correlates of this developmental condition are unknown. Here, we tested the hypothesis that DTD may be related to ineffective functional connectivity between the hippocampus (HC; known to be critical for cognitive maps) and other brain regions critical for spatial orientation. A group of individuals with DTD and a group of control subjects underwent a resting‐state functional magnetic resonance imaging (rsfMRI) scan. In addition, we performed voxel‐based morphometry to investigate potential structural differences between individuals with DTD and controls. The results of the rsfMRI study revealed a decreased functional connectivity between the right HC and the prefrontal cortex (PFC) in individuals with DTD. No structural differences were detected between groups. These findings provide evidence that ineffective functional connectivity between HC and PFC may affect the monitoring and processing of spatial information while moving within an environment, resulting in the lifelong selective inability of individuals with DTD to form cognitive maps that are critical for orienting in both familiar and unfamiliar surroundings. © 2014 Wiley Periodicals, Inc.
An Allais paradox without mental time travel
Authors: Craver Carl F. , Cova Florian , Green Leonard , Myerson Joel , Rosenbaum R. Shayna , Kwan Donna , Bourgeois‐Gironde Sacha
Published: June 2014

The capacity to anticipate future experiences of regret has been hypothesized to explain otherwise irrational aspects of human decision‐making, including the certainty effect (Kahneman and Tversky (1979) Econometrica 47:263–291) and the common ratio effect (Allais (1953) Econometrica 21:503–546). The anticipated regret hypothesis predicts that individuals incapable of episodically imagining their personal futures, as has been reported for people with extensive damage to medial temporal lobe structures and resulting deficits in episodic thought, should be immune to these effects. We report that K.C., who has extensive bilateral damage to his hippocampus and adjacent medial temporal lobe structures and nearly complete deficits in his ability to episodically imagine his personal future, nonetheless displays both the certainty and the common ratio effects. These results suggest that the episodic anticipation of future regret does not explain the general human tendency to display the certainty and common ratio effects. © 2014 Wiley Periodicals, Inc.
Activity‐based anorexia during adolescence disrupts normal development of the CA1 pyramidal cells in the ventral hippocampus of female rats
Authors: Chowdhury Tara G. , Ríos Mariel B. , Chan Thomas E. , Cassataro Daniela S. , Barbarich‐Marsteller Nicole C. , Aoki Chiye
Published: June 2014

Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating and irrational fears of gaining weight. There is no accepted pharmacological treatment for AN, and AN has the highest mortality rate among psychiatric illnesses. Anorexia nervosa most commonly affects females during adolescence, suggesting an effect of sex and hormones on vulnerability to the disease. Activity‐based anorexia (ABA) is a rodent model of AN that shares symptoms with AN, including over‐exercise, elevation of stress hormones, and genetic links to anxiety traits. We previously reported that ABA in adolescent female rats results in increased apical dendritic branching in CA1 pyramidal cells of the ventral hippocampus at postnatal day 44 (P44). To examine the long‐term effects of adolescent ABA (P44) in female rats, we compared the apical branching in the ventral hippocampal CA1 after recovery from ABA (P51) and after a relapse of ABA (P55) with age‐matched controls. To examine the age‐dependence of the hippocampal plasticity, we examined the effect of ABA during adulthood (P67). We found that while ABA at P44 resulted in increased branching of ventral hippocampal pyramidal cells, relapse of ABA at P55 resulted in decreased branching. ABA induced during adulthood did not have an effect on dendritic branching, suggesting an age‐dependence of the vulnerability to structural plasticity. Cells from control animals were found to exhibit a dramatic increase in branching, more than doubling from P44 to P51, followed by pruning from P51 to P55. The proportion of mature spines on dendrites from the P44‐ABA animals is similar to that on dendrites from P55‐CON animals. These results suggest that the experience of ABA may cause precocious anatomical development of the ventral hippocampus. Importantly, we found that adolescence is a period of continued development of the hippocampus, and increased vulnerability to mental disorders during adolescence may be due to insults during this developmentally critical period. © 2014 Wiley Periodicals, Inc.
Multivariate pattern analysis of the human medial temporal lobe revealed representationally categorical cortex and representationally agnostic hippocampus
Authors: Huffman Derek J. , Stark Craig E.L.
Published: June 2014

Contemporary theories of the medial temporal lobe (MTL) suggest that there are functional differences between the MTL cortex and the hippocampus. High‐resolution functional magnetic resonance imaging and multivariate pattern analysis were utilized to study whether MTL subregions could classify categories of images, with the hypothesis that the hippocampus would be less representationally categorical than the MTL cortex. Results revealed significant classification accuracy for faces versus objects and faces versus scenes in MTL cortical regions—parahippocampal cortex (PHC) and perirhinal cortex (PRC)—with little evidence for category discrimination in the hippocampus. MTL cortical regions showed significantly greater classification accuracy than the hippocampus. The hippocampus showed significant classification accuracy for images compared to a nonmnemonic baseline task, suggesting that it responded to the images. Classification accuracy in a region of interest encompassing retrosplenial cortex (RSC) and the posterior cingulate cortex (PCC) posterior to RSC, showed a similar pattern of results to PHC, supporting the hypothesis that these regions are functionally related. The results suggest that PHC, PRC, and RSC/PCC are representationally categorical and the hippocampus is more representationally agnostic, which is concordant with the hypothesis of the role of the hippocampus in pattern separation. © 2014 Wiley Periodicals, Inc.
TR4 nuclear receptor promotes prostate cancer metastasis via upregulation of CCL2/CCR2 signaling
Authors: Ding Xianfan , Yang Dong‐Rong , Lee Soo Ok , Chen Ya‐Ling , Xia Liqun , Lin Shin‐Jen , Yu Shicheng , Niu Yuan‐Jie , Li Gonghui , Chang Chawnshang
Published: June 2014

Testicular nuclear receptor 4 (TR4) plays protective roles against oxidative stress and DNA damage and might contribute to aging. Our recent clinical tumor tissue staining results showed higher expression of TR4 in prostate cancer (PCa) patients with high Gleason scores compared to the tissues with the low Gleason scores. In vitro migration/invasion assays after manipulation of the TR4 expression in PCa cells showed that TR4 promoted PCa cells migration/invasion. Mechanism dissection found that the CCL2/CCR2 signal plays the key role in the mediation of TR4‐promoted PCa cells migration/invasion. Chromatin immunoprecipitation and Luciferase assays further confirmed TR4 modulation of CCL2 at the transcriptional level and addition of the CCR2 antagonist led to interruption of the TR4‐enhanced PCa cells migration/invasion. Finally, the orthotopic xenografted mice studies using the luciferase expressing CWR22Rv1 cells found that TR4 enhanced PCa metastasis and this increased metastasis was reversed when the CCR2 antagonist was injected into the mice. Together, these in vitro and in vivo results revealed a positive role of TR4 in PCa metastasis and demonstrated CCL2/CCR2 signaling as an important mediator in exerting TR4 action. This finding suggests that TR4 may represent a biomarker related to PCa metastasis and targeting the TR4‐CCL2/CCR2 axis may become a new therapeutic approach to battle PCa metastasis.
A melanin‐independent interaction between Mc1r and Met signaling pathways is required for HGF‐dependent melanoma
Authors: Wolnicka‐Glubisz Agnieszka , Strickland Faith M. , Wielgus Albert , Anver Miriam , Merlino Glenn , De Fabo Edward C. , Noonan Frances P.
Published: June 2014

Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP‐dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well‐described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV‐induced melanoma. C57BL/6‐Mc1r+/+‐HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra‐follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA‐induced and spontaneous melanomas are dependent on black eumelanin. We crossed these mice with yellow C57BL/6‐Mc1re/e animals which have a non‐functional Mc1r and produce predominantly yellow phaeomelanin. Yellow C57BL/6‐Mc1re/e‐HGF mice produced no melanoma in response to UVR or spontaneously even though the HGF transgene and its receptor Met were expressed. Total melanin was less than in C57BL/6‐Mc1r+/+‐HGF mice, hyperpigmentation was not observed and there were few extra‐follicular melanocytes. Thus, functional Mc1r was required for expression of the transgenic HGF phenotype. Heterozygous C57BL/6‐Mc1re/+‐HGF mice were black and hyperpigmented and, although extra‐follicular melanocytes and skin melanin content were similar to C57BL/6‐Mc1r+/+‐HGF animals, they developed UV‐induced and spontaneous melanomas with significantly less efficiency by all criteria. Thus, heterozygosity for Mc1r was sufficient to restore the transgenic HGF phenotype but insufficient to fully restore melanoma. We conclude that a previously unsuspected melanin‐independent interaction between Mc1r and Met signaling pathways is required for HGF‐dependent melanoma and postulate that this pathway is involved in human melanoma.
A prospective study of one‐carbon metabolism biomarkers and cancer of the head and neck and esophagus
Authors: Fanidi Anouar , Relton Caroline , Ueland Per Magne , Midttun Øivind , Vollset Stein Emil , Travis Ruth C. , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Bueno‐de‐Mesquita H B(as) , Ros Martine , Boeing Heiner , Tumino Rosario , Panico Salvatore , Palli Domenico , Sieri Sabina , Vineis Paolo , Sánchez María‐José , Huerta José María , Barricarte Gurrea Aurelio , Luján‐Barroso Leila , Quirós J Ramón , Tjønneland Anne , Halkjær Jytte , Boutron‐Ruault Marie‐Christine , Clavel‐Chapelon Françoise , Cadeau Claire , Weiderpass Elisabete , Johansson Mikael , Riboli Elio , Brennan Paul , Johansson Mattias
Published: June 2014

Experimental and epidemiological data suggest that factors of one‐carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre‐diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post‐diagnosis all‐cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4vs. Q1] being 2.13 (95% confidence interval [95% CI] 1.13–4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4vs. Q1 0.63, 95% CI 0.35–1.16, p for trend 0.02). Subgroup analyses by anatomical sub‐site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8 × 10−4), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck.
Elevated p53 promotes the processing of miR‐18a to decrease estrogen receptor‐α in female hepatocellular carcinoma
Authors: Li Chiao‐Ling , Yeh Kun‐Huei , Liu Wan‐Hsin , Chen Chi‐Ling , Chen Ding‐Shinn , Chen Pei‐Jer , Yeh Shiou‐Hwei
Published: June 2014

The estrogen pathway has long been implicated as a tumor protector in female hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC). Our previous study identified that estrogen receptor alpha (ERα) protein is downregulated in 60% of female HCC cases, via a miR‐18a elevation mediated suppression of ERα translation. This study aims to delineate the mechanism underlying the upregulation of miR‐18a in female HCC. The analysis of 77 female HCC specimens revealed that miR‐18a levels were associated with pre‐miR‐18a rather than pri‐miR‐18a levels, suggesting an enhanced processing of pri‐ to pre‐miR‐18a. Among a panel of factors involved in microRNA processing, p53 was identified as a novel regulator for miR‐18a maturation process. Knockdown of p53 by si‐RNA decreased the level of miR‐18a, whereas overexpression of either wild‐type or mutant p53 increased its level. The association between the elevation of miR‐18a and the accumulation of p53, mainly caused by somatic mutations, was confirmed in the clinical specimens of HBV‐related female HCC. By analyzing the association with clinicopathological features, activation of this p53/miR‐18a pathway mainly occurs in younger or noncirrhosis female HCC patients and associated with a trend of worse overall survival. Therefore, this study demonstrated a novel function of elevated/mutant p53 in regulating the amount of ERα protein through its promoting the biogenesis of miR‐18a, which could lead to decrease the tumor‐protective function of the estrogen pathway in female hepatocarcinogenesis.
Novel function of Oncostatin M as a potent tumour‐promoting agent in lung
Authors: Lauber Sean , Wong Steven , Cutz Jean‐Claude , Tanaka Minoru , Barra Nicole , Lhoták Šárka , Ashkar Ali , Richards Carl Douglas
Published: June 2014

Oncostatin M is a leukocyte product that has been reported to have anti‐proliferative effects directly on melanoma and other cancer cell lines in vitro. However, its function(s) in cancers in vivo appears complex and its roles in cancer growth in lungs are unknown. Here, we show that OSM promotes marked growth of tumour cells in mouse lungs. Local pulmonary administration of adenovirus vector expressing mouse OSM (AdOSM) induced >13‐fold increase in lung tumour burden of ectopically delivered B16‐F10 melanoma cells in C57BL/6 mice. AdOSM caused increases in tumour size (14 days post‐challenge), whereas control vector (Addel70) did not. AdOSM had no such action in C57BL/6 mice deficient in the OSM receptor beta chain (OSMRβ−/−), indicating that these effects required OSMRβ expression on non‐tumour cells in the recipient mice. AdOSM induced elevated levels of chemokines and inflammatory cells in the bronchoalveolar lavage (BAL) fluid, elevated arginase‐1 mRNA levels (60‐fold), and increased arginase‐1+immunostaining macrophage numbers in lungs. Adherent BAL cells collected from AdOSM‐treated mice expressed elevated arginase‐1 activity. In contrast to AdOSM‐induced effects, pulmonary over‐expression of IL‐1β (AdIL‐1β) induced neutrophil accumulation and iNOS mRNA, but did not modulate tumour burden. AdOSM also increased lung tumour load (>50‐fold) upon ectopic administration of Lewis lung carcinoma (LLC) cells in vivo. However, in vitro, neither recombinant OSM nor AdOSM infection stimulated B16‐F10 or LLC cell growth directly. We conclude that pulmonary over‐expression of OSM promotes tumour growth, and does so through altering the local lung environment with accumulation of M2 macrophages.
Peroxisome proliferator‐activated receptor γ upregulates galectin‐9 and predicts prognosis in intestinal‐type gastric cancer
Authors: Cho Soo‐Jeong , Kook Myeong‐Cherl , Ho Lee Jun , Shin Ji‐Young , Park JuRi , Bae Young‐Ki , Ju Choi Il , Won Ryu Keun , Kim Young‐Woo
Published: June 2014

The importance of PPARγ (peroxisome proliferator‐activated receptor γ) in gastric cancer (GC) is unclear. We investigated the role of PPARγ in GC cell lines and an animal model, and its prognostic significance of PPARγ in GC patients. We controlled PPARγ and galectin‐9 expression by using siRNAs and lentiviral constructs. Interaction between PPARγ and galectin‐9 was evaluated using luciferase and chromatin immunoprecipitation assays. PPARγ expression in GCs was determined by immunohistochemical staining of tissue microarrays and survival analysis was done. Overexpression of PPARγ was accompanied by increased galectin‐9. Enhanced PPARγ or galectin‐9 expression increased E‐cadherin expression; decreased expression of N‐cadherin, fibronectin, snail, twist and slug and reduced cell invasion and migration. PPARγ bound to the galectin‐9 promoter region. Galectin‐9 activity increased in PPARγ‐overexpressing cells but decreased in PPARγ siRNA‐treated cells. In a zebrafish xenograft model, the number of migrated cancer cells and number of fish with AGS cells in the tail vein were reduced in PPARγ‐overexpressing GC cells. PPARγ was expressed in 462 of the 688 patients (69.2%) with GC. In 306 patients with intestinal‐type GC, those with PPARγ‐positive tumors had lower overall and cancer‐specific mortalities than those with PPARγ‐negative tumors. PPARγ expression was an independent prognostic factor for overall and GC‐specific mortality in patients with intestinal‐type GC (adjusted hazard ratio, 0.42; 95% CI, 0.22–0.81). PPARγ inhibits cell invasion, migration and epithelial–mesenchymal transition through upregulation of galectin‐9 in vitro and in vivo.
Artemisinin and Curcumin inhibit Drosophila brain tumor, prolong life span, and restore locomotor activity
Authors: Das Sourajit Soumyaranjan , Nanda Gargi Gouranga , Alone Debasmita Pankaj
Published: June 2014

Deletion of tumor suppressor gene, lethal(2)giant larvae [l(2)gl], leads to brain tumor in Drosophila melanogaster at larval stage of development and severe brain dysplasia in mice. We have studied the effect of two potential antitumor drugs artemisinin and curcumin in the perspective of inhibiting l(2)gl brain tumor. Efficacies of these drugs are characterized morphologically by measuring brain sizes of untreated and treated larvae on the basis of tumor inhibition and anatomically by looking at the cellular patterning via antibody staining of the third instar Drosophila larval brains. Behavioral experiments were done in form of locomotion to correlate tumor inhibition with the revival of brain function and longevity assays to assess general health span. It was observed that both drugs show antitumor properties individually and in combination when larvae were treated with these drugs. We also found evidence for reactive oxygen species‐mediated action of these drugs. Both the drugs when treated individually or together show better median life span and locomotory response. Although the efficacies of various treatments varied, overall, the positive effects of artemisinin and curcumin demonstrate a potential applicability of these drugs against brain tumor in higher organisms. It also paves a way for a simpler model system for screening such natural products for antitumor property. © 2014 IUBMB Life, 66(7):496–506, 2014
Preventing HIV infection: Pre‐exposure and postexposure prophylaxis
Authors: Doblecki‐Lewis Susanne , Kolber Michael A.
Published: June 2014

Data supporting the use of pre‐exposure prophylaxis (PrEP) and nonoccupational postexposure prophylaxis (nPEP) in the prevention of HIV infection after a sexual encounter continue to grow. In this review, we describe some of the research driving the various recommendations for use of antiretrovirals in prevention. In addition, current research is described regarding the establishment of viral reservoirs that argues for rethinking the timing for nPEP treatment. We discuss the variables that impact on the choice of prevention antiretrovirals, including drug distribution, drug transporters, and potential impact of race and ethnicity on these variables. © 2014 IUBMB Life, 66(7):453–461, 2014
The effect of APH treatment on surface bonding and osseointegration of Ti‐6Al‐7Nb implants: An in vitro and in vivo study
Authors: Nguyen Thuy‐Duong Thi , Moon So‐Hee , Oh Tae‐Ju , Park Il‐Song , Lee Min‐Ho , Bae Tae‐Sung
Published: June 2014

This study investigated the effects of anodization‐cyclic precalcification‐heat (APH) treatment on the bonding ability of Ca‐P coating to the parent metal and osseointegration of Ti‐6Al‐7Nb implants. Eighteen Ti‐6Al‐7Nb discs, 9 untreated and 9 APH‐treated, were cultured with osteoblast cells in vitro, and the cellular differentiation ability was assayed at 1, 2, and 3 weeks. For in vivo testing, 28 Ti‐6Al‐7Nb implants (14 implants of each group) were inserted to rat tibias, and after each 4 and 6 weeks of implantation, bone bonding, and osseointegration were evaluated through removal torque and histological analysis. Osteoblast‐culturing showed twice as much of the alkaline phosphatase activity on the treated surface at 3 weeks than on the untreated surface (p < 0.05). The treated implants exhibited higher removal torque values than the untreated ones (15.5 vs. 1.8 Ncm at 4 weeks and 19.7 vs. 2.6 Ncm at 6 weeks, p < 0.05). Moreover, the excellent bonding quality of coats was confirmed by the existence of cohesive fractures on the surface of removed APH implants (field emission scanning electron microscopy and histological observation). Within the limits of this study, it can be concluded that the APH treatment significantly enhanced osseointegration of the Ti‐6Al‐7Nb implant, with the stable bonding between the coating and the implant surface. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 641–648, 2015.
Differences in Mathematical Performance, Creativity Potential, and Need for Cognitive Closure between Chinese and Australian Students
Authors: Ma Choi‐Chi Evelene , Rapee Ronald M.
Published: June 2014

Research has shown that Chinese students outperform students from several Western countries on mathematics performance while some evidence has suggested that Western students perform more strongly on tests of creativity. One potential mechanism for these differences may be a higher need for cognitive closure among Chinese students. The current research compared performance on tests of mathematics and creativity among 50 students of Chinese background and 49 Australian students of Anglo‐Saxon background. As predicted, Chinese students performed better on mathematics while Australian students performed better on the measure of creativity. Australian students also had a lower score on one subscale of the need for cognitive closure, preference for predictability. Across the sample, preference for predictability showed small but significant negative correlations with several measures of creativity and positive correlations with several measures of mathematics. These findings were interpreted with respect to characteristic educational practices in both nations.
Investigation of Psychometric Properties of the Test for Creative Thinking—Drawing Production: Evidence from Study in Latvia
Authors: Kālis Emīls , Roķe Līga , Krūmiņa Indra
Published: June 2014

The Test for Creative Thinking—Drawing Production (TCT‐DP) is designed as an effective drawing‐based instrument for measuring creative potential. Many studies report adaptation efforts in other cultures pointing out good psychometric properties of the instrument nonetheless revealing also some trouble spots. The present study includes adaptation of TCT‐DP in Latvia and investigation of psychometric properties of the instrument such as measurement invariance between forms, sequence effect, gender differences, and factor structure of criteria employing methodology of structural equation modeling. Two samples were involved in the study—9th‐grade students (n = 300) and 15‐year‐old 9th‐grade students (n = 200). Results indicate that trained judges are able to achieve high reliability in evaluation of TCT‐DP total score and all criteria if some criteria are divided into subcategories. It was also found that TCT‐DP has measurement invariance between both forms but has small effect sizes regarding gender differences and method sequence. Observed differences of TCT‐DP total scores between the Latvian sample and relevant samples from Germany and Hong Kong could be considered as trivial. The study also revealed that, following original instructions, some test criteria had strong interdependence and therefore strategies in the evaluation process reducing interdependencies between criteria should be considered in future studies on the structure of TCT‐DP.
Determination of organochlorine pesticides in snow water samples by low density solvent based dispersive liquid–liquid microextraction
Authors: Zhao Wenting , Li Jindong , Wu Tong , Wang Peng , Zhou Zhiqiang
Published: June 2014

A simple, rapid, efficient, and environmentally friendly pretreatment based on a low‐density solvent based dispersive liquid–liquid microextraction was developed for determining trace levels of 17 organochlorine pesticides in snow. The parameters affecting the extraction efficiency, such as the type and volume of the extraction and dispersive solvents, extraction time, and salt content, were optimized. The optimized conditions yielded a good performance, with enrichment factors ranging from 271 to 474 and recoveries ranging from 71.4 to 114.5% and relative standard deviations between 1.6 and 14.8%. The detection limits, calculated as three times the signal‐to‐noise ratio, ranged from 0.02 to 0.11 μg/L. The validated method was used to successfully analyze 17 analytes in snow water samples, overcoming the drawbacks of some existing low‐density solvent liquid microextraction methods, which require special devices, large volumes of organic solvents, or complicated operation procedures.
Evaluation and comparison of n‐alkyl chain and polar ligand bonded stationary phases for protein separation in reversed‐phase liquid chromatography
Authors: Ding Ling , Guo Zhimou , Xiao Yuansheng , Xue Xingya , Zhang Xiuli , Liang Xinmiao
Published: June 2014

Protein retention is very sensitive to the change of solvent composition in reversed‐phase liquid chromatography for so called “on–off” mechanism, leading to difficulty in mobile phase optimization. In this study, a novel 3‐chloropropyl trichlorosilane ligand bonded column was prepared for protein separation. The differences in retention characteristics between the 3‐chloropropyl trichlorosilane ligand bonded column and n‐alkyl chain modified (C2, C4, C8) stationary phases were elucidated by the retention equation . Retention parameters (a and c) of nine standard proteins with different molecular weights were calculated by using homemade software. Results showed that retention times of nine proteins were similar on four columns, but the 3‐chloropropyl trichlorosilane ligand bonded column obtained the lowest retention parameter values of larger proteins. It meant that their retention behavior affected by acetonitrile concentration would be different due to lower |c| values. More specifically, protein elution windows were broader, and retentions were less sensitive to the change of acetonitrile concentration on the 3‐chloropropyl trichlorosilane ligand bonded column than that on other columns. Meanwhile, the 3‐chloropropyl trichlorosilane ligand bonded column displayed distinctive selectivity for some proteins. Our results indicated that stationary phase with polar ligand provided potential solutions to the “on–off” problem and optimization in protein separation.
Extraction of aflatoxins from food samples using graphene‐based magnetic nanosorbents followed by high‐performance liquid chromatography: A simple solution to overcome the problems of immunoaffinity columns
Authors: Es'haghi Zarrin , Reza Beheshti Hamed , Feizy Javad
Published: June 2014

In this research, magnetic graphene nanoparticles were prepared and used as adsorbents for preconcentrating the aflatoxins in rice, wheat, and sesame samples. For this purpose, graphene was synthesized by Hummer's method. Magnetically modified graphene formed by the deposition of magnetite (Fe3O4) on graphene was used for the separation of aflatoxins B1, B2, G1, and G2 from the samples. The extractants were subsequently analyzed with high‐performance liquid chromatography and fluorescence detection. Parameters affecting the efficiency of the method were thoroughly investigated. The measurements were done under the optimized conditions. For aflatoxins B1, B2, G1, and G2, limits of detection were 0.025, 0.05, 0.05, and 0.075 ng/g and limits of quantification were 0.083, 0.16, 0.16, and 0.23 ng/g, respectively. Accuracy was examined by the determination of the relative recovery of the aflatoxins. The relative recovery of aflatoxins B1, B2, G1, and G2 were quite satisfactory (between 64.38 and 122.21% for food samples). Relative standard deviations for within laboratory repeatability (n = 6) were in the range from 1.3 to 3.2. The application of this sorbent for the separation and concentration of the mentioned aflatoxins from food samples was examined.
The prevalence of Parkinson's disease: A systematic review and meta‐analysis
Authors: Pringsheim Tamara , Jette Nathalie , Frolkis Alexandra , Steeves Thomas D.L.
Published: June 2014

Parkinson's Disease (PD) is a common neurodegenerative disorder. We sought to synthesize studies on the prevalence of PD to obtain an overall view of how the prevalence of this disease varies by age, by sex, and by geographic location. We searched MEDLINE and EMBASE for epidemiological studies of PD from 1985 to 2010. Data were analyzed by age group, geographic location, and sex. Geographic location was stratified by the following groups: 1) Asia, 2) Africa, 3) South America, and 4) Europe/North America/Australia. Meta‐regression was used to determine whether a significant difference was present between groups. Forty‐seven studies were included in the analysis. Meta‐analysis of the worldwide data showed a rising prevalence of PD with age (all per 100,000): 41 in 40 to 49 years; 107 in 50 to 59 years; 173 in 55 to 64 years; 428 in 60 to 69 years; 425 in 65 to 74 years; 1087 in 70 to 79 years; and 1903 in older than age 80. A significant difference was seen in prevalence by geographic location only for individuals 70 to 79 years old, with a prevalence of 1,601 in individuals from North America, Europe, and Australia, compared with 646 in individuals from Asia (P < 0.05). A significant difference in prevalence by sex was found only for individuals 50 to 59 years old, with a prevalence of 41 in females and 134 in males (P < 0.05). PD prevalence increases steadily with age. Some differences in prevalence by geographic location and sex can be detected. © 2014 International Parkinson and Movement Disorder Society
Suprathreshold odor intensity perception in early‐stage Parkinson's disease
Authors: Doty Richard L. , Beals Evan , Osman Allen , Dubroff Jacob , Chung Inna , Leon‐Sarmiento Fidias E. , Hurtig Howard , Ying Gui‐Shuang
Published: June 2014

Background

Whether Parkinson's disease (PD) influences suprathreshold changes in perceived odor intensity is unknown. In patients with Alzheimer's disease, patients with schizophrenia, and the elderly, such perception is reportedly normal. If generally true, this could reflect a core element of the olfactory system insulated to some degree from age‐ and disease‐related pathological conditions.

Methods

Odor intensity ratings for pentyl acetate were obtained from 29 early‐stage PD patients when on and off dopamine‐related medications (DRMs) and from 29 matched controls.

Results

The ratings were significantly attenuated at the higher odorant concentrations, with the degree of attenuation associated with overall olfactory dysfunction. Ratings were higher on the right than on the left side of the nose of both patients and controls. No associations with DRMs, Unified Parkinson's Disease Rating Scale (UPDRS) scores, or striatal dopamine transporter imaging were found.

Conclusions

Parkinson's disease (PD) influences suprathreshold estimates of perceived odor intensity, negating the notion that such perception might be spared in this disease. No association with dopaminergic processes was apparent. © 2014 International Parkinson and Movement Disorder Society
NMR molecular dynamics study of chromonic liquid crystals Edicol Sunset Yellow doped with salts
Authors: de Almeida Martins João P. , Chávez Fabián Vaca , Sebastião Pedro J.
Published: June 2014

We investigate the effect of monoatomic salts on the molecular dynamics in the nematic and isotropic phases formed by the chromonic liquid crystal Edicol Sunset Yellow. The study was carried out using proton nuclear magnetic resonance relaxometry. To analyse the effect of incorporation of additional sodium chloride or lithium chloride on the solutions’ molecular dynamics, the spin‐lattice relaxation time was measured for Larmor frequencies between 10kHz and 100MHz. In the nematic phase, the presence of additional sodium or lithium ions seems to contribute to an increase of the rotations/reorientations correlation times in comparison with the mixture without extra ions. The collective motions detected by proton NMR relaxometry are associated with collective fluctuations of molecules within the stacks in the nematic phase and with order parameter fluctuations in the isotropic phase. Copyright © 2014 John Wiley & Sons, Ltd.
NMR of bent‐core nematogens: a mini‐review
Authors: Figueirinhas João L. , Dong Ronald Y.
Published: June 2014

This review focuses on two of our studied bent‐core liquid crystals 2‐methyl‐3‐[4‐(4‐octylbenzoyloxy)‐benzylidene]‐amino‐benzoic acid 4‐(4‐dodecylphenylazo)‐phenyl ester A131, and a shape‐persistent fluorenone mesogen, F1a by means of temperature‐dependent 13C NMR spectra and deuterium NMR spectra, respectively. Orientational order parameters, molecular packing, and/or conformations in the nematic phases or nematic glass can be extracted from the observed NMR spectra. These will be discussed in terms of certain motional models. In particular, F1a has been found to form a biaxial nematic glass. The derived orientational order parameters would put the biaxial system of phase symmetry lower than orthorhombic. Copyright © 2014 John Wiley & Sons, Ltd.
Facile preparation of PLGA microspheres with diverse internal structures by modified double‐emulsion method for controlled release
Authors: Han Fengxuan , Zhou Fang , Yang Xiaoling , Zhao Jin , Zhao Yunhui , Yuan Xiaoyan
Published: June 2014

Poly(l‐lactide‐co‐glycolide) (PLGA) microspheres with diverse internal structures and different release behaviors were prepared via a modified double‐emulsion method by introduction of heparin or carboxymethyl chitosan in the inner aqueous phase and calcium chloride in the outer aqueous phase, respectively. The main factors affecting the microsphere morphology were systematically studied, including compositions in the inner aqueous phase, the oily phase, and the outer aqueous phase. The transmission electron microscope images demonstrated that the microspheres are featured with single core, hollow, and multicore structures when their sizes were less than 200 nm, in the range of 200–700 nm, and greater than 700 nm, respectively. In comparison with hollow PLGA microspheres, the PLGA microspheres with heparin and carboxymethyl chitosan in the inner aqueous phase also showed multicore and single core structures, respectively, and exhibited higher loading efficiencies and slower release rates by using bovine serum albumin as a model for bioactive substances. It was concluded that this study provided a facile method to prepare microspheres with single core, multicore, or hollow feature, and the tunability of the different internal structures and related release profiles enables these systems cater to specific requirements for potential applications in controlled biomolecule delivery for tissue regeneration. POLYM. ENG. SCI., 55:896–906, 2015. © 2014 Society of Plastics Engineers
Electrical transport and morphological studies of polyaniline nanostructures
Authors: Chutia P. , Kumar A.
Published: June 2014

Polyaniline nanostructures have been synthesized by self‐assembly method by varying the dopant to monomer molar ratio. High resolution transmission electron micrographs show how the dopant to monomer molar ratio influences on the morphology and structure. The temperature dependence of dc conductivity study shows semiconducting behavior. From dc conductivity study it has been observed that conductivity increases with increasing dopant concentration and maximum conductivity is attained at dopant to monomer molar ratio of 3:4. From the slope of the reduced activation energy versus temperature plot it is confirmed that the charge transport in polyaniline nanostructures is in insulating regime and dominated by variable range hopping mechanism. In particular, a crossover from 1D to 3D variable range hopping conduction is observed by changing the dopant to monomer molar ratio. With increasing the dopant concentration the 680 nm absorption peak shifted towards higher wavelength range. The red shifting of this peak indicates the increased extent of π‐conjugation length. The enhancement of characteristic band intensity at 1336 cm−1 in Micro‐Raman spectra indicates the increase of delocalization degree. Temperature profiles of the degradation processes have been mapped using thermogravimetry analyzer and it is observed three‐step weight losses for all the samples. POLYM. ENG. SCI., 55:995–1002, 2015. © 2014 Society of Plastics Engineers