Rejection Sensitivity and Social Outcomes of Young Adult Men with ADHD

ERIC Educational Resources Information Center

Canu, Will H.; Carlson, Caryn L.

2007-01-01

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) has been consistently linked to social maladjustment. This study investigated whether elevated rejection sensitivity (RS) could contribute to the relational problems that adults with ADHD encounter. Method: Undergraduate men in ADHD-Combined Type (ADHD-C; n = 31), ADHD-Primarily…

Examining Appearance-Based Rejection Sensitivity during Early Adolescence

ERIC Educational Resources Information Center

Bowker, Julie C.; Thomas, Katelyn K.; Spencer, Sarah V.; Park, Lora E.

2013-01-01

The present study of 150 adolescents ("M" age = 13.05 years) examined the associations between appearance-based rejection sensitivity (Appearance-RS) and psychological adjustment during early adolescence, and evaluated three types of other-gender peer experiences (other-gender friendship, peer acceptance, and romantic relationships) as…

Distinguishing institutional identification from academic goal pursuit: interactive effects of ethnic identification and race-based rejection sensitivity.

PubMed

Mendoza-Denton, Rodolfo; Pietrzak, Janina; Downey, Geraldine

2008-08-01

We examined the interactive effects of ethnic identification (EI) and race-based rejection sensitivity (RS-race) on institutional outcomes among African American college students. We distinguished between effects on institutional identification on the one hand and academic goal pursuit (e.g., staying in school, grade point average [GPA]) on the other. Supporting the utility of this distinction, we found that EI and RS-race interacted to predict these outcomes differently. Higher EI in combination with higher RS-race predicted reduced identification with the institution (Studies 1, 2, and 3a). This combination, however, did not lead to decreases in GPA over time. Moreover, EI was positively related to intentions to stay in school as well as to GPA increases among those lower in RS-race (Studies 1 and 3b). Implications for understanding identity negotiation vis-à-vis performance in institutional settings are discussed. (c) 2008 APA, all rights reserved

Stress and coping in interracial contexts: The influence of race-based rejection sensitivity and cross-group friendship in daily experiences of health

PubMed Central

Page-Gould, Elizabeth; Mendoza-Denton, Rodolfo; Mendes, Wendy Berry

2014-01-01

We examined the interplay of psychosocial risk and protective factors in daily experiences of health. In Study 1, the tendency to anxiously expect rejection from racial outgroup members, termed race-based rejection sensitivity (RS-race), was cross-sectionally related to greater stress-symptoms among Black adults who reported fewer cross-race friends but not among participants who had more cross-race friends. In Study 2, we experimentally manipulated the development of a same- versus cross-race friendship among Latino/a-White dyads prior to collecting daily experiences of stress-symptoms using a diary methodology. While RS-race predicted more psychosomatic symptoms in the same-race friendship condition, RS-race was unrelated to symptomatology among participants who made a cross-race friend. These findings suggest that experiences of intergroup stress can spill over into everyday life in the absence of positive contact, but cross-race friendships may be a resource that mitigates the expression of interracial stress. PMID:25045176

Rejection Sensitivity and Executive Control: Joint predictors of Borderline Personality features

PubMed Central

Ayduk, Özlem; Zayas, Vivian; Downey, Geraldine; Cole, Amy Blum; Shoda, Yuichi; Mischel, Walter

2008-01-01

Two studies tested the hypothesis that rejection sensitivity (RS) and executive control (EC) jointly predict borderline personality (BP) features. We expected high RS to be related to increased vulnerability for BP features specifically in people who also had difficulties in executive control (EC). Study 1 tested this hypothesis using a sample of college students (N = 379) whereas Study 2 (N = 104) was conducted using a community sample of adults. Both studies operationalized EC by a self-report measure. For a subsample in Study 2 (N = 80), ability to delay gratification at age 4 was also used as an early behavioral precursor of EC in adulthood. In both studies, high RS was associated with increased BP features among people low in self-reported EC. Among those high in self-reported EC, the relationship between RS and BP features was attenuated. Study 2 found parallel findings using preschool delay ability as a behavioral index of EC. These findings suggest that EC may protect high RS people against BP features. PMID:18496604

Race-based rejection sensitivity partially accounts for the relationship between racial discrimination and distressing attenuated positive psychotic symptoms.

PubMed

Anglin, Deidre M; Greenspoon, Michelle; Lighty, Quenesha; Ellman, Lauren M

2016-10-01

Self-reported experiences of racial discrimination have been associated with a continuum of psychotic experiences in racial and ethnic minority populations; however, the underlying mechanisms of this relationship are not yet clear. Race-based rejection sensitivity (RS-race) has been associated with thought intrusions about being the target of racial discrimination; therefore, the present study aimed to determine whether RS-race accounts for the relationship between racial discrimination and psychotic-like experiences in racial and ethnic minority populations. A sample of 644 young adults from a US urban, predominantly immigrant, and racial and ethnic minority population was administered a self-report inventory of psychosis risk (i.e. Prodromal Questionnaire (PQ) ), providing a dimensional assessment of the total number of attenuated positive psychotic symptoms experienced as distressing (APPS-distress). Participants also completed the Experiences of Discrimination Questionnaire and the Rejection Sensitivity Questionnaire-Race. Hierarchical linear regression analyses revealed that RS-race and racial discrimination were both significantly related to higher levels of APPS-distress. Bootstrapping analyses of indirect effects indicated that RS-race partially accounted for the relationship between racial discrimination and APPS-distress. Although the cross-sectional nature of the data limits conclusions about causal inference, our findings do suggest that racial discrimination and RS-race may both be important for understanding risk for distress in the psychotic spectrum among racial and ethnic minority young adults. Some individuals who report racial discrimination may be more vulnerable to APPS-distress in part because they are anxiously anticipating being racially slighted, and this should be explored further in prospective clinical high-risk studies. © 2014 Wiley Publishing Asia Pty Ltd.

Correlation of IMPDH1 gene polymorphisms with subclinical acute rejection and mycophenolic acid exposure parameters on day 28 after renal transplantation.

PubMed

Kagaya, Hideaki; Miura, Masatomo; Saito, Mitsuru; Habuchi, Tomonori; Satoh, Shigeru

2010-08-01

The risk of acute rejection in patients with higher exposure to mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), might be due to inosine 5'-monophosphate dehydrogenase (IMPDH) polymorphisms. The correlations with subclinical acute rejection, IMPDH1 polymorphisms and MPA exposure on day 28 post-transplantation were investigated in 82 Japanese recipients. Renal transplant recipients were given combination immunosuppressive therapy consisting of tacrolimus and 1.0, 1.5 or 2.0 g/day of MMF in equally divided doses every 12 hr at designated times. There were no significant differences in the incidence of subclinical acute rejection between IMPDH1 rs2278293 or rs2278294 polymorphisms (p = 0.243 and 0.735, respectively). However, in the high MPA night-time exposure range (AUC > 60 microg x h/ml and C(0 )> or = 1.9 microg/ml), there was a significant difference in the incidence of subclinical acute rejection between IMPDH1 rs2278293 A/A, A/G and G/G genotypes (each p = 0.019), but not the IMPDH1 rs2278294 genotype. In the higher daytime MPA exposure range, patients with the IMPDH1 rs2278293 G/G genotype also tended to develop subclinical acute rejection. In patients with the IMPDH rs2278293 A/A genotype, the risk of subclinical acute rejection episode tends to be low and the administration of MMF was effective. The risk of subclinical acute rejection for recipients who cannot adapt in therapeutic drug monitoring (TDM) of MPA seems to be influenced by IMPDH1 rs2278293 polymorphism. The prospective analysis of IMPDH1 rs2278293 polymorphism as well as monitoring of MPA plasma concentration after transplantation might help to improve MMF therapy.

Lack of Association between Interleukin-10 Gene Polymorphisms and Graft Rejection Risk in Kidney Transplantation Recipients: A Meta-Analysis

PubMed Central

Xiong, Jiachuan; Wang, Yiqin; Zhang, Ying; Nie, Ling; Wang, Daihong; Huang, Yunjian; Feng, Bing; Zhang, Jingbo; Zhao, Jinghong

2015-01-01

Background Interleukin-10 (IL-10) is an important immunomodulatory cytokine. Several studies focused the association between IL-10 promoter gene polymorphisms and graft rejection risk in kidney transplantation recipients. However, the results of these studies remain inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations. Methods The PubMed, Embase, and Ovid Medline databases were searched. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity. Results A total of 16 studies including 595 rejection patients and 1239 stable graft patients were included in order to study the IL-10 -1082 (rs1800896 G/A), -819 (rs1800871 C/T), -592 (rs1800872 C/A) and IL-10 (-1082,-819,-592) polymorphisms. The -1082 G/A polymorphism was not associated with an increased graft rejection risk (OR = 1.03; 95%CI, 0.85–1.25, P = 0.74 for GA+AA vs. GG model). Moreover, all of the -819 C/T (OR = 1.06, 95%CI, 0.79–1.42, P = 0.70 for TA+TT vs. CC model), -592 C/A (OR = 1.10, 95% CI, 0.85–1.42, P = 0.47 for AC+AA vs. CC model) and IL-10 (-1082,-819,-592) polymorphisms (OR = 1.00, 95%CI, 0.79–1.27, P = 0.98 for I+L vs. H model) did not increase the graft rejection risk. In addition, we also performed subgroup analysis by ethnic group (mainly in Europeans or Asians) and rejection type (acute or chronic). There was also lack of evidence of a significant association between the IL-10 gene polymorphism and graft rejection risk. The present meta-analysis indicated that the IL-10 gene polymorphism was not associated with graft rejection risk in kidney transplantation recipients. Conclusion This meta-analysis found evidence that the IL-10 polymorphism does not increase the risk of graft rejection in kidney transplantation recipients. Further chronic rejection and other ethnic population studies are needed to confirm our results. PMID:26035439

Enhanced B Cell Alloantigen Presentation and Its Epigenetic Dysregulation in Liver Transplant Rejection.

PubMed

Ningappa, M; Ashokkumar, C; Higgs, B W; Sun, Q; Jaffe, R; Mazariegos, G; Li, D; Weeks, D E; Subramaniam, S; Ferrell, R; Hakonarson, H; Sindhi, R

2016-02-01

T cell suppression prevents acute cellular rejection but causes life-threatening infections and malignancies. Previously, liver transplant (LTx) rejection in children was associated with the single-nucleotide polymorphism (SNP) rs9296068 upstream of the HLA-DOA gene. HLA-DOA inhibits B cell presentation of antigen, a potentially novel antirejection drug target. Using archived samples from 122 white pediatric LTx patients (including 77 described previously), we confirmed the association between rs9296068 and LTx rejection (p = 0.001, odds ratio [OR] 2.55). Next-generation sequencing revealed that the putative transcription factor (CCCTC binding factor [CTCF]) binding SNP locus rs2395304, in linkage disequilibrium with rs9296068 (D' 0.578, r(2) = 0.4), is also associated with LTx rejection (p = 0.008, OR 2.34). Furthermore, LTx rejection is associated with enhanced B cell presentation of donor antigen relative to HLA-nonidentical antigen in a novel cell-based assay and with a downregulated HLA-DOA gene in a subset of these children. In lymphoblastoid B (Raji) cells, rs2395304 coimmunoprecipitates with CTCF, and CTCF knockdown with morpholino antisense oligonucleotides enhances alloantigen presentation and downregulates the HLA-DOA gene, reproducing observations made with HLA-DOA knockdown and clinical rejection. Alloantigen presentation is suppressed by inhibitors of methylation and histone deacetylation, reproducing observations made during resolution of rejection. Enhanced donor antigen presentation by B cells and its epigenetic dysregulation via the HLA-DOA gene represent novel opportunities for surveillance and treatment of transplant rejection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Unstable identity compatibility: how gender rejection sensitivity undermines the success of women in science, technology, engineering, and mathematics fields.

PubMed

Ahlqvist, Sheana; London, Bonita; Rosenthal, Lisa

2013-09-01

Although the perceived compatibility between one's gender and science, technology, engineering, and mathematics (STEM) identities (gender-STEM compatibility) has been linked to women's success in STEM fields, no work to date has examined how the stability of identity over time contributes to subjective and objective STEM success. In the present study, 146 undergraduate female STEM majors rated their gender-STEM compatibility weekly during their freshman spring semester. STEM women higher in gender rejection sensitivity, or gender RS, a social-cognitive measure assessing the tendency to perceive social-identity threat, experienced larger fluctuations in gender-STEM compatibility across their second semester of college. Fluctuations in compatibility predicted impaired outcomes the following school year, including lower STEM engagement and lower academic performance in STEM (but not non-STEM) classes, and significantly mediated the relationship between gender RS and STEM engagement and achievement in the 2nd year of college. The week-to-week changes in gender-STEM compatibility occurred in response to negative academic (but not social) experiences.

Counter-regulation of rejection activity against human liver grafts by donor PD-L1 and recipient PD-1 interaction.

PubMed

Shi, Xiao-Lei; Mancham, Shanta; Hansen, Bettina E; de Knegt, Robert J; de Jonge, Jeroen; van der Laan, Luc J W; Rivadeneira, Fernando; Metselaar, Herold J; Kwekkeboom, Jaap

2016-06-01

Co-inhibitory receptor-ligand interactions fine-tune immune responses by negatively regulating T cell functions. Our aim is to examine the involvement of co-inhibitory receptor-ligand pair PD-1/PD-L1 in regulating rejection after liver transplantation (LT) in humans. PD-L1/PD-1 expression in liver allograft was determined by immunohistochemistry or flow cytometry, and the effect of blockade was studied using graft-infiltrating T cells ex vivo. Five single nucleotide polymorphisms within PD-1 and PD-L1 genes were genotyped in 528 LT recipients and 410 donors, and associations with both early (⩽6months) and late (>6months) acute rejection were analyzed using Cox proportional-hazards regression model. The effect of PD-L1 rs4143815 on PD-L1 expression was analyzed using donor hepatic leukocytes. PD-L1 was expressed by hepatocytes, cholangiocytes and along the sinusoids in post-transplant liver allografts, and PD-1 was abundantly expressed on allograft-infiltrating T cells. PD-L1 blockade enhanced allogeneic proliferative responses of graft-infiltrating T cells. In the genetic association analysis, donor PD-L1 rs4143815 (CC/CG vs. GG; HR=0.230; p=0.002) and recipient PD-1 rs11568821 (AA/AG vs. GG; HR=3.739; p=0.004) were associated with acute rejection late after LT in multivariate analysis. Recipients carrying the PD-1 rs11568821 A allele who were transplanted with liver grafts of PD-L1 rs4143815 GG homozygous donors showed the highest risk for late acute rejection. PD-L1 rs4143815 is associated with differential PD-L1 expression on donor hepatic dendritic cells upon IFN-γ stimulation. Our data suggest that interplay between donor PD-L1 and recipient PD-1 counter-regulates rejection activity against liver grafts in humans. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Individual differences in the impact of vicarious racism: African American students react to the George Zimmerman trial.

PubMed

Mason, Tyler B; Maduro, Ralitsa S; Derlega, Valerian J; Hacker, Desi S; Winstead, Barbara A; Haywood, Jacqueline E

2017-04-01

This research focused on how race-based rejection sensitivity (RS-Race) and components of racial identity intensify negative psychological reactions to an incident of vicarious racism. We examined how these individual difference variables directly and/or indirectly predicted African American students' reactions to the trial of George Zimmerman in the killing of the African American teenager, Trayvon Martin. In Study 1, 471 African American students completed measures of RS-Race, thought intrusions about the Zimmerman trial, and outcome variables (negative affect about the Zimmerman trial and forgiveness for Mr. Zimmerman). In Study 2, 304 African American students completed measures of racial identity (centrality, private regard, and public regard), thought intrusions about the Zimmerman trial, negative affect, and forgiveness. In Study 1, higher RS-Race was either directly and/or indirectly (via thought intrusions) related to more negative affect and lower forgiveness. In Study 2, high racial centrality and low public regard either directly and/or indirectly (via thought intrusions) predicted more negative affect and lower forgiveness. RS-Race and specific components of racial identity are likely to sensitize African Americans to incidents of racism that happen to other African Americans, leading to negative psychological reactions when these events occur. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT.

PubMed

Piras, Ignazio Stefano; Angius, Andrea; Andreani, Marco; Testi, Manuela; Lucarelli, Guido; Floris, Matteo; Marktel, Sarah; Ciceri, Fabio; La Nasa, Giorgio; Fleischhauer, Katharina; Roncarolo, Maria Grazia; Bulfone, Alessandro; Gregori, Silvia; Bacchetta, Rosa

2014-11-01

The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants-other than HLA class I and II-associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other (R(2)=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P<0.00001 for BAT2 SNP rs11538264, and P<0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs 2.6%, nominal P=1.15 × 10(-8); and adjusted P=0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT.

BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related stem cell transplantation

PubMed Central

Piras, Ignazio Stefano; Angius, Andrea; Andreani, Marco; Testi, Manuela; Lucarelli, Guido; Floris, Matteo; Marktel, Sarah; Ciceri, Fabio; La Nasa, Giorgio; Fleischhauer, Katharina; Roncarolo, Maria Grazia; Bulfone, Alessandro

2014-01-01

The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We applied a whole genome analysis to investigate genetic variants - other than HLA class I and II - associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single nucleotide polymorphisms in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong Linkage Disequilibrium between each other (R2=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P < 0.00001 for BAT2 SNP rs11538264, and P < 0.0001 for BAT3 SNP rs10484558). Whereas, the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs. 2.6%, nominal P = 1.15×10−8; and adjusted P = 0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT. PMID:25111513

Elucidating the relation between childhood emotional abuse and depressive symptoms in adulthood: The mediating role of maladaptive interpersonal processes

PubMed Central

Massing-Schaffer, Maya; Liu, Richard T.; Kraines, Morganne A.; Choi, Jimmy Y.; Alloy, Lauren B.

2015-01-01

Objective The purpose of this study is to assess the potential unique and relative mediating effects of three interpersonal risk factors (i.e., excessive reassurance-seeking [ERS], negative feedback seeking [NFS], and rejection sensitivity [RS]) in the relationship between childhood emotional abuse (CEA) and depressive symptoms. Method One hundred eighty-five undergraduates were followed over a four-month interval. Participants completed assessments of childhood abuse history, ERS, NFS, and RS, and depressive symptoms at baseline, as well as depressive symptoms at four-month followup. Results Findings from single-mediator analyses indicated that RS and NFS, but not ERS, mediated the relationship between CEA and prospective depressive symptoms, after accounting for childhood sexual and physical abuse, as well as baseline depressive symptoms. In our multi-mediator model, only RS remained a significant mediator of the relationship between CEA and prospective depressive symptoms. Conclusions The current study provides preliminary evidence that negative behavioral styles may function as a mechanism linking prior experiences of CEA to subsequent depressive symptoms. Clinical implications of these findings suggest that targeting maladaptive behavioral tendencies, particularly RS, may be an effective adjunct in behavioral modification treatments of CEA victims at risk for depression. PMID:26246650

Is love of nature in the US becoming love of electronic media? 16-year downtrend in national park visits explained by watching movies, playing video games, internet use, and oil prices.

PubMed

Pergams, Oliver R W; Zaradic, Patricia A

2006-09-01

After 50 years of steady increase, per capita visits to US national parks have declined since 1988. This decline, coincident with the rise in electronic entertainment media, may represent a shift in recreation choices with broader implications for the value placed on biodiversity conservation and environmentally responsible behavior. We compared the decline in per capita visits with a set of indicators representing alternate recreation choices and constraints. The Spearman correlation analyses found this decline in NPV to be significantly negatively correlated with several electronic entertainment indicators: hours of television, (rs=-0.743, P<0.001), video games (rs=-0.773, P<0.001), home movies (rs=-0.788, P<0.001), theatre attendance (rs=-0.587, P<0.025) and internet use (rs=-0.783, P<0.001). There were also significant negative correlations with oil prices (rs=-0.547, P<0.025), foreign travel (rs=-0.452, P<0.05), and Appalachian Trail hikers (rs=-0.785, P<0.001). Income was significantly positively correlated with foreign travel (rs=0.621, P<0.005) but negatively correlated with national park visits (rs=-0.697, P<0.005). There was no significant correlation of mean number of vacation days, indicating available vacation time is probably not a factor. Federal funding actually increased during this period, and so was rejected as a probable factor. Park capacity was rejected as limiting since both total overnight stays and visits at the seven most popular parks rose well into the mid-1990s. Aging of baby boomers was also rejected as they are only now reaching retirement age, and thus during the period of visitation decline were still of prime family vacation age. Multiple linear regression of four of the entertainment media variables as well as oil prices explains 97.5% of this recent decline (r=0.975, multiple r2=0.950, adjusted multiple r2=0.925, SE=0.015, F=37.800, P<0.0001). We may be seeing evidence of a fundamental shift away from people's appreciation of nature (biophilia, Wilson 1984) to 'videophilia,' which we here define as "the new human tendency to focus on sedentary activities involving electronic media." Such a shift would not bode well for the future of biodiversity conservation.

Long-Term Associations of Justice Sensitivity, Rejection Sensitivity, and Depressive Symptoms in Children and Adolescents

PubMed Central

Bondü, Rebecca; Sahyazici-Knaak, Fidan; Esser, Günter

2017-01-01

Depressive symptoms have been related to anxious rejection sensitivity, but little is known about relations with angry rejection sensitivity and justice sensitivity. We measured rejection sensitivity, justice sensitivity, and depressive symptoms in 1,665 9-to-21-year olds at two points of measurement. Participants with high T1 levels of depressive symptoms reported higher anxious and angry rejection sensitivity and higher justice sensitivity than controls at T1 and T2. T1 rejection, but not justice sensitivity predicted T2 depressive symptoms; high victim justice sensitivity, however, added to the stabilization of depressive symptoms. T1 depressive symptoms positively predicted T2 anxious and angry rejection and victim justice sensitivity. Hence, sensitivity toward negative social cues may be cause and consequence of depressive symptoms and requires consideration in cognitive-behavioral treatment of depression. PMID:28955257

Rejection Sensitivity, Jealousy, and the Relationship to Interpersonal Aggression.

PubMed

Murphy, Anna M; Russell, Gemma

2018-07-01

The development and maintenance of interpersonal relationships lead individuals to risk rejection in the pursuit of acceptance. Some individuals are predisposed to experience a hypersensitivity to rejection that is hypothesized to be related to jealous and aggressive reactions within interpersonal relationships. The current study used convenience sampling to recruit 247 young adults to evaluate the relationship between rejection sensitivity, jealousy, and aggression. A mediation model was used to test three hypotheses: Higher scores of rejection sensitivity would be positively correlated to higher scores of aggression (Hypothesis 1); higher scores of rejection sensitivity would be positively correlated to higher scores of jealousy (Hypothesis 2); jealousy would mediate the relationship between rejection sensitivity and aggression (Hypothesis 3). Study results suggest a tendency for individuals with high rejection sensitivity to experience higher levels of jealousy, and subsequently have a greater propensity for aggression, than individuals with low rejection sensitivity. Future research that substantiates a link between hypersensitivity to rejection, jealousy, and aggression may provide an avenue for prevention, education, or intervention in reducing aggression within interpersonal relationships.

Rejection sensitivity prospectively predicts increased rumination.

PubMed

Pearson, Katherine A; Watkins, Edward R; Mullan, Eugene G

2011-10-01

Converging research findings indicate that rumination is correlated with a specific maladaptive interpersonal style encapsulating submissive (overly-accommodating, non-assertive and self-sacrificing) behaviours, and an attachment orientation characterised by rejection sensitivity. This study examined the prospective longitudinal relationship between rumination, the submissive interpersonal style, and rejection sensitivity by comparing two alternative hypotheses: (a) the submissive interpersonal style and rejection sensitivity prospectively predict increased rumination; (b) rumination prospectively predicts the submissive interpersonal style and rejection sensitivity. Currently depressed (n = 22), previously depressed (n = 42) and never depressed (n = 28) individuals completed self-report measures assessing depressive rumination and key psychosocial measures of interpersonal style and behaviours, at baseline and again six months later. Baseline rejection sensitivity prospectively predicted increased rumination six months later, after statistically controlling for baseline rumination, gender and depression. Baseline rumination did not predict the submissive interpersonal style or rejection sensitivity. The results provide a first step towards delineating a potential casual relationship between rejection sensitivity and rumination, and suggest the potential value of clinical assessment and intervention for both rejection sensitivity and rumination in individuals who present with either difficulty. Copyright © 2011 Elsevier Ltd. All rights reserved.

Interactions Between Rejection Sensitivity and Supportive Relationships in the Prediction of Adolescents’ Internalizing Difficulties

PubMed Central

Bowker, Julie C.; Rubin, Kenneth H.; Laursen, Brett; Duchene, Melissa S.

2013-01-01

Rejection sensitivity, the tendency to anxiously or angrily expect rejection, is associated with internalizing difficulties during childhood and adolescence. The primary goal of the present study was to examine whether supportive parent–child relationships and friendships moderate associations that link angry and anxious rejection sensitivity to depression and social anxiety during middle adolescence in an ethnically diverse sample of 277 youth (M age = 14.30 years; 46.93% male). Analyses revealed that angry rejection sensitivity was related to depressive symptoms, but only for adolescents reporting low support from parents and friends. Friend support moderated the association between (1) angry rejection sensitivity and social anxiety, and (2) anxious rejection sensitivity and depressive symptoms. For adolescents reporting low support from friends, support from parents was positively related to social anxiety. Findings highlight the importance of considering relationships in studies of rejection sensitivity and adjustment during adolescence. PMID:20213482

The Mediating Roles of Rejection Sensitivity and Proximal Stress in the Association Between Discrimination and Internalizing Symptoms Among Sexual Minority Women.

PubMed

Dyar, Christina; Feinstein, Brian A; Eaton, Nicholas R; London, Bonita

2018-01-01

The negative impact of discrimination on mental health among lesbian, gay, and bisexual populations has been well documented. However, the possible mediating roles of sexual orientation rejection sensitivity and rejection-based proximal stress in the association between discrimination and internalizing symptoms remain unclear. Rejection-based proximal stress is a subset of proximal stressors that are theorized to arise from concerns about and expectations of sexual orientation-based rejection and discrimination. Drawing on minority stress theory, we tested potential mediating effects using indirect effects structural equation modeling in a sample of 300 sexual minority women. Results indicated that the indirect effect of discrimination on internalizing symptoms (a latent variable indicated by depression and anxiety symptoms) through sexual orientation rejection sensitivity and rejection-based proximal stress (a latent variable indicated by preoccupation with stigma, concealment motivation, and difficulty developing a positive sexual identity) was significant. Additionally, the indirect effects of discrimination on rejection-based proximal stress through sexual orientation rejection sensitivity and of sexual orientation rejection sensitivity on internalizing symptoms through rejection-based proximal stress were also significant. These findings indicate that sexual orientation rejection sensitivity plays an important role in contributing to rejection-based proximal stress and internalizing symptoms among sexual minority women.

The relations between secrecy, rejection sensitivity and autonomy-connectedness.

PubMed

Wismeijer, Andreas A J; Van Assen, Marcel A L M; Bekker, Marrie H J

2014-01-01

The aim of this study was to examine the effects of two attachment-related variables on secrecy: rejection sensitivity and autonomy-connectedness. We hypothesized that rejection sensitivity is positively associated with secrecy, and autonomy-connectedness negatively with rejection sensitivity and secrecy. These hypotheses were generally corroborated in a sample of 303 university students. Moreover, we found that autonomy-connectedness at least partly explained the association between rejection sensitivity and secrecy. Self-awareness was negatively related to secrecy, suggesting that being aware of what one needs and thinks and being able to realize one's needs in social interactions reduce the tendency to keep secrets. In addition, interesting gender effects were found suggesting that men have a higher tendency to have secrets than women after controlling for the effects of autonomy-connectedness and rejection sensitivity. Our findings deepen the insight into possible reasons behind established associations between rejection sensitivity and secrecy, and may have clinical implications.

Interactions between Rejection Sensitivity and Supportive Relationships in the Prediction of Adolescents' Internalizing Difficulties

ERIC Educational Resources Information Center

McDonald, Kristina L.; Bowker, Julie C.; Rubin, Kenneth H.; Laursen, Brett; Duchene, Melissa S.

2010-01-01

Rejection sensitivity, the tendency to anxiously or angrily expect rejection, is associated with internalizing difficulties during childhood and adolescence. The primary goal of the present study was to examine whether supportive parent-child relationships and friendships moderate associations that link angry and anxious rejection sensitivity to…

Extension of the Rejection Sensitivity Construct to the Interpersonal Functioning of Gay Men

ERIC Educational Resources Information Center

Pachankis, John E.; Goldfried, Marvin R.; Ramrattan, Melissa E.

2008-01-01

On the basis of recent evidence suggesting that gay men are particularly likely to fear interpersonal rejection, the authors set out to extend the "rejection sensitivity" construct to the mental health concerns of gay men. After establishing a reliable and valid measure of the gay-related rejection sensitivity construct, the authors use this to…

Free to be me: The relationship between the true self, rejection sensitivity, and use of online dating sites.

PubMed

Hance, Margaret A; Blackhart, Ginette; Dew, Megan

2018-01-01

Prior research (Blackhart et al., 2014) found that rejection-sensitive individuals are more likely to use online dating sites. The purpose of the current research was to explain the relationship between rejection sensitivity and online dating site usage. Study 1 examined whether true self mediated the relation between rejection sensitivity and online dating. Study 2 sought to replicate the findings of Study 1 and to examine whether self-disclosure moderated the relationship between true self and online dating in the mediation model. Results replicated those found by Blackhart et al. and also found that true self mediated the relationship between rejection sensitivity and online dating site usage. These findings suggest that rejection-sensitive individuals feel they can more easily represent their "true" selves in online environments, such as online dating sites, which partially explains why they are more likely to engage in online dating.

The roles of trauma exposure, rejection sensitivity, and callous-unemotional traits in the aggressive behavior of justice-involved youth: A moderated mediation model.

PubMed

Mozley, Michaela M; Modrowski, Crosby A; Kerig, Patricia K

2018-05-01

Research has demonstrated an association between childhood trauma exposure and adolescent aggression. This association may be explained by rejection sensitivity, defined as anger, or anxiety in the anticipation of rejection, which can be a consequence of trauma exposure. Callous-unemotional (CU) traits also are associated with trauma exposure and aggressive behavior; however, research has not yet investigated the interactive roles that rejection sensitivity and CU traits play in the relation between trauma exposure and aggression. Therefore, this study sought to investigate the role of rejection sensitivity in the association between trauma exposure and aggression, and whether this indirect effect was moderated by CU traits. Participants included 380 detained youth (98 girls, 282 boys) who completed self-report measures of trauma exposure, angry, and anxious rejection sensitivity, CU traits, and aggression. Results of moderated mediation demonstrated that the relation between trauma exposure and aggression exhibited an indirect effect through angry rejection sensitivity, but only at moderate or high levels of CU traits. This pattern was not found for anxious rejection sensitivity. Results suggest that interventions aimed to decrease aggressive behavior in traumatized adolescents may benefit from considering how youth respond to rejection, as well as whether youth endorse CU traits, as this may help to limit further involvement in the juvenile justice system after release. © 2018 Wiley Periodicals, Inc.

Women recovering from social rejection: The effect of the person and the situation on a hormonal mechanism of affiliation.

PubMed

Duffy, Korrina A; Harris, Lasana T; Chartrand, Tanya L; Stanton, Steven J

2017-02-01

Rejection can motivate either affiliation or withdrawal. In order to study how personality and situational variables influence whether women will be motivated to affiliate versus withdraw, we manipulate social feedback (rejection vs. acceptance) and opportunity for face-to-face interaction (blocked vs. face-to-face) and measure the individual difference variables rejection sensitivity and social anxiety. We test how these variables affect endogenous progesterone and cortisol concentrations, which are presumed to signal motivational responses to rejection. We find that three-way interactions involving social feedback, opportunity for face-to-face interactions, and either social anxiety or rejection sensitivity significantly predict progesterone change, but not cortisol change. Both interactions are driven by sharp progesterone decreases for women high in social anxiety/rejection sensitivity who have been rejected and who have no opportunity to reaffiliate in a face-to-face interaction. This progesterone change may be a physiological marker of motivation for social avoidance following rejection for women who cannot reaffiliate and who are particularly socially anxious or sensitive to rejection. Published by Elsevier Ltd.

Audience Activity and Media Use.

ERIC Educational Resources Information Center

Rubin, Alan M.

1993-01-01

Explores a view of audience behavior that lies between the extremes of a passive audience expected to be influenced by communication messages and an active audience expected to make rational decisions about what media content to accept and reject. (RS)

Association of vitamin D binding protein polymorphism with long-term kidney allograft survival in Hispanic kidney transplant recipients.

PubMed

Vu, Don; Sakharkar, Prashant; Tellez-Corrales, Eglis; Shah, Tariq; Hutchinson, Ian; Min, David I

2013-02-01

Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP G>T polymorphism (rs4588) and two haplotypes (GTCG and ACCA) of VDR appear to be associated with renal allograft outcomes among Hispanic allograft recipients.

Rejection Sensitivity Mediates the Relationship between Social Anxiety and Body Dysmorphic Concerns

PubMed Central

Fang, Angela; Asnaani, Anu; Gutner, Cassidy; Cook, Courtney; Wilhelm, Sabine; Hofmann, Stefan G.

2011-01-01

The goal of this study was to examine the role of rejection sensitivity in the relationship between social anxiety and body dysmorphic concerns. To test our hypothesis that rejection sensitivity mediates the link between social anxiety and body dysmorphic concerns, we administered self-report questionnaires to 209 student volunteers. Consistent with our prediction, rejection sensitivity partially mediated the relationship between social anxiety symptoms and body dysmorphic concerns. The implications of the overlap between these constructs are discussed. PMID:21741203

Intravenous immunoglobulin in kidney transplantation.

PubMed

Tedla, Fasika M; Roche-Recinos, Andrea; Brar, Amarpali

2015-12-01

Antibody-mediated injury of renal allografts has assumed increasing importance with the availability of potent immunosuppressants directed against T-lymphocytes. Intravenous immunoglobulin (IVIG) has been used for prevention and treatment of antibody-mediated rejection. The review summarizes recent advances that shed light on mechanisms of action of IVIG and outlines current roles of IVIG in kidney transplantation. Observational studies support the use of IVIG for desensitization and treatment of acute rejection. Most studies are small and uncontrolled, but a matched case-control study reported a better survival with incompatible live-donor kidney transplant after desensitization using IVIG-containing regimens compared with dialysis or waiting for compatible transplant. Recent data indicate that variations in glycosylation and amino acid sequence cause the crystallizable fragment of immunoglobulin G to assume specific conformations that have high affinity for canonical crystallizable fragment receptors (FcR) or a newly discovered class of FcRs, labelled type II FcRs. Signaling through type II FcRs appears to trigger anti-inflammatory pathways. Recent discoveries expand our understanding of the mechanism of action of IVIG. Future research is expected to clarify the relevance of these findings to humans and could lead to the development of novel immunomodulatory agents.

Self-Silencing and Rejection Sensitivity in Adolescent Romantic Relationships

ERIC Educational Resources Information Center

Harper, Melinda S.; Dickson, Joseph W.; Welsh, Deborah P.

2006-01-01

This study examined the link between rejection sensitivity, self-silencing behaviors, and depressive symptomatology among adolescent dating couples. Self-silencing was hypothesized to be the process mediating the association between rejection sensitivity and depressive symptoms. Our sample included 211 couples between 14 and 21 who were dating at…

Paying To Belong: When Does Rejection Trigger Ingratiation?

PubMed Central

Romero-Canyas, Rainer; Downey, Geraldine; Reddy, Kavita S.; Rodriguez, Sylvia; Cavanaugh, Timothy J.; Pelayo, Rosemary

2010-01-01

Societies and social scientists have long held the belief that exclusion induces ingratiation and conformity, an idea in contradiction with robust empirical evidence linking rejection with hostility and aggression. The classic literatures on ingratiation and conformity help resolve this contradiction by identifying circumstances under which rejection may trigger efforts to ingratiate. Jointly, findings from these literatures suggest that when people are given an opportunity to impress their rejecters, ingratiation is likely after rejection experiences that are harsh and that occur in important situations that threaten the individual’s self-definition. Four studies tested the hypothesis that people high in rejection sensitivity, and therefore dispositionally concerned about rejection, will utilize opportunities to ingratiate after harsh rejection in situations that are self-defining. In three studies of situations that are particularly self-defining for men, rejection predicted ingratiation among men (but not women) who were high in rejection sensitivity. In a fourth study, harsh rejection in a situation particularly self-defining for women predicted ingratiation among highly rejection-sensitive women (but not men). These findings help identify the specific circumstances under which people are willing to act in socially desirable ways toward those who have rejected them harshly. PMID:20649367

History of Abuse and Risky Sex among Substance Users: The Role of Rejection Sensitivity and the Need to Belong

PubMed Central

Woerner, Jacqueline; Kopetz, Catalina; Lechner, William V.; Lejuez, Carl

2016-01-01

This study investigates abuse and rejection sensitivity as important correlates of risky sexual behavior in the context of substance use. Victims of abuse may experience heightened sensitivity to acute social rejection and consequently engage in risky sexual behavior in an attempt to restore belonging. Data were collected from 258 patients at a substance use treatment facility in Washington, D.C. Participants' history of abuse and risky sexual behavior were assessed via self-report. To test the mediating role of rejection sensitivity, participants completed a social rejection task (Cyberball) and responded to a questionnaire assessing their reaction to the rejection experience. General risk-taking propensity was assessed using a computerized lab measure. Abuse was associated with increased rejection sensitivity (B = .124, SE = .040, p = .002), which was in turn associated with increased risky sex (B = .06, SE = .028, p = .03) (indirect effect = .0075, SE = .0043; 95% CI [.0006, 0.0178]), but not with other indices of risk-taking. These findings suggest that rejection sensitivity may be an important mechanism underlying the relationship between abuse and risky sexual behavior among substance users. These effects do not extend to other risk behaviors, supporting the notion that risky sex associated with abuse represents a means to interpersonal connection rather than a general tendency toward self-defeating behavior. PMID:27344009

Rejection Sensitivity in Late Adolescence: Social and Emotional Sequelae

ERIC Educational Resources Information Center

Marston, Emily G.; Hare, Amanda; Allen, Joseph P.

2010-01-01

This study used longitudinal, multireporter data, in a community sample, to examine the role of rejection sensitivity in late adolescents' social and emotional development. Rejection sensitivity was linked to a relative increase in adolescent depressive and anxiety symptoms over a 3-year period, even after accounting for teens' baseline level of…

Genetic and clinical risk factors of new-onset diabetes after transplantation in Hispanic kidney transplant recipients.

PubMed

Yang, Jaewook; Hutchinson, Ian I; Shah, Tariq; Min, David I

2011-05-27

New-onset diabetes after transplantation (NODAT) is one of the major complications after transplantation and is associated with reduced overall patient and graft survival. The objective of this study was to determine the genetic and clinical risk factors for NODAT in Hispanic kidney transplant recipients. Hispanic kidney allograft recipients without evidence of preexisting diabetes who developed NODAT (n=133) were studied using Hispanic kidney transplant recipients with no evidence of diabetes as a control group (n=170). NODAT was defined as fasting glucose levels ≥126 mg/dL on two or more occasions or patients taking any insulin or oral hypoglycemic agents 1 month or later after kidney transplantation. Fourteen alleles in nine genes were genotyped and other patients' clinical data with genotype data were analyzed by logistic regression. Among 14 alleles, hepatocyte nuclear factor 4 alpha (HNF4A) AA (rs2144908, odds ratio [OR]=1.96, confidence interval [CI]=1.08-3.50, P=0.010), HNF4A TT (rs1884614, OR=2.44, CI=1.42-4.48, P=0.002), and insulin receptor substrate 1 AA+AG (rs1801278, OR=2.71, CI=1.16-6.89, P=0.021) remained significant after logistic regression. Among the clinical factors, average age (OR=1.01, CI=1.00-1.08, P=0.048), sirolimus (OR=5.36, CI=3.02-10.4, P=0.001), deceased donor (OR=1.96, CI=1.16-2.94, P=0.015), and acute rejection (OR=2.92, CI=1.31-5.77, P=0.009) remained significant after logistic regression. This study indicates that polymorphism of two alleles of HNF-4A gene (rs2144908 and rs1884614) and insulin receptor substrate 1 (rs1801278) are significantly associated with NODAT in kidney transplant patients with Hispanic ethnicity. In the case of clinical factors, older age (>50 year), deceased donor type, acute rejection, and sirolimus use are associated with NODAT in Hispanic kidney transplant recipients.

Obese ZDF rats fermented resistant starch with effects on gut microbiota but no reduction in abdominal fat.

PubMed

Goldsmith, Felicia; Guice, Justin; Page, Ryan; Welsh, David A; Taylor, Christopher M; Blanchard, Eugene E; Luo, Meng; Raggio, Anne M; Stout, Rhett W; Carvajal-Aldaz, Diana; Gaither, Amanda; Pelkman, Christine; Ye, Jianping; Martin, Roy J; Geaghan, James; Durham, Holiday A; Coulon, Diana; Keenan, Michael J

2017-01-01

To determine if whole-grain (WG) flour with resistant starch (RS) will produce greater fermentation than isolated RS in obese Zucker Diabetic Fatty (ZDF) rats, and whether greater fermentation results in different microbiota, reduced abdominal fat, and increased insulin sensitivity. This study utilized four groups fed diets made with either isolated digestible control starch, WG control flour (6.9% RS), isolated RS-rich corn starch (25% RS), or WG corn flour (25% RS). ZDF rats fermented RS and RS-rich WG flour to greatest extent among groups. High-RS groups had increased serum glucagon-like peptide 1 (GLP-1) active. Feeding isolated RS showed greater Bacteroidetes to Firmicutes phyla among groups, and rats consuming low RS diets possessed more bacteria in Lactobacillus genus. However, no differences in abdominal fat were observed, but rats with isolated RS had greatest insulin sensitivity among groups. Data demonstrated ZDF rats (i) possess a microbiota that fermented RS, and (ii) WG high-RS fermented better than purified RS. However, fermentation and microbiota changes did not translate into reduced abdominal fat. The defective leptin receptor may limit ZDF rats from responding to increased GLP-1 and different microbiota for reducing abdominal fat, but did not prevent improved insulin sensitivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resilience and rejection sensitivity mediate long-term outcomes of parental divorce.

PubMed

Schaan, Violetta K; Vögele, Claus

2016-11-01

Increasing divorce rates leave more and more children to deal with the separation of their parents. Recent research suggests that children of divorced parents more often experience psychological and physical symptoms than children of non-divorced parents. The processes that mediate the relationship between parental divorce and ill-health, however, are still elusive. This study investigated the mediating role of psychological factors such as resilience and rejection sensitivity on the long-term consequences of parental divorce in young adults. One hundred and ninety-nine participants (mean age 22.3 years) completed an online survey, including measures of mental health, childhood trauma, resilience, and rejection sensitivity. Participants with divorced parents (33 %) reported increased levels of psychological symptoms, childhood trauma, rejection sensitivity, and lower levels of resilience. The association between parental divorce and mental health was fully mediated by resilience, rejection sensitivity, and childhood trauma. The mediation model explained up to 44 % of the total variance in mental health symptoms. Resilience and rejection sensitivity are crucial factors for successful coping with the experience of parental separation. Prevention programs that help to boost children's resilience might help to reduce the long-term effects of parental divorce on their attachment style (e.g., rejection sensitivity), thereby improving their mental health on the long run. Furthermore, the results call for parental awareness and counseling to target and reduce the observed increased level of childhood trauma. Limitations concern the cross-sectional and retrospective design of the study.

Rejection Sensitivity, Perceived Power, and HIV Risk in the Relationships of Low-Income Urban Women.

PubMed

Berenson, Kathy R; Paprocki, Christine; Thomas Fishman, Marget; Bhushan, Devika; El-Bassel, Nabila; Downey, Geraldine

2015-01-01

The psychological processes associated with HIV infection in long-term relationships differ from those operative in casual sexual encounters, and relatively little research has considered the aspects of personality applicable in the ongoing heterosexual relationships in which women are at greatest risk. Sensitivity to rejection has been linked with efforts to prevent rejection at a cost to the self and, therefore, may be relevant to the health risks that many women incur in relationships. We examined the association of rejection sensitivity with women's sexual risk behavior in a sample of women at heightened risk for HIV exposure. Women in long-term heterosexual relationships (N = 159) were recruited for study participation in the hospital emergency room serving a low-income neighborhood in New York City, in 2001-2003. Rejection sensitivity and known HIV risk factors were assessed using verbally administered questionnaires. Rejection sensitivity was associated with lower perceived relationship power and, in turn, more frequent unprotected sex with a partner perceived to be at risk for HIV. These results held when controlling for other HIV risk factors including partner violence, economic dependence, and substance use. Understanding the association of rejection concerns with lower perceived personal power in relationships may be important for HIV prevention.

Rejection Sensitivity, Perceived Power and HIV Risk in the Relationships of Low-Income Urban Women

PubMed Central

Berenson, Kathy R.; Paprocki, Christine; Fishman, Marget Thomas; Bhushan, Devika; El-Bassel, Nabila; Downey, Geraldine

2016-01-01

The psychological processes associated with HIV infection in long-term relationships differ from those operative in casual sexual encounters, and relatively little research has considered the aspects of personality applicable in the ongoing heterosexual relationships in which women are at greatest risk. Sensitivity to rejection has been linked with efforts to prevent rejection at a cost to the self and therefore may be relevant to the health risks that many women incur in relationships. We examined the association of rejection sensitivity with women’s sexual risk behavior in a sample of women at heightened risk for HIV exposure. Women in long-term heterosexual relationships (N = 159) were recruited for study participation in the hospital emergency room serving a low-income neighborhood in New York City, in 2001–2003. Rejection sensitivity and known HIV risk factors were assessed using verbally administered questionnaires. Rejection sensitivity was associated with lower perceived relationship power and in turn, more frequent unprotected sex with a partner perceived to be at risk for HIV. These results held when controlling for other HIV risk factors including partner violence, economic dependence, and substance use. Understanding the association of rejection concerns with lower perceived personal power in relationships may be important for HIV prevention. PMID:26086275

High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant.

PubMed

Patel, Parag C; Hill, Douglas A; Ayers, Colby R; Lavingia, Bhavna; Kaiser, Patricia; Dyer, Adrian K; Barnes, Aliessa P; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Stastny, Peter; Ring, W Steves; de Lemos, James A; Drazner, Mark H

2014-05-01

A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance. © 2014 American Heart Association, Inc.

Remembering rejection: specificity and linguistic styles of autobiographical memories in borderline personality disorder and depression.

PubMed

Rosenbach, Charlotte; Renneberg, Babette

2015-03-01

High levels of rejection sensitivity are assumed to be the result of early and prolonged experiences of rejection. Aim of this study was to investigate autobiographical memories of rejection in clinical samples high in rejection sensitivity (Borderline Personality Disorder, BPD, and Major Depressive Disorder, MDD) and to identify group differences in the quality of the memories. Memories of rejection were retrieved using an adapted version of the Autobiographical Memory Test (AMT; five positive cue words, five cue words referring to rejection). Specificity of memories and linguistic word usage was analyzed in 30 patients with BPD, 27 patients with MDD and 30 healthy controls. Patients with BPD retrieved less specific memories compared to the healthy control group, whereas patients with MDD did not differ from controls in this regard. The group difference was no longer significant when controlling for rejection sensitivity. Linguistic analysis indicated that compared to both other groups, patients with BPD showed a higher self-focus, used more anger-related words, referred more frequently to social environments, and rated memories of rejection as more relevant for today's life. Clinical symptoms were not assessed in the control group. Moreover, the written form of the AMT might reduce the total number of specific memories. The level of rejection sensitivity influenced the specificity of the retrieved memories. Analysis of linguistic styles revealed specific linguistic patterns in BPD compared to non-clinical as well as depressed participants. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Perfect Storm: HLA Antibodies, Complement, FcγRs and Endothelium in Transplant Rejection

PubMed Central

Thomas, Kimberly A.; Valenzuela, Nicole M.; Reed, Elaine F.

2015-01-01

The pathophysiology of antibody-mediated rejection (AMR) in solid organ transplants is multi-faceted and predominantly caused by antibodies directed against polymorphic donor human leukocyte antigens (HLA). Despite the clearly detrimental impact of HLA antibodies (HLA-Ab) on graft function and survival, the prevention, diagnosis and treatment of AMR remain a challenge. Histological manifestations of AMR reflect signatures of HLA-Ab-triggered injury, specifically endothelial changes, recipient leukocytic infiltrate, and complement deposition. We review the interconnected mechanisms of HLA-Ab-mediated injury that might synergize in a “perfect storm” of inflammation. Characterization of antibody features that are critical for effector functions may help identify HLA-Ab more likely to cause rejection. We also highlight recent advancements that may pave the way for new, more effective therapeutics. PMID:25801125

Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia

PubMed Central

Vargas-Alarcón, Gilberto; Fragoso, José-Manuel; Cruz-Robles, David; Vargas, Angélica; Vargas, Alfonso; Lao-Villadóniga, José-Ignacio; García-Fructuoso, Ferrán; Ramos-Kuri, Manuel; Hernández, Fernando; Springall, Rashidi; Bojalil, Rafael; Vallejo, Maite; Martínez-Lavín, Manuel

2007-01-01

Autonomic dysfunction is frequent in patients with fibromyalgia (FM). Heart rate variability analyses have demonstrated signs of ongoing sympathetic hyperactivity. Catecholamines are sympathetic neurotransmitters. Catechol-O-methyltransferase (COMT), an enzyme, is the major catecholamine-clearing pathway. There are several single-nucleotide polymorphisms (SNPs) in the COMT gene associated with the different catecholamine-clearing abilities of the COMT enzyme. These SNPs are in linkage disequilibrium and segregate as 'haplotypes'. Healthy females with a particular COMT gene haplotype (ACCG) producing a defective enzyme are more sensitive to painful stimuli. The objective of our study was to define whether women with FM, from two different countries (Mexico and Spain), have the COMT gene haplotypes that have been previously associated with greater sensitivity to pain. All the individuals in the study were female. Fifty-seven Mexican patients and 78 Spanish patients were compared with their respective healthy control groups. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Six COMT SNPs (rs2097903, rs6269, rs4633, rs4818, rs4680, and rs165599) were genotyped from peripheral blood DNA. In Spanish patients, there was a significant association between three SNPs (rs6269, rs4818, and rs4680) and the presence of FM when compared with healthy controls. Moreover, in Spanish patients with the 'high pain sensitivity' haplotype (ACCG), the disease, as assessed by the FIQ, was more severe. By contrast, Mexican patients displayed only a weak association between rs6269 and rs165599, and some FIQ subscales. In our group of Spanish patients, there was an association between FM and the COMT haplotype previously associated with high pain sensitivity. This association was not observed in Mexican patients. Studies with a larger sample size are needed in order to verify or amend these preliminary results. PMID:17961261

Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion.

PubMed

Heni, Martin; Haupt, Axel; Schäfer, Silke A; Ketterer, Caroline; Thamer, Claus; Machicao, Fausto; Stefan, Norbert; Staiger, Harald; Häring, Hans-Ulrich; Fritsche, Andreas

2010-06-09

Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, beta-cell dysfunction, or glucose intolerance. We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within PCSK1. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp. The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p >or= 0.07). Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUCproinsulin and AUCproinsulin/AUCinsulin (rs6235: p(additive) model or= 0.08). The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (pdom

Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion

PubMed Central

2010-01-01

Background Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, β-cell dysfunction, or glucose intolerance. Methods We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within PCSK1. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp. Results The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p ≥ 0.07). Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUCproinsulin and AUCproinsulin/AUCinsulin (rs6235: padditive model ≤ 0.009, effect sizes 8/8%, rs6232: pdominant model ≤ 0.01, effect sizes 10/21%). Insulin secretion was not affected by the variants (different secretion parameters, all p ≥ 0.08). The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (pdom ≤ 0.0047), 4.5% lower HOMAIR (pdom = 0.02) and 3.5% lower 120-min glucose (pdom = 0.0003) independently of BMI and proinsulin conversion. SNP rs6235 was not associated with parameters of glucose metabolism. Conclusions Like rare mutations in PCSK1, the more common variants tested determine glucose-stimulated proinsulin conversion, but not insulin secretion. In addition, rs6232, encoding the amino acid exchange N221D, influences insulin sensitivity and glucose homeostasis. PMID:20534142

Delay discounting, risk-taking, and rejection sensitivity among individuals with Internet and Video Gaming Disorders.

PubMed

Weinstein, Aviv; Abu, Hodaya Ben; Timor, Ayelet; Mama, Yaniv

2016-12-01

Background and aims There is a previous evidence for impulsivity in individuals with Internet and Video Gaming Disorders. The aim of this study was to examine whether Internet and video game addictions are associated with experiential delay discounting, risk-taking, and sensitivity to social rejection using computerized tasks and questionnaires. Methods Twenty participants (mean age 24, SD = 1.55) with high score on the Problematic Online Gaming Questionnaire (POGQ) were compared with 20 participants (mean age 24.8, SD = 1.34) with low score on the POGQ. They performed on computerized Balloon Analog Risk Task and Experiential Delay discounting Task (EDT), and filled in the sensitivity to social rejection questionnaire. Results Participants with high POGQ scores had lower measures of delay discounting, higher measures of risk-taking, and higher measures of sensitivity to social rejection compared with participants with low POGQ scores. Discussion The results of this study support the previous evidence of risk-taking and provide new evidence for difficulties in delay discounting and sensitivity to social rejection among those who score high on Internet and video games. Conclusions The results suggest that Internet- and video game-addicted individuals seek immediate gratification and cannot wait for later reward. Furthermore, these individuals spend time in the virtual world, where they feel safe, and avoid social interactions presumably due to fears of social rejection.

Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach.

PubMed

Chen, F S; Kumsta, R; Dvorak, F; Domes, G; Yim, O S; Ebstein, R P; Heinrichs, M

2015-10-27

Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917-rs2268498-rs4564970-rs237897-rs2268495-rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration.

Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach

PubMed Central

Chen, F S; Kumsta, R; Dvorak, F; Domes, G; Yim, O S; Ebstein, R P; Heinrichs, M

2015-01-01

Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917–rs2268498–rs4564970–rs237897–rs2268495–rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration. PMID:26506050

The perfect storm: HLA antibodies, complement, FcγRs, and endothelium in transplant rejection.

PubMed

Thomas, Kimberly A; Valenzuela, Nicole M; Reed, Elaine F

2015-05-01

The pathophysiology of antibody-mediated rejection (AMR) in solid organ transplants is multifaceted and predominantly caused by antibodies directed against polymorphic donor human leukocyte antigens (HLAs). Despite the clearly detrimental impact of HLA antibodies (HLA-Abs) on graft function and survival, the prevention, diagnosis, and treatment of AMR remain a challenge. The histological manifestations of AMR reflect the signatures of HLA-Ab-triggered injury, specifically endothelial changes, recipient leukocytic infiltrate, and complement deposition. We review the interconnected mechanisms of HLA-Ab-mediated injury that might synergize in a 'perfect storm' of inflammation. Characterization of antibody features that are critical for effector functions may help to identify HLA-Abs that are more likely to cause rejection. We also highlight recent advances that may pave the way for new, more effective therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Three Rs of Animal Research: What they Mean for the Institutional Animal Care and Use Committee and Why.

PubMed

Curzer, Howard J; Perry, Gad; Wallace, Mark C; Perry, Dan

2016-04-01

The Institutional Animal Care and Use Committee (IACUC) is entrusted with assessing the ethics of proposed projects prior to approval of animal research. The role of the IACUC is detailed in legislation and binding rules, which are in turn inspired by the Three Rs: the principles of Replacement, Reduction, and Refinement. However, these principles are poorly defined. Although this provides the IACUC leeway in assessing a proposed project, it also affords little guidance. Our goal is to provide procedural and philosophical clarity to the IACUC without mandating a particular outcome. To do this, we analyze the underlying logic of the Three Rs and conclude that the Three Rs accord animals moral standing, though not necessarily "rights" in the philosophical sense. We suggest that the Rs are hierarchical, such that Replacement, which can totally eliminate harm, should be considered prior to Reduction, which decreases the number of animals harmed, with Refinement being considered last. We also identify the need for a hitherto implicit fourth R: Reject, which allows the IACUC to refuse permission for a project which does not promise sufficient benefit to offset the pain and distress likely to be caused by the proposed research.

Association of SNPs with the efficacy and safety of immunosuppressant therapy after heart transplantation.

PubMed

Sánchez-Lázaro, Ignacio; Herrero, María José; Jordán-De Luna, Consuelo; Bosó, Virginia; Almenar, Luis; Rojas, Luis; Martínez-Dolz, Luis; Megías-Vericat, Juan E; Sendra, Luis; Miguel, Antonio; Poveda, José L; Aliño, Salvador F

2015-01-01

Studying the possible influence of SNPs on efficacy and safety of calcineurin inhibitors upon heart transplantation. In 60 heart transplant patients treated with tacrolimus or cyclosporine, we studied a panel of 36 SNPs correlated with a series of clinical parameters during the first post-transplantation year. The presence of serious infections was correlated to ABCB1 rs1128503 (p = 0.012), CC genotype reduced the probability of infections being also associated with lower blood cyclosporine concentrations. Lower renal function levels were found in patients with rs9282564 AG (p = 0.003), related to higher blood cyclosporine blood levels. A tendency toward increased graft rejection (p = 0.05) was correlated to rs2066844 CC in NOD2/CARD15, a gene related to lymphocyte activation. Pharmacogenetics can help identify patients at increased risk of clinical complications. Original submitted 30 January 2015; revision submitted 27 March 2015.

Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery

PubMed Central

Muraoka, Wataru; Nishizawa, Daisuke; Fukuda, Kenichi; Kasai, Shinya; Hasegawa, Junko; Wajima, Koichi; Nakagawa, Taneaki

2016-01-01

Background Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment. PMID:28256933

Repression-Sensitization and Health Behavior.

ERIC Educational Resources Information Center

Gayton, William F.; And Others

1978-01-01

Examined relationship between repression-sensitization (R-S) and visits to prison infirmary for males during a one-year period. Main effect for R-S dimension was significant for total number of visits, number of medically justified visits, and number of medically unjustified visits. Sensitizers had significantly more visits than repressors.…

Structure-function correlations using scanning laser polarimetry in primary angle-closure glaucoma and primary open-angle glaucoma.

PubMed

Lee, Pei-Jung; Liu, Catherine Jui-Ling; Wojciechowski, Robert; Bailey-Wilson, Joan E; Cheng, Ching-Yu

2010-05-01

To assess the correlations between retinal nerve fiber layer (RNFL) thickness measured with scanning laser polarimetry and visual field (VF) sensitivity in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Prospective, comparative, observational cases series. Fifty patients with POAG and 56 patients with PACG were examined using scanning laser polarimetry with variable corneal compensation (GDx VCC; Laser Diagnostic Technologies, Inc.) and Humphrey VF analyzer (Carl Zeiss Meditec, Inc.) between August 2005 and July 2006 at Taipei Veterans General Hospital. Correlations between RNFL thickness and VF sensitivity, expressed as mean sensitivity in both decibel and 1/Lambert scales, were estimated by the Spearman rank correlation coefficient (r(s)) and multivariate median regression models (pseudo R(2)). The correlations were determined globally and for 6 RNFL sectors and their corresponding VF regions. The correlation between RNFL thickness and mean sensitivity (in decibels) was weaker in the PACG group (r(s) = 0.38; P = .004; pseudo R(2) = 0.17) than in the POAG group (r(s) = 0.51; P < .001; pseudo R(2) = .31), but the difference in the magnitude of correlation was not significant (P = .42). With Bonferroni correction, the structure-function correlation was significant in the superotemporal (r(s) = 0.62), superonasal (r(s) = 0.56), inferonasal (r(s) = 0.53), and inferotemporal (r(s) = 0.50) sectors in the POAG group (all P < .001), whereas it was significant only in the superotemporal (r(s) = 0.53) and inferotemporal (r(s) = 0.48) sectors in the PACG group (both P < .001). The results were similar when mean sensitivity was expressed as 1/Lambert scale. Both POAG and PACG eyes had moderate structure-function correlations using scanning laser polarimetry. Compared with eyes with POAG, fewer RNFL sectors have significant structure-function correlations in eyes with PACG. Copyright 2010 Elsevier Inc. All rights reserved.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies.

PubMed

Alelign, Tilahun; Ahmed, Momina M; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

2018-01-01

Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

Revisiting Traditional Risk Factors for Rejection and Graft Loss after Kidney Transplantation

PubMed Central

Dunn, TB; Noreen, H; Gillingham, K; Maurer, D; Ozturk, O. Goruroglu; Pruett, TL; Bray, RA; Gebel, HM; Matas, AJ

2011-01-01

Single antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and SAB testing of day of transplant serum as 1) unsensitized; PRA=0 (n= 178), 2) 3rd party sensitized; no DSA (n=363), or 3) donor sensitized; with DSA (n=46), and studied rejection rates, death censored graft survival (DCGS), and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p<0.0001), but not with PRA in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p<0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p=0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. PMID:21812918

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

PubMed Central

Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

2018-01-01

Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

Community structure analysis of rejection sensitive personality profiles: A common neural response to social evaluative threat?

PubMed

Kortink, Elise D; Weeda, Wouter D; Crowley, Michael J; Gunther Moor, Bregtje; van der Molen, Melle J W

2018-06-01

Monitoring social threat is essential for maintaining healthy social relationships, and recent studies suggest a neural alarm system that governs our response to social rejection. Frontal-midline theta (4-8 Hz) oscillatory power might act as a neural correlate of this system by being sensitive to unexpected social rejection. Here, we examined whether frontal-midline theta is modulated by individual differences in personality constructs sensitive to social disconnection. In addition, we examined the sensitivity of feedback-related brain potentials (i.e., the feedback-related negativity and P3) to social feedback. Sixty-five undergraduate female participants (mean age = 19.69 years) participated in the Social Judgment Paradigm, a fictitious peer-evaluation task in which participants provided expectancies about being liked/disliked by peer strangers. Thereafter, they received feedback signaling social acceptance/rejection. A community structure analysis was employed to delineate personality profiles in our data. Results provided evidence of two subgroups: one group scored high on attachment-related anxiety and fear of negative evaluation, whereas the other group scored high on attachment-related avoidance and low on fear of negative evaluation. In both groups, unexpected rejection feedback yielded a significant increase in theta power. The feedback-related negativity was sensitive to unexpected feedback, regardless of valence, and was largest for unexpected rejection feedback. The feedback-related P3 was significantly enhanced in response to expected social acceptance feedback. Together, these findings confirm the sensitivity of frontal midline theta oscillations to the processing of social threat, and suggest that this alleged neural alarm system behaves similarly in individuals that differ in personality constructs relevant to social evaluation.

The influence of structural stigma and rejection sensitivity on young sexual minority men's daily tobacco and alcohol use

PubMed Central

Pachankis, John E.; Hatzenbuehler, Mark L.; Starks, Tyrel J.

2018-01-01

Stigma occurs at both individual and structural levels, but existing research tends to examine the effect of individual and structural forms of stigma in isolation, rather than considering potential synergistic effects. To address this gap, our study examined whether stigma at the individual level, namely gay-related rejection sensitivity, interacts with structural stigma to predict substance use among young sexual minority men. Sexual minority (n = 119) participants completed online measures of our constructs (e.g., rejection sensitivity). Participants currently resided across a broad array of geographic areas (i.e., 24 U.S. states), and had attended high school in 28 states, allowing us to capture sufficient variance in current and past forms of structural stigma, defined as (1) a lack of state-level policies providing equal opportunities for heterosexual and sexual minority individuals and (2) negative state-aggregated attitudes toward sexual minorities. To measure daily substance use, we utilized a daily diary approach, whereby all participants were asked to indicate whether they used tobacco or alcohol on nine consecutive days. Results indicated that structural stigma interacted with rejection sensitivity to predict tobacco and alcohol use, and that this relationship depended on the developmental timing of exposure to structural stigma. In contrast, rejection sensitivity did not mediate the relationship between structural stigma and substance use. These results suggest that psychological predispositions, such as rejection sensitivity, interact with features of the social environment, such as structural stigma, to predict important health behaviors among young sexual minority men. These results add to a growing body of research documenting the multiple levels through which stigma interacts to produce negative health outcomes among sexual minority individuals. PMID:24507912

Low soil moisture during hot periods drives apparent negative temperature sensitivity of soil respiration in a dryland ecosystem: A multi-model comparison

USGS Publications Warehouse

Tucker, Colin; Reed, Sasha C.

2016-01-01

Arid and semiarid ecosystems (drylands) may dominate the trajectory of biosphere-to-atmosphere carbon (C) flux over the coming century. Accordingly, understanding dryland CO2 efflux controls is important for understanding C cycling at the global-scale: key unknowns regarding how temperature and moisture interact to regulate dryland C cycling remain. Further, the patchiness of dryland vegetation can create ‘islands of fertility’, with spatially heterogeneous rates of soil respiration (Rs). At our study site in southeastern Utah, USA we added or removed litter (0 to 650% of control) in paired plots that were either associated with a shrub or with interspaces between vascular plants. We measured Rs, soil temperature, and water content (θ) on eight sampling dates between October 2013 and November 2014. Rs was highest following monsoon rains in late summer when soil temperature was ~30°C. During mid-summer, Rs was low, associated with high soil temperatures (>40°C), resulting in an apparent negative temperature sensitivity of Rs at high temperatures, and positive temperature sensitivity at low-moderate temperatures. We used Bayesian statistical methods to compare multiple competing models capturing a wide range of hypothesized relationships between temperature, moisture, and Rs. The best fit model indicates apparent negative temperature sensitivity of soil respiration at high temperatures reflects the control of soil moisture – not high temperatures – in limiting Rs. The modeled Q10 ranged from 2.7 at 5°C to 1.4 at 45°C. Litter addition had no effect on temperature sensitivity or reference respiration (Rref = Rs at 20°C and optimum moisture) beneath shrubs, and little effect on Rref in interspaces, yet Rref was 1.5 times higher beneath shrubs than in interspaces. Together, these results suggest reduced Rs often observed at high temperatures in drylands is dominated by the control of moisture, and that variable litter inputs – at least over the short-term – exert minimal control over Rs.

When rejection sensitivity matters: regulating dependence within daily interactions with family and friends.

PubMed

Overall, Nickola C; Sibley, Chris G

2009-08-01

This diary study examined situational dependence within daily interactions with family members and close friends over a 2-week period. Experiencing low personal control (high situational dependence) when interacting with family members and friends was associated with lower perceived regard and intimacy. Participants generally regulated felt dependence by derogating and withdrawing from their interaction partner (self-protective dependence regulation) and exhibiting lower levels of positive behavior, such as expressing thoughts and feelings or trying to improve the interaction (relationship-promotive dependence regulation). Furthermore, higher rejection sensitivity (but not low self-esteem) was associated with more negative evaluations of perceived regard and intimacy, greater self-protective dependence regulation, and lower relationship-promotive dependence regulation within low control interactions. These results identify dependence as a key element of rejection risk contexts and support the situation-specific nature of rejection sensitivity.

Variation in the TAS1R2 Gene, Sweet Taste Perception and Intake of Sugars.

PubMed

Dias, Andre G; Eny, Karen M; Cockburn, Moira; Chiu, Winnie; Nielsen, Daiva E; Duizer, Lisa; El-Sohemy, Ahmed

2015-01-01

To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake. Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796). Sucrose taste thresholds were determined by staircase procedure (solutions: 9 × 10-6 to 0.5 mol/l). Suprathreshold sensitivity to 0.01-1.0 mol/l sucrose solutions was assessed using general Labeled Magnitude Scales. A significant genotype-BMI interaction was observed for rs12033832 (G>A) for suprathreshold sensitivity (p = 0.01) and sugar intake (p = 0.003). Among participants with a BMI ≥25, G allele carriers had lower sensitivity ratings (mean incremental area under the taste sensitivity curve ± SE; GG/GA 54.4 ± 4.1 vs. AA 178.5 ± 66.6; p = 0.006), higher thresholds (GG/GA 9.3 ± 1.1 vs. AA 4.4 ± 4.3 mmol/l; p = 0.004) and consumed more sugars (GG/GA 130 ± 4 vs. AA 94 ± 13 g/day; p = 0.009). G allele carriers with a BMI <25 had lower thresholds (GG/GA 8.6 ± 0.5 vs. AA 16.7 ± 5.7 mmol/l; p = 0.02) and consumed less sugars (GG/GA 122 ± 2 vs. AA 145 ± 8 g/day; p = 0.004). The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI. © 2015 S. Karger AG, Basel.

Efficacy of increased resistant starch consumption in human type 2 diabetes.

PubMed

Bodinham, C L; Smith, L; Thomas, E L; Bell, J D; Swann, J R; Costabile, A; Russell-Jones, D; Umpleby, A M; Robertson, M D

2014-01-01

Resistant starch (RS) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome, but its effects on human type 2 diabetes (T2DM) are unknown. This study aimed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postprandial metabolites and body fat in T2DM. Seventeen individuals with well-controlled T2DM (HbA1c 46.6±2 mmol/mol) consumed, in a random order, either 40 g of type 2 RS (HAM-RS2) or a placebo, daily for 12 weeks with a 12-week washout period in between. AT THE END OF EACH INTERVENTION PERIOD, PARTICIPANTS ATTENDED FOR THREE METABOLIC INVESTIGATIONS: a two-step euglycemic-hyperinsulinemic clamp combined with an infusion of [6,6-(2)H2] glucose, a meal tolerance test (MTT) with arterio-venous sampling across the forearm, and whole-body imaging. HAM-RS2 resulted in significantly lower postprandial glucose concentrations (P=0.045) and a trend for greater glucose uptake across the forearm muscle (P=0.077); however, there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity, or on HbA1c. Fasting non-esterified fatty acid (NEFA) concentrations were significantly lower (P=0.004) and NEFA suppression was greater during the clamp with HAM-RS2 (P=0.001). Fasting triglyceride (TG) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 (P=0.039 and P=0.027 respectively). Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption (P=0.049), postprandial GLP1 excursions during the MTT were significantly greater (P=0.009). HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM, but demonstrated beneficial effects on meal handling, possibly due to higher postprandial GLP1.

Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.

PubMed

Xie, Weijia; Wood, Andrew R; Lyssenko, Valeriya; Weedon, Michael N; Knowles, Joshua W; Alkayyali, Sami; Assimes, Themistocles L; Quertermous, Thomas; Abbasi, Fahim; Paananen, Jussi; Häring, Hans; Hansen, Torben; Pedersen, Oluf; Smith, Ulf; Laakso, Markku; Dekker, Jacqueline M; Nolan, John J; Groop, Leif; Ferrannini, Ele; Adam, Klaus-Peter; Gall, Walter E; Frayling, Timothy M; Walker, Mark

2013-06-01

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites-glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)-and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits.

Segregation of face sensitive areas within the fusiform gyrus using global signal regression? A study on amygdala resting-state functional connectivity.

PubMed

Kruschwitz, Johann D; Meyer-Lindenberg, Andreas; Veer, Ilya M; Wackerhagen, Carolin; Erk, Susanne; Mohnke, Sebastian; Pöhland, Lydia; Haddad, Leila; Grimm, Oliver; Tost, Heike; Romanczuk-Seiferth, Nina; Heinz, Andreas; Walter, Martin; Walter, Henrik

2015-10-01

The application of global signal regression (GSR) to resting-state functional magnetic resonance imaging data and its usefulness is a widely discussed topic. In this article, we report an observation of segregated distribution of amygdala resting-state functional connectivity (rs-FC) within the fusiform gyrus (FFG) as an effect of GSR in a multi-center-sample of 276 healthy subjects. Specifically, we observed that amygdala rs-FC was distributed within the FFG as distinct anterior versus posterior clusters delineated by positive versus negative rs-FC polarity when GSR was performed. To characterize this effect in more detail, post hoc analyses revealed the following: first, direct overlays of task-functional magnetic resonance imaging derived face sensitive areas and clusters of positive versus negative amygdala rs-FC showed that the positive amygdala rs-FC cluster corresponded best with the fusiform face area, whereas the occipital face area corresponded to the negative amygdala rs-FC cluster. Second, as expected from a hierarchical face perception model, these amygdala rs-FC defined clusters showed differential rs-FC with other regions of the visual stream. Third, dynamic connectivity analyses revealed that these amygdala rs-FC defined clusters also differed in their rs-FC variance across time to the amygdala. Furthermore, subsample analyses of three independent research sites confirmed reliability of the effect of GSR, as revealed by similar patterns of distinct amygdala rs-FC polarity within the FFG. In this article, we discuss the potential of GSR to segregate face sensitive areas within the FFG and furthermore discuss how our results may relate to the functional organization of the face-perception circuit. © 2015 Wiley Periodicals, Inc.

Interrelations of Justice, Rejection, Provocation, and Moral Disgust Sensitivity and Their Links with the Hostile Attribution Bias, Trait Anger, and Aggression

PubMed Central

Bondü, Rebecca; Richter, Philipp

2016-01-01

Several personality dispositions with common features capturing sensitivities to negative social cues have recently been introduced into psychological research. To date, however, little is known about their interrelations, their conjoint effects on behavior, or their interplay with other risk factors. We asked N = 349 adults from Germany to rate their justice, rejection, moral disgust, and provocation sensitivity, hostile attribution bias, trait anger, and forms and functions of aggression. The sensitivity measures were mostly positively correlated; particularly those with an egoistic focus, such as victim justice, rejection, and provocation sensitivity, hostile attributions and trait anger as well as those with an altruistic focus, such as observer justice, perpetrator justice, and moral disgust sensitivity. The sensitivity measures had independent and differential effects on forms and functions of aggression when considered simultaneously and when controlling for hostile attributions and anger. They could not be integrated into a single factor of interpersonal sensitivity or reduced to other well-known risk factors for aggression. The sensitivity measures, therefore, require consideration in predicting and preventing aggression. PMID:27303351

A New Pulse Pileup Rejection Method Based on Position Shift Identification

NASA Astrophysics Data System (ADS)

Gu, Z.; Prout, D. L.; Taschereau, R.; Bai, B.; Chatziioannou, A. F.

2016-02-01

Pulse pileup events degrade the signal-to-noise ratio (SNR) of nuclear medicine data. When such events occur in multiplexed detectors, they cause spatial misposition, energy spectrum distortion and degraded timing resolution, which leads to image artifacts. Pulse pileup is pronounced in PETbox4, a bench top PET scanner dedicated to high sensitivity and high resolution imaging of mice. In that system, the combination of high absolute sensitivity, long scintillator decay time (BGO) and highly multiplexed electronics lead to a significant fraction of pulse pileup, reached at lower total activity than for comparable instruments. In this manuscript, a new pulse pileup rejection method named position shift rejection (PSR) is introduced. The performance of PSR is compared with a conventional leading edge rejection (LER) method and with no pileup rejection implemented (NoPR). A comprehensive digital pulse library was developed for objective evaluation and optimization of the PSR and LER, in which pulse waveforms were directly recorded from real measurements exactly representing the signals to be processed. Physical measurements including singles event acquisition, peak system sensitivity and NEMA NU-4 image quality phantom were also performed in the PETbox4 system to validate and compare the different pulse pile-up rejection methods. The evaluation of both physical measurements and model pulse trains demonstrated that the new PSR performs more accurate pileup event identification and avoids erroneous rejection of valid events. For the PETbox4 system, this improvement leads to a significant recovery of sensitivity at low count rates, amounting to about 1/4th of the expected true coincidence events, compared to the LER method. Furthermore, with the implementation of PSR, optimal image quality can be achieved near the peak noise equivalent count rate (NECR).

Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection.

PubMed

Pelzl, Steffen; Opelz, Gerhard; Daniel, Volker; Wiesel, Manfred; Süsal, Caner

2003-02-15

Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, P<0.0001) (area under the receiver operating characteristic curve 0.96, specificity 100%, sensitivity 88%) and recipients with acute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.

Pain Processing after Social Exclusion and Its Relation to Rejection Sensitivity in Borderline Personality Disorder

PubMed Central

Bungert, Melanie; Koppe, Georgia; Niedtfeld, Inga; Vollstädt-Klein, Sabine; Schmahl, Christian

2015-01-01

Objective There is a general agreement that physical pain serves as an alarm signal for the prevention of and reaction to physical harm. It has recently been hypothesized that “social pain,” as induced by social rejection or abandonment, may rely on comparable, phylogenetically old brain structures. As plausible as this theory may sound, scientific evidence for this idea is sparse. This study therefore attempts to link both types of pain directly. We studied patients with borderline personality disorder (BPD) because BPD is characterized by opposing alterations in physical and social pain; hyposensitivity to physical pain is associated with hypersensitivity to social pain, as indicated by an enhanced rejection sensitivity. Method Twenty unmedicated female BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game (cyberball), with the conditions for exclusion, inclusion, and a control condition with predefined game rules. Each cyberball block was followed by a temperature stimulus (with a subjective pain intensity of 60% in half the cases). The cerebral responses were measured by functional magnetic resonance imaging. The Adult Rejection Sensitivity Questionnaire was used to assess rejection sensitivity. Results Higher temperature heat stimuli had to be applied to BPD patients relative to HCs to reach a comparable subjective experience of painfulness in both groups, which suggested a general hyposensitivity to pain in BPD patients. Social exclusion led to a subjectively reported hypersensitivity to physical pain in both groups that was accompanied by an enhanced activation in the anterior insula and the thalamus. In BPD, physical pain processing after exclusion was additionally linked to enhanced posterior insula activation. After inclusion, BPD patients showed reduced amygdala activation during pain in comparison with HC. In BPD patients, higher rejection sensitivity was associated with lower activation differences during pain processing following social exclusion and inclusion in the insula and in the amygdala. Discussion Despite the similar behavioral effects in both groups, BPD patients differed from HC in their neural processing of physical pain depending on the preceding social situation. Rejection sensitivity further modulated the impact of social exclusion on neural pain processing in BPD, but not in healthy controls. PMID:26241850

Resistant starch can improve insulin sensitivity independently of the gut microbiota.

PubMed

Bindels, Laure B; Segura Munoz, Rafael R; Gomes-Neto, João Carlos; Mutemberezi, Valentin; Martínez, Inés; Salazar, Nuria; Cody, Elizabeth A; Quintero-Villegas, Maria I; Kittana, Hatem; de Los Reyes-Gavilán, Clara G; Schmaltz, Robert J; Muccioli, Giulio G; Walter, Jens; Ramer-Tait, Amanda E

2017-02-07

Obesity-related diseases, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions in industrialized nations, and dietary interventions for their prevention are therefore important. Resistant starches (RS) improve insulin sensitivity in clinical trials, but the mechanisms underlying this health benefit remain poorly understood. Because RS fermentation by the gut microbiota results in the formation of physiologically active metabolites, we chose to specifically determine the role of the gut microbiota in mediating the metabolic benefits of RS. To achieve this goal, we determined the effects of RS when added to a Western diet on host metabolism in mice with and without a microbiota. RS feeding of conventionalized mice improved insulin sensitivity and redressed some of the Western diet-induced changes in microbiome composition. However, parallel experiments in germ-free littermates revealed that RS-mediated improvements in insulin levels also occurred in the absence of a microbiota. RS reduced gene expression of adipose tissue macrophage markers and altered cecal concentrations of several bile acids in both germ-free and conventionalized mice; these effects were strongly correlated with the metabolic benefits, providing a potential microbiota-independent mechanism to explain the physiological effects of RS. This study demonstrated that some metabolic benefits exerted by dietary RS, especially improvements in insulin levels, occur independently of the microbiota and could involve alterations in the bile acid cycle and adipose tissue immune modulation. This work also sets a precedent for future mechanistic studies aimed at establishing the causative role of the gut microbiota in mediating the benefits of bioactive compounds and functional foods.

Relational Stressors and Depressive Symptoms in Late Adolescence: Rejection Sensitivity as a Vulnerability

ERIC Educational Resources Information Center

Chango, Joanna M.; McElhaney, Kathleen Boykin; Allen, Joseph P.; Schad, Megan M.; Marston, Emily

2012-01-01

The role of rejection sensitivity as a critical diathesis moderating the link between adolescent relational stressors and depressive symptoms was examined using multi-method, multi-reporter data from a diverse community sample of 173 adolescents, followed from age 16 to 18. Relational stressors examined included emotional abuse, maternal behavior…

Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

PubMed Central

Xie, Weijia; Wood, Andrew R.; Lyssenko, Valeriya; Weedon, Michael N.; Knowles, Joshua W.; Alkayyali, Sami; Assimes, Themistocles L.; Quertermous, Thomas; Abbasi, Fahim; Paananen, Jussi; Häring, Hans; Hansen, Torben; Pedersen, Oluf; Smith, Ulf; Laakso, Markku; Dekker, Jacqueline M.; Nolan, John J.; Groop, Leif; Ferrannini, Ele; Adam, Klaus-Peter; Gall, Walter E.; Frayling, Timothy M.; Walker, Mark

2013-01-01

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity–related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites—glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)—and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits. PMID:23378610

Revisiting traditional risk factors for rejection and graft loss after kidney transplantation.

PubMed

Dunn, T B; Noreen, H; Gillingham, K; Maurer, D; Ozturk, O G; Pruett, T L; Bray, R A; Gebel, H M; Matas, A J

2011-10-01

Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Manipulations of extracellular Loop 2 in α1 GlyR ultra-sensitive ethanol receptors (USERs) enhance receptor sensitivity to isoflurane, ethanol, and lidocaine, but not propofol

PubMed Central

Naito, Anna; Muchhala, Karan H.; Trang, Janice; Asatryan, Liana; Trudell, James R.; Homanics, Gregg E.; Alkana, Ronald L.; Davies, Daryl L.

2015-01-01

We recently developed Ultra-Sensitive Ethanol Receptors (USERs) as a novel tool for investigation of single receptor subunit populations sensitized to extremely low ethanol concentrations that do not affect other receptors in the nervous system. To this end, we found that mutations within the extracellular Loop 2 region of glycine receptors (GlyRs) and γ-aminobutyric acid type A receptors (GABAARs) can significantly increase receptor sensitivity to micro-molar concentrations of ethanol resulting in up to a 100-fold increase in ethanol sensitivity relative to wild type (WT) receptors. The current study investigated: 1) Whether structural manipulations of Loop 2 in α1 GlyRs could similarly increase receptor sensitivity to other anesthetics; and 2) If mutations exclusive to the C-terminal end of Loop 2 are sufficient to impart these changes. We expressed α1 GlyR USERs in Xenopus oocytes and tested the effects of three classes of anesthetics, isoflurane (volatile), propofol (intravenous), and lidocaine (local), known to enhance glycine-induced chloride currents using two-electrode voltage clamp electrophysiology. Loop 2 mutations produced a significant 10-fold increase in isoflurane and lidocaine sensitivity, but no increase in propofol sensitivity compared to WT α1 GlyRs. Interestingly, we also found that structural manipulations in the C-terminal end of Loop 2 were sufficient and selective for α1 GlyR modulation by ethanol, isoflurane, and lidocaine. These studies are the first to report the extracellular region of α1 GlyRs as a site of lidocaine action. Overall, the findings suggest that Loop 2 of α1 GlyRs is a key region that mediates isoflurane and lidocaine modulation. Moreover, the results identify important amino acids in Loop 2 that regulate isoflurane, lidocaine, and ethanol action. Collectively, these data indicate the commonality of the sites for isoflurane, lidocaine, and ethanol action, and the structural requirements for allosteric modulation on α1 GlyRs within the extracellular Loop 2 region. PMID:25827497

Clazakizumab in Highly-HLA Sensitized Patients Awaiting Renal Transplant

ClinicalTrials.gov

2018-05-08

Kidney Failure, Chronic; End-Stage Renal Disease; Transplant Glomerulopathy; Transplant;Failure,Kidney; Kidney Transplant Failure and Rejection; Antibody-mediated Rejection; Kidney Transplant; Complications

Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation.

PubMed

Stubendorff, Beatrice; Finke, Stephanie; Walter, Martina; Kniemeyer, Olaf; von Eggeling, Ferdinand; Gruschwitz, Torsten; Steiner, Thomas; Ott, Undine; Wolf, Gunter; Wunderlich, Heiko; Junker, Kerstin

2014-12-01

Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice. Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay. A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity. Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

Inhibition of Arabidopsis growth by the allelopathic compound azetidine-2-carboxylate is due to the low amino acid specificity of cytosolic prolyl-tRNA synthetase.

PubMed

Lee, Jiyeon; Joshi, Naveen; Pasini, Rita; Dobson, Renwick C J; Allison, Jane; Leustek, Thomas

2016-10-01

The toxicity of azetidine-2-carboxylic acid (A2C), a structural analogue of L-proline, results from its incorporation into proteins due to misrecognition by prolyl-tRNA synthetase (ProRS). The growth of Arabidopsis thaliana seedling roots is more sensitive to inhibition by A2C than is cotyledon growth. Arabidopsis contains two ProRS isozymes. AtProRS-Org (At5g52520) is localized in chloroplasts/mitochondria, and AtProRS-Cyt (At3g62120) is cytosolic. AtProRS-Cyt mRNA is more highly expressed in roots than in cotyledons. Arabidopsis ProRS isoforms were expressed as His-tagged recombinant proteins in Escherichia coli. Both enzymes were functionally active in ATP-PPi exchange and aminoacylation assays, and showed similar K m for L-proline. A major difference was observed in the substrate specificity of the two enzymes. AtProRS-Cyt showed nearly identical substrate specificity for L-proline and A2C, but for AtProRS-Org the specificity constant was 77.6 times higher for L-proline than A2C, suggesting that A2C-sensitivity may result from lower amino acid specificity of AtProRS-Cyt. Molecular modelling and simulation results indicate that this specificity difference between the AtProRS isoforms may result from altered modes of substrate binding. Similar kinetic results were obtained with the ProRSs from Zea mays, suggesting that the difference in substrate specificity is a conserved feature of ProRS isoforms from plants that do not accumulate A2C and are sensitive to A2C toxicity. The discovery of the mode of action of A2C toxicity could lead to development of biorational weed management strategies. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Victimization, social anxiety, and body dysmorphic concerns: appearance-based rejection sensitivity as a mediator.

PubMed

Lavell, Cassie H; Zimmer-Gembeck, Melanie J; Farrell, Lara J; Webb, Haley

2014-09-01

Body dysmorphic disorder (BDD) is characterized by extreme preoccupation with perceived deficits in physical appearance, and sufferers experience severe impairment in functioning. Previous research has indicated that individuals with BDD are high in social anxiety, and often report being the victims of appearance-based teasing. However, there is little research into the possible mechanisms that might explain these relationships. The current study examined appearance-based rejection sensitivity as a mediator between perceived appearance-based victimization, social anxiety, and body dysmorphic symptoms in a sample of 237 Australian undergraduate psychology students. Appearance-based rejection sensitivity fully mediated the relationship between appearance-based victimization and body dysmorphic symptoms, and partially mediated the relationship between social anxiety and body dysmorphic symptoms. Findings suggest that individuals high in social anxiety or those who have a history of more appearance-based victimization may have a bias towards interpreting further appearance-based rejection, which may contribute to extreme appearance concerns such as BDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-Function Correlations using Scanning Laser Polarimetry in Primary Angle-Closure Glaucoma and Primary Open Angle Glaucoma

PubMed Central

Lee, Pei-Jung; Liu, Catherine Jui-Ling.; Wojciechowski, Robert; Bailey-Wilson, Joan E.; Cheng, Ching-Yu

2010-01-01

Purpose To assess the correlations between retinal nerve fiber layer (RNFL) thickness measured with scanning laser polarimetry (SLP) and visual field (VF) sensitivity in primary open angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Design Prospective, comparative, observational cases series Methods Fifty patients with POAG and 56 with PACG were examined using SLP with variable corneal compensation (GDx VCC) and Humphrey VF analyzer between August 2005 and July 2006 at Taipei Veterans General Hospital. Correlations between RNFL thickness and VF sensitivity, expressed as mean sensitivity (MS) in both decibel (dB) and 1/Lambert (L) scales, were estimated by Spearman's rank correlation coefficient (rs) and multivariate median regression models (pseudo R2). The correlations were determined globally and for six RNFL sectors and their corresponding VF regions. Results The correlation between RNFL thickness and MS (in dB) was weaker in the PACG group (rs = 0.38, P = 0.004, pseudo R2 = 0.17) than in the POAG group (rs = 0.51, P <0.001, pseudo R2 = 0.31), but the difference in the magnitude of correlation was not significant (P = 0.42).With Bonferroni correction, the structure-function correlation was significant in the superotemporal (rs = 0.62), superonasal (rs = 0.56), inferonasal (rs = 0.53), and inferotemporal (rs = 0.50) sectors in the POAG group (all P <0.001), while it was significant only in the superotemporal (rs = 0.53) and inferotemporal (rs = 0.48) sectors in the PACG group (both P <0.001). The results were similar when MS was expressed as 1/L scale. Conclusions Both POAG and PACG eyes had moderate structure-function correlations using SLP. Compared to eyes with POAG, fewer RNFL sectors have significant structure-function correlations in eyes with PACG. PMID:20202618

Validation of the Persian version of the Schizophrenia Cognition Rating Scale (SCoRS) in patients with schizophrenia.

PubMed

Mazhari, Shahrzad; Ghafaree-Nejad, Ali R; Soleymani-Zade, Somayeh; Keefe, Richard S E

2017-06-01

The Schizophrenia Cognition Rating Scale (SCoRS) is an interview-based assessment of cognition that involves interviews with patients and informants. The SCoRS has shown good reliability, validity, and sensitivity to cognitive impairment in schizophrenia, with the advantage of brief administration and scoring time. The present study aimed to test the concurrent validity of the Persian version of the SCoRS. A group of 35 patients with schizophrenia and a group of 35 healthy controls received the Persian-SCoRS in the first session, and a standardized performance-based cognitive battery, the Brief Assessment of Cognition in Schizophrenia (BACS), in the second session.Our results indicated that the Persian version of the SCoRS was sensitive to cognitive impairment in the patients. The Persian SCoRS global rating was significantly associated with the composite score generated from the Persian version of the BACS and predicted functional outcomes as measured by Global Assessment of Functioning (GAF) and World Health Organization Quality of Life (WHO QOL). A Persian version of the SCoRS, an interview based measure of cognition that included informants, is related to cognitive performance and global functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association.

PubMed

Souza, Manoel Carlos L A; Martins, Clarissa S; Silva-Junior, Ivan M; Chriguer, Rosangela S; Bueno, Ana C; Antonini, Sonir R; Silva, Wilson Araújo; Zago, Marco A; Moreira, Ayrton C; Castro, Margaret de

2014-02-01

The Brazilian population has heterogeneous ethnicity. No previous study evaluated NR3C1 polymorphisms in a Brazilian healthy population. We assessed NR3C1 polymorphisms in Brazilians of Caucasian, African and Asian ancestry (n = 380). In a subgroup (n = 40), we compared the genotypes to glucocorticoid (GC) sensitivity, which was previously evaluated by plasma (PF) and salivary (SF) cortisol after dexamethasone (DEX) suppression tests, GC receptor binding affinity (K d ), and DEX-50% inhibition (IC 50 ) of concanavalin-A-stimulated mononuclear cell proliferation. p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) allelic discrimination was performed by Real-Time PCR (Polymerase Chain Reaction). Exons 3 to 9 and exon/intron boundaries were amplified by PCR and sequenced. Genotypic frequencies (%) were: rs6195 (n = 380; AA:96.6/AG:3.14/GG:0.26), rs6189-6190 (n = 264; GG:99.6/GA:0.4), rs41423247 (n = 264; CC:57.9/CG:34.1/GG:8.0), rs6188 (n = 155; GG:69.6/GT:25.7/TT:4.7), rs258751 (n = 150; CC:88.0/CT:10.7/TT:1.3), rs6196 (n = 176; TT:77.2/TC:20.4/CC:2.4), rs67300719 (n = 137; CC:99.3/CT:0.7), and rs72542757 (n = 137; CC:99.3/CG:0.7). The rs67300719 and rs72542757 were found only in Asian descendants, in whom p.N363S and p.ER22/23EK were absent. The p.ER22/23EK was observed exclusively in Caucasian descendants. Hardy-Weinberg equilibrium was observed, except in the Asian for rs6188 and rs258751, and in the African for p.N363S. The K d , IC 50 , baseline and after DEX PF or SF did not differ between genotype groups. However, the mean DEX dose that suppressed PF or SF differed among the BclI genotypes (P = 0.03). DEX dose was higher in GG- (0.7 ± 0.2 mg) compared to GC- (0.47 ± 0.2 mg) and CC-carriers (0.47 ± 0.1 mg). The genotypic frequencies of NR3C1 polymorphisms in Brazilians are similar to worldwide populations. Additionally, the BclI polymorphism was associated with altered pituitary-adrenal axis GC sensitivity.

Decadal variability of surface incident solar radiation over China: Observations, satellite retrievals, and reanalyses

NASA Astrophysics Data System (ADS)

Wang, Kaicun; Ma, Qian; Li, Zhijun; Wang, Jiankai

2015-07-01

Existing studies have shown that observed surface incident solar radiation (Rs) over China may have important inhomogeneity issues. This study provides metadata and reference data to homogenize observed Rs, from which the decadal variability of Rs over China can be accurately derived. From 1958 to 1990, diffuse solar radiation (Rsdif) and direct solar radiation (Rsdir) were measured separately, and Rs was calculated as their sum. The pyranometers used to measure Rsdif had a strong sensitivity drift problem, which introduced a spurious decreasing trend into the observed Rsdif and Rs data, whereas the observed Rsdir did not suffer from this sensitivity drift problem. From 1990 to 1993, instruments and measurement methods were replaced and measuring stations were restructured in China, which introduced an abrupt increase in the observed Rs. Intercomparisons between observation-based and model-based Rs performed in this research show that sunshine duration (SunDu)-derived Rs is of high quality and can be used as reference data to homogenize observed Rs data. The homogenized and adjusted data of observed Rs combines the advantages of observed Rs in quantifying hourly to monthly variability and SunDu-derived Rs in depicting decadal variability and trend. Rs averaged over 105 stations in China decreased at -2.9 W m-2 per decade from 1961 to 1990 and remained stable afterward. This decadal variability is confirmed by the observed Rsdir and diurnal temperature ranges, and can be reproduced by high-quality Earth System Models. However, neither satellite retrievals nor reanalyses can accurately reproduce such decadal variability over China.

Association of Common Genetic Variants in the MAP4K4 Locus with Prediabetic Traits in Humans

PubMed Central

Ketterer, Caroline; Heni, Martin; Machicao, Fausto; Guilherme, Adilson; Grallert, Harald; Schulze, Matthias B.; Boeing, Heiner; Stefan, Norbert; Fritsche, Andreas; Czech, Michael P.; Häring, Hans-Ulrich

2012-01-01

Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is expressed in all diabetes-relevant tissues and mediates cytokine-induced insulin resistance. We investigated whether common single nucleotide polymorphisms (SNPs) in the MAP4K4 locus associate with glucose intolerance, insulin resistance, impaired insulin release, or elevated plasma cytokines. The best hit was tested for association with type 2 diabetes. Subjects (N = 1,769) were recruited from the Tübingen Family (TÜF) study for type 2 diabetes and genotyped for tagging SNPs. In a subgroup, cytokines were measured. Association with type 2 diabetes was tested in a prospective case-cohort study (N = 2,971) derived from the EPIC-Potsdam study. Three SNPs (rs6543087, rs17801985, rs1003376) revealed nominal and two SNPs (rs11674694, rs11678405) significant associations with 2-hour glucose levels. SNPs rs6543087 and rs11674694 were also nominally associated with decreased insulin sensitivity. Another two SNPs (rs2236936, rs2236935) showed associations with reduced insulin release, driven by effects in lean subjects only. Three SNPs (rs11674694, rs13003883, rs2236936) revealed nominal associations with IL-6 levels. SNP rs11674694 was significantly associated with type 2 diabetes. In conclusion, common variation in MAP4K4 is associated with insulin resistance and β-cell dysfunction, possibly via this gene’s role in inflammatory signalling. This variation’s impact on insulin sensitivity may be more important since its effect on insulin release vanishes with increasing BMI. PMID:23094072

Borderline Personality Features, Anger, and Intimate Partner Violence: An Experimental Manipulation of Rejection.

PubMed

Armenti, Nicholas A; Babcock, Julia C

2018-04-01

Individuals with borderline personality features may be susceptible to react to situational stressors with negative and interpersonally maladaptive emotionality (e.g., anger) and aggression. The current study attempted to test two moderated mediation models to investigate dispositional risk factors associated with borderline personality features and intimate partner violence (IPV). Results from an experimental rejection induction paradigm were examined using moderated regression to observe contextual reactions to imagined romantic rejection from a current romantic partner among individuals with borderline personality features. An ethnically diverse sample of 218 undergraduates at a large public university in the southwestern United States was recruited. Participants responded to demographic questions and self-report measures, and engaged in an experimental rejection induction paradigm. Borderline personality features was positively associated with rejection sensitivity, physical assault, and psychological aggression. Contrary to initial hypotheses, rejection sensitivity did not serve as a mediator of the relations between borderline personality features and physical assault and psychological aggression. However, trait anger mediated the relation between borderline personality features and psychological aggression. As such, trait anger may be an important explanatory variable in the relation between borderline personality features and psychological aggression specifically. Results of the rejection induction paradigm indicated that, for individuals who were asked to imagine an ambiguous rejection, the relation between borderline personality features and state anger post-rejection was strengthened. For individuals who imagined a critical rejection, there was no significant relation between borderline personality features and state anger post-rejection. Findings suggest that trait anger may be an important dispositional factor in the link between borderline personality features and IPV. In addition, contextual factors, such as ambiguous rejection by an intimate partner, may be especially relevant in activating anger or aggression in individuals with borderline personality features.

Prediction of heart transplant rejection with a breath test for markers of oxidative stress.

PubMed

Phillips, Michael; Boehmer, John P; Cataneo, Renee N; Cheema, Taseer; Eisen, Howard J; Fallon, John T; Fisher, Peter E; Gass, Alan; Greenberg, Joel; Kobashigawa, Jon; Mancini, Donna; Rayburn, Barry; Zucker, Mark J

2004-12-15

The Heart Allograft Rejection: Detection with Breath Alkanes in Low Levels study evaluated a breath test for oxidative stress in heart transplant recipients, and we report here a mathematical model predicting the probability of grade 3 rejection. The breath test divided the heart transplant recipients into 3 groups: positive for grade 3 rejection, negative for grade 3 rejection, and intermediate. The test was 100% sensitive for grade 3 heart transplant rejection when the p value was >/=0.98, and 100% specific when the p value was

The Child's Conception of Food: The Development of Food Rejections with Special Reference to Disgust and Contamination Sensitivity.

ERIC Educational Resources Information Center

Fallon, April E.; And Others

1984-01-01

Reports the results of structured interviews with mothers of 29 children three and one-half to 12 years of age, documenting the development of four categories of food rejection based on distaste, danger, disgust, and inappropriateness. Suggests that lack of contamination sensitivity in younger children is due to their belief that chemical…

Transplanting Sensitized Kidney Transplant Patients With Equivalent Outcomes Utilizing Stringent HLA Crossmatching.

PubMed

Rohan, Vinayak S; Taber, David J; Moussa, Omar; Pilch, Nicole A; Denmark, Signe; Meadows, Holly B; McGillicuddy, John W; Chavin, Kenneth D; Baliga, Prabhakar K; Bratton, Charles F

2017-02-01

Elevated panel reactive antibody levels have been traditionally associated with increased acute rejection rate and decreased long-term graft survival after kidney transplant. In this study, our objective was to determine patient and allograft outcomes in sensitized kidney transplant recipients with advanced HLA antibody detection and stringent protein sequence epitope analyses. This was a subanalysis of a prospective, risk-stratified randomized controlled trial that compared interleukin 2 receptor antagonist to rabbit antithymocyte globulin induction in 200 kidney transplant recipients, examining outcomes based on panel reactive antibody levels of < 20% (low) versus ≥ 20% (high, sensitized). The study was conducted between February 2009 and July 2011. All patients underwent solid-phase single antigen bead assays to detect HLA antibodies and stringent HLA epitope analyses with protein sequence alignment for virtual crossmatching. Delayed graft function, acute rejection rates, and graft loss were the main outcomes measured. Both the low (134 patients) and high (66 patients) panel reactive antibody level cohorts had equivalent induction and maintenance immunosuppression. Patients in the high-level group were more likely to be female (P < .001), African American (P < .001), and received a kidney from a deceased donor (P = .004). Acute rejection rates were similar between the low (rate of 8%) and high (rate of 9%) panel reactive antibody groups (P = .783). Delayed graft function, borderline rejection, graft loss, and death were not different between groups. Multivariate analyses demonstrated delayed graft function to be the strongest predictor of acute rejection (odds ratio, 5.7; P = .005); panel reactive antibody level, as a continuous variable, had no significant correlation with acute rejection (C statistic, 0.48; P = .771). Appropriate biologic matching with single antigen bead assays and stringent epitope analyses provided excellent outcomes in sensitized patients regardless of the induction therapy choice.

The CHRNA3 rs578776 Variant is Associated with an Intrinsic Reward Sensitivity Deficit in Smokers.

PubMed

Robinson, Jason D; Versace, Francesco; Lam, Cho Y; Minnix, Jennifer A; Engelmann, Jeffrey M; Cui, Yong; Karam-Hage, Maher; Shete, Sanjay S; Tomlinson, Gail E; Chen, Tina T-L; Wetter, David W; Green, Charles E; Cinciripini, Paul M

2013-01-01

A compromised brain reward system has been postulated as a key feature of drug dependence. We examined whether several polymorphisms of genes found to regulate nicotinic acetylcholine receptor (nAChR) and dopamine expression were related to an intrinsic reward sensitivity (IRS) deficit we previously identified among a subgroup of smokers using event-related potentials (ERPs). We examined genetic polymorphisms within the CHRNA5-A3-B4 gene cluster (CHRNA3 rs578776, CHRNA5 rs16969968, LOC123688 rs8034191, and CHRNA3 rs1051730), the ANKK1 gene (rs1800497), and the D2 dopamine receptor gene (DRD2 rs1079597, DRD2 rs1799732) from 104 smokers of European ancestry in a smoking cessation trial. Prior to treatment, we recorded ERPs evoked by emotional (both pleasant and unpleasant), neutral, and cigarette-related pictures. Smokers were assigned to two groups (IRS+/IRS-) based on the amplitude of the late positive potential (LPP) component to the pictures, a neural marker of motivational salience. Smokers (n = 42) with blunted brain responses to intrinsically rewarding (pleasant) pictures and enhanced responses to cigarette pictures were assigned to the IRS- group, while smokers (n = 62) with the opposite pattern of LPP responding were assigned to the IRS+ group. Carriers of the protective minor T allele (T/T, C/T) of the CHRNA3 rs578776 were less likely to be members of the IRS- group than those homozygous for the at-risk C allele (C/C). The CHRNA3 rs578776 polymorphism did not differ on questionnaires of nicotine dependence, depressed mood, or trait affective disposition and did not predict abstinence at 6 months after the quit date. These results suggest that polymorphisms of genes influencing nAChR expression are related to an endophenotype of reward sensitivity in smokers.

Top single nucleotide polymorphisms affecting carbohydrate metabolism in metabolic syndrome: from the LIPGENE study.

PubMed

Delgado-Lista, Javier; Perez-Martinez, Pablo; Solivera, Juan; Garcia-Rios, Antonio; Perez-Caballero, A I; Lovegrove, Julie A; Drevon, Christian A; Defoort, Catherine; Blaak, Ellen E; Dembinska-Kieć, Aldona; Risérus, Ulf; Herruzo-Gomez, Ezequiel; Camargo, Antonio; Ordovas, Jose M; Roche, Helen; Lopez-Miranda, José

2014-02-01

Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk. Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS. A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study. From 382 initial gene-phenotype associations between SNPs and any phenotypic variables, 61 (16% of the preselected variables) remained significant after bootstrapping. Top SNPs affecting glucose metabolism variables were as follows: fasting glucose, rs26125 (PPARGC1B); fasting insulin, rs4759277 (LRP1); C-peptide, rs4759277 (LRP1); homeostasis assessment of insulin resistance, rs4759277 (LRP1); quantitative insulin sensitivity check index, rs184003 (AGER); sensitivity index, rs7301876 (ABCC9), acute insulin response to glucose, rs290481 (TCF7L2); and disposition index, rs12691 (CEBPA). We describe here the top SNPs linked to phenotypic features in carbohydrate metabolism among approximately 1000 candidate gene variations in fasting and postprandial samples of 450 patients with MetS from the LIPGENE study.

Parallel Analysis of 124 Universal SNPs for Human Identification by Targeted Semiconductor Sequencing

PubMed Central

Zhang, Suhua; Bian, Yingnan; Zhang, Zheren; Zheng, Hancheng; Wang, Zheng; Zha, Lagabaiyila; Cai, Jifeng; Gao, Yuzhen; Ji, Chaoneng; Hou, Yiping; Li, Chengtao

2015-01-01

SNPs, abundant in human genome with lower mutation rate, are attractive to genetic application like forensic, anthropological and evolutionary studies. Universal SNPs showing little allelic frequency variation among populations while remaining highly informative for human identification were obtained from previous studies. However, genotyping tools target only dozens of markers simultaneously, limiting their applications. Here, 124 SNPs were simultaneous tested using Ampliseq technology with Ion Torrent PGM platform. Concordance study was performed with 2 reference samples of 9947A and 9948 between NGS and Sanger sequencing. Full concordance were obtained except genotype of rs576261 with 9947A. Parameter of FMAR (%) was introduced for NGS data analysis for the first time, evaluating allelic performance, sensitivity testing and mixture testing. FMAR values for accurate heterozygotes should be range from 50% to 60%, for homozygotes or Y-SNP should be above 90%. SNPs of rs7520386, rs4530059, rs214955, rs1523537, rs2342747, rs576261 and rs12997453 were recognized as poorly performing loci, either with allelic imbalance or with lower coverage. Sensitivity testing demonstrated that with DNA range from 10 ng-0.5 ng, all correct genotypes were obtained. For mixture testing, a clear linear correlation (R2 = 0.9429) between the excepted FMAR and observed FMAR values of mixtures was observed. PMID:26691610

Effectiveness of rapid prescreening and 10% rescreening in liquid-based Papanicolaou testing.

PubMed

Currens, Heather S; Nejkauf, Katharine; Wagner, Lynn; Raab, Stephen S

2012-01-01

Although rapid prescreening (RPS) has been shown to be an effective quality control procedure for detecting false-negative conventional Papanicolaou (Pap) tests, RPS has not been widely implemented in the United States. In our laboratory, cytotechnologists performed RPS in 3,567 liquid-based Pap tests: 1,911 SurePath (BD Diagnostics-TriPath, Burlington, NC) preparations that were manually screened and 1,656 ThinPrep Pap tests (Hologic, Bedford, MA) that were imaged using the ThinPrep Imaging System (Hologic). We compared the sensitivity of RPS, 10% rescreening (R-10%), and routine screening (RS). In contrast with previously published findings, we found that RS + RPS did not improve screening sensitivity compared with RS + R-10%. These results support the following hypotheses: (1) Higher baseline RS sensitivity as a result of Pap test diagnoses standardization implemented for quality improvement purposes decreases the performance impact of RPS. (2) R-10% and RPS quality assurance methods detect diagnostic failures caused by different types of cognitive errors.

Mad Cow Disease and U.S. Beef Trade

DTIC Science & Technology

2006-12-06

1 For additional details and background see CRS Report RS22345, BSE (“Mad Cow Disease:): A Brief Overview, and CRS Report RL32199, Bovine Spongiform ...foreign markets that banned U.S. beef when a cow in Washington state tested positive for bovine spongiform encephalopathy (BSE, or mad cow disease) in...rejection of three shipments of U.S. beef because of the presence of bone fragments. CRS-4 8 See also CRS Report RL32932, Bovine Spongiform

Decoy receptors block TRAIL sensitivity at a supracellular level: the role of stromal cells in controlling tumour TRAIL sensitivity.

PubMed

O'Leary, L; van der Sloot, A M; Reis, C R; Deegan, S; Ryan, A E; Dhami, S P S; Murillo, L S; Cool, R H; Correa de Sampaio, P; Thompson, K; Murphy, G; Quax, W J; Serrano, L; Samali, A; Szegezdi, E

2016-03-10

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand cytokine known for its cytotoxic activity against malignantly transformed cells. TRAIL induces cell death through binding to death receptors DR4 and DR5. The inhibitory decoy receptors (DcR1 and DcR2) co-expressed with death receptor 4 (DR4)/DR5 on the same cell can block the transmission of the apoptotic signal. Here, we show that DcRs also regulate TRAIL sensitivity at a supracellular level and thus represent a mechanism by which the microenvironment can diminish tumour TRAIL sensitivity. Mathematical modelling and layered or spheroid stroma-extracellular matrix-tumour cultures were used to model the tumour microenvironment. By engineering TRAIL to escape binding by DcRs, we found that DcRs do not only act in a cell-autonomous or cis-regulatory manner, but also exert trans-cellular regulation originating from stromal cells and affect tumour cells, highlighting the potent inhibitory effect of DcRs in the tumour tissue and the necessity of selective targeting of the two death-inducing TRAIL receptors to maximise efficacy.

Landscape position influences soil respiration variability and sensitivity to physiological drivers in mixed-use lands of Southern California, USA

NASA Astrophysics Data System (ADS)

Crum, Steven M.; Liang, Liyin L.; Jenerette, G. Darrel

2016-10-01

Linking variation in ecosystem functioning to physiological and landscape drivers has become an important research need for understanding ecosystem responses to global changes. We investigate how these contrasting scale-dependent ecosystem drivers influence soil respiration (Rs), a key ecosystem process, using in situ landscape surveys and experimental subsidies of water and labile carbon. Surveys and experiments were conducted in summer and winter seasons and were distributed along a coastal to desert climate gradient and among the dominant land use classes in Southern California, USA. We found that Rs decreased from lawn to agricultural and wildland land uses for both seasons and along the climate gradient in the summer while increasing along the climate gradient in the winter. Rs variation was positively correlated with soil temperature and negatively to soil moisture and substrate. Water additions increased Rs in wildland land uses, while urban land uses responded little or negatively. However, most land uses exhibited carbon limitation, with wildlands experiencing largest responses to labile carbon additions. These findings show that intensively managed land uses have increased rates, decreased spatial variation, and decreased sensitivity to environmental conditions in Rs compared to wildlands, while increasing aridity has the opposite effect. In linking scales, physiological drivers were correlated with Rs but landscape position influenced Rs by altering both the physiological drivers and the sensitivity to the drivers. Systematic evaluation of physiological and landscape variation provides a framework for understanding the effects of interactive global change drivers to ecosystem metabolism across multiple scales.

Regularised extreme learning machine with misclassification cost and rejection cost for gene expression data classification.

PubMed

Lu, Huijuan; Wei, Shasha; Zhou, Zili; Miao, Yanzi; Lu, Yi

2015-01-01

The main purpose of traditional classification algorithms on bioinformatics application is to acquire better classification accuracy. However, these algorithms cannot meet the requirement that minimises the average misclassification cost. In this paper, a new algorithm of cost-sensitive regularised extreme learning machine (CS-RELM) was proposed by using probability estimation and misclassification cost to reconstruct the classification results. By improving the classification accuracy of a group of small sample which higher misclassification cost, the new CS-RELM can minimise the classification cost. The 'rejection cost' was integrated into CS-RELM algorithm to further reduce the average misclassification cost. By using Colon Tumour dataset and SRBCT (Small Round Blue Cells Tumour) dataset, CS-RELM was compared with other cost-sensitive algorithms such as extreme learning machine (ELM), cost-sensitive extreme learning machine, regularised extreme learning machine, cost-sensitive support vector machine (SVM). The results of experiments show that CS-RELM with embedded rejection cost could reduce the average cost of misclassification and made more credible classification decision than others.

T1 Mapping by Cardiac Magnetic Resonance and Multidimensional Speckle-Tracking Strain by Echocardiography for the Detection of Acute Cellular Rejection in Cardiac Allograft Recipients.

PubMed

Sade, Leyla Elif; Hazirolan, Tuncay; Kozan, Hatice; Ozdemir, Handan; Hayran, Mutlu; Eroglu, Serpil; Pirat, Bahar; Sezgin, Atilla; Muderrisoglu, Haldun

2018-04-14

The aim of this study was to test the hypothesis that echocardiographic strain imaging, by tracking subtle alterations in myocardial function, and cardiac magnetic resonance T1 mapping, by quantifying tissue properties, are useful and complement each other to detect acute cellular rejection in heart transplant recipients. Noninvasive alternatives to endomyocardial biopsy are highly desirable to monitor acute cellular rejection. Surveillance endomyocardial biopsies, catheterizations, and echocardiograms performed serially according to institutional protocol since transplantation were retrospectively reviewed. Sixteen-segment global longitudinal strain (GLS) and circumferential strain were measured before, during, and after the first rejection and at 2 time points for patients without rejection using Velocity Vector Imaging for the first part of the study. The second part, with cardiac magnetic resonance added to the protocol, served to validate previously derived strain cutoffs, examine the progression of strain over time, and to determine the accuracy of strain and T1 measurements to define acute cellular rejection. All tests were performed within 48 h. Median time to first rejection (16 grade 1 rejection, 15 grade ≥2 rejection) was 3 months (interquartile range: 3 to 36 months) in 49 patients. GLS and global circumferential strain worsened significantly during grade 1 rejection and ≥2 rejection and were independent predictors of any rejection. In the second part of the study, T1 time ≥1,090 ms, extracellular volume ≥32%, GLS >-14%, and global circumferential strain ≥-24% had 100% sensitivity and 100% negative predictive value to define grade ≥2 rejection with 70%, 63%, 55%, and 35% positive predictive values, respectively. The combination of GLS >-16% and T1 time ≥1,060 ms defined grade 1 rejection with 91% sensitivity and 92% negative predictive value. After successful treatment, T1 times decreased significantly. T1 mapping and echocardiographic GLS can serve to guide endomyocardial biopsy selectively. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody Mediated Rejection After Vascularized Composite Allotransplantation

DTIC Science & Technology

2017-10-01

Award Number: W81XWH-16-1-0664 TITLE: Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody-Mediated Rejection after...Annual 3. DATES COVERED 15 Sep 2016 – 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Autologous Hematopoietic Stem Cell Transplantation to...sensitization, autologous hematopoietic stem cell transplantation, antibody mediated rejection, donor specific antibodies 16. SECURITY CLASSIFICATION OF

Fisher Consistency of AM-Estimates of the Autoregression Parameter Using Hard Rejection Filter Cleaners

DTIC Science & Technology

1987-02-04

U5tr,)! P(U 5-t Since U - F with F RS, we get (3.1). Case b: 0 S 5 k -a Now P([U~t]riM) = P(UZk-a) and P([ Ugt ]rM) = P(US-k-a) S P(US-(k-a)) which again...robustness for autoregressive processes." The Annals of Statistics, 12, 843-863. Mallows, C.L. (1980). "Some theory of nonlinear smoothen." The Annals of

Polarization in Raman spectroscopy helps explain bone brittleness in genetic mouse models

NASA Astrophysics Data System (ADS)

Makowski, Alexander J.; Pence, Isaac J.; Uppuganti, Sasidhar; Zein-Sabatto, Ahbid; Huszagh, Meredith C.; Mahadevan-Jansen, Anita; Nyman, Jeffry S.

2014-11-01

Raman spectroscopy (RS) has been extensively used to characterize bone composition. However, the link between bone biomechanics and RS measures is not well established. Here, we leveraged the sensitivity of RS polarization to organization, thereby assessing whether RS can explain differences in bone toughness in genetic mouse models for which traditional RS peak ratios are not informative. In the selected mutant mice-activating transcription factor 4 (ATF4) or matrix metalloproteinase 9 (MMP9) knock-outs-toughness is reduced but differences in bone strength do not exist between knock-out and corresponding wild-type controls. To incorporate differences in the RS of bone occurring at peak shoulders, a multivariate approach was used. Full spectrum principal components analysis of two paired, orthogonal bone orientations (relative to laser polarization) improved genotype classification and correlation to bone toughness when compared to traditional peak ratios. When applied to femurs from wild-type mice at 8 and 20 weeks of age, the principal components of orthogonal bone orientations improved age classification but not the explanation of the maturation-related increase in strength. Overall, increasing polarization information by collecting spectra from two bone orientations improves the ability of multivariate RS to explain variance in bone toughness, likely due to polarization sensitivity to organizational changes in both mineral and collagen.

Pulp Sensitivity: Influence of Sex, Psychosocial Variables, COMT Gene, and Chronic Facial Pain.

PubMed

Mladenovic, Irena; Krunic, Jelena; Supic, Gordana; Kozomara, Ruzica; Bokonjic, Dejan; Stojanovic, Nikola; Magic, Zvonko

2018-05-01

The purpose of this study was to evaluate the associations of variability in pulp sensitivity with sex, psychosocial variables, the gene that encodes for the enzyme catechol-O-methyltransferase (COMT), and chronic painful conditions (temporomandibular disorders [TMDs]). The study was composed of 97 subjects (68 women and 29 men aged 20-44 years). The electric (electric pulp tester) and cold (refrigerant spray) stimuli were performed on mandibular lateral incisors. The results were expressed as pain threshold values for electric pulp stimulation (0-80 units) and as pain intensity scores (visual numeric scale from 0-10) for cold stimulation. The Research Diagnostic Criteria for TMD were used to assess TMD, depression, and somatization. DNA extracted from peripheral blood was genotyped for 3 COMT polymorphisms (rs4680, rs6269, and rs165774) using the real-time TaqMan method. Multivariate linear regression was used to investigate the joint effect of the predictor variables (clinical and genetic) on pulp sensitivity (dependent variables). Threshold responses to electric stimuli were related to female sex (P < .01) and the homozygous GG genotype for the rs165774 polymorphism (P < .05). Pain intensity to cold stimuli was higher in TMD patients (P < .01) and tended to be higher in women. Multivariate linear regression identified sex and the rs165774 COMT polymorphism as the determinants of electric pain sensitivity, whereas TMD accounts for the variability in the cold response. Our findings indicate that sex/a COMT gene variant and TMD as a chronic painful condition may contribute to individual variation in electric and cold pulp sensitivity, respectively. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Advances in tumor diagnosis using OCT and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Zakharov, V. P.; Bratchenko, I. A.; Kozlov, S. V.; Moryatov, A. A.; Kornilin, D. V.; Myakinin, O. O.; Artemyev, D. N.

2014-05-01

Complex investigation of malignant tumors was performed with combined optical coherence tomography (OCT) and Raman spectroscopy (RS) setup: 22 ex vivo lung tissue samples and 23 in vivo experiments with skin tumors. It was shown that combined RS-OCT unit may be used for precise tissue morphology visualization with simultaneous tumor type determination (BCC, malignant melanoma of skin tissues, adenocarcinoma and squamous cell carcinoma of lung). Fast RS phase method for skin and lung tumors identification was proposed. It is based on alteration of Raman spectral intensity in 1300-1340, 1440-1460 and 1640-1680 cm-1 bands for healthy and malignant tissue. Complex method could identify: malignant melanoma with 88.9% sensitivity and 87.8% specificity; adenocarcinoma with 100% sensitivity and 81.5% specificity; squamous cell carcinomas with 90.9% sensitivity and 77.8% specificity.

Polymorphisms of the oxytocin receptor gene and overeating: the intermediary role of endophenotypic risk factors

PubMed Central

Davis, C; Patte, K; Zai, C; Kennedy, J L

2017-01-01

Background/Objectives: Oxytocin (OXT) is an evolutionarily ancient neuropeptide with strong links to affiliative and prosocial behaviors, and the management of stress. Increases in OXT also tend to decrease food intake, especially of sweet carbohydrates. The social correlates of low OXT levels mesh with the social deficits and stress proneness identified in interpersonal models of overeating, as well as the increased appetite for highly palatable foods typically seen in chronic overeaters. The objectives of this study were to investigate links between polymorphisms of the oxytocin receptor (OXTR) gene and overeating, and to examine OXTR links with relevant endophenotypes of overeating related to reward and stress sensitivity, and to food preferences. Subject/Methods: The sample comprised 460 adults between the ages of 25 and 50 years recruited from the community, and representing a broad range of body weights. Overeating, reward and punishment sensitivity, and food preferences, were quantified as composite variables using well-validated questionnaires. In addition, seven single-nucleotide polymorphisms (rs237878, rs237885, rs2268493, rs2268494, rs2254298, rs53576, rs2268498) of the OXTR gene were genotyped. Results: Analyses identified a four-marker haplotype that was significantly related to food preferences. Individual genotype analyses also found that at least one of the markers was related to each of the phenotypic variables. In addition, an empirically derived structural equation model linking genetic and phenotype variables produced a good fit to the data. Conclusions: The results of this preliminary study have demonstrated that OXTR variation is associated with overeating, and with endophenotypic traits such as sweet and fatty food preferences, and reward and punishment sensitivity. In general, the genetic findings also favor the view that overeating may be associated with relatively low basal OXT levels. PMID:28530679

Polymorphisms of the oxytocin receptor gene and overeating: the intermediary role of endophenotypic risk factors.

PubMed

Davis, C; Patte, K; Zai, C; Kennedy, J L

2017-05-22

Oxytocin (OXT) is an evolutionarily ancient neuropeptide with strong links to affiliative and prosocial behaviors, and the management of stress. Increases in OXT also tend to decrease food intake, especially of sweet carbohydrates. The social correlates of low OXT levels mesh with the social deficits and stress proneness identified in interpersonal models of overeating, as well as the increased appetite for highly palatable foods typically seen in chronic overeaters. The objectives of this study were to investigate links between polymorphisms of the oxytocin receptor (OXTR) gene and overeating, and to examine OXTR links with relevant endophenotypes of overeating related to reward and stress sensitivity, and to food preferences. The sample comprised 460 adults between the ages of 25 and 50 years recruited from the community, and representing a broad range of body weights. Overeating, reward and punishment sensitivity, and food preferences, were quantified as composite variables using well-validated questionnaires. In addition, seven single-nucleotide polymorphisms (rs237878, rs237885, rs2268493, rs2268494, rs2254298, rs53576, rs2268498) of the OXTR gene were genotyped. Analyses identified a four-marker haplotype that was significantly related to food preferences. Individual genotype analyses also found that at least one of the markers was related to each of the phenotypic variables. In addition, an empirically derived structural equation model linking genetic and phenotype variables produced a good fit to the data. The results of this preliminary study have demonstrated that OXTR variation is associated with overeating, and with endophenotypic traits such as sweet and fatty food preferences, and reward and punishment sensitivity. In general, the genetic findings also favor the view that overeating may be associated with relatively low basal OXT levels.

Predictive parameters for return to pre-injury level of sport 6 months following anterior cruciate ligament reconstruction surgery.

PubMed

Müller, Ulrike; Krüger-Franke, Michael; Schmidt, Michael; Rosemeyer, Bernd

2015-12-01

The aim of the study was to find predictive parameters for a successful resumption of pre-injury level of sport 6 months post anterior cruciate ligament (ACL) reconstruction. In a prospective study, 40 patients with a ruptured ACL were surgically treated with semitendinosus tendon autograft. Six months after surgery, strength of knee extensors and flexors, four single-leg hop tests, Anterior Cruciate Ligament-Return to Sport after Injury Scale (ACL-RSI), subjective International Knee Documentation Committee (IKDC) 2000 and the Tampa Scale of Kinesiophobia-11 (TSK-11) were assessed. Seven months post-operatively, a standardized interview was conducted to identify "return to sport" (RS) and "non-return to sport" (nRS) patients. Logistic regression and "Receiver Operating Characteristic" (ROC) analyses were used to determine predictive parameters. No significant differences could be detected between RS and nRS patients concerning socio-demographic data, muscle tests, square hop and TSK-11. In nRS patients, the Limb Symmetry Index (LSI) of single hop for distance (p = 0.005), crossover hop (p = 0.008) and triple hop (p = 0.001) were significantly lower, in addition to the ACL-RSI (p = 0.013) and IKDC 2000 (p = 0.037). The cut-off points for LSI single hop for distance were 75.4 % (sensitivity 0.74; specificity 0.88), and for ACL-RSI 51.3 points (sensitivity 0.97; specificity 0.63). Logistic regression distinguished between RS and nRS subjects (sensitivity 0.97; specificity 0.63). The single hop for distance and ACL-RSI were found to be the strongest predictive parameters, assessing both the objective functional and the subjective psychological aspects of returning to sport. Both tests may help to identify patients at risk of not returning to pre-injury sport. II.

Structural properties and in vitro digestibility of edible and pH-sensitive films made from guinea arrowroot starch and wastes from wine manufacture.

PubMed

Gutiérrez, Tomy J; Herniou-Julien, Clémence; Álvarez, Kelvia; Alvarez, Vera A

2018-03-15

A non-conventional starch obtained from guinea arrowroot tubers (Calathea allouia) grown in the Amazon was used as a polymeric matrix for the development of edible films. The films were manufactured by blending/thermo molding and plasticized with glycerol. Agro-industrial wastes from wine manufacture (grape waste flour and grape waste extract) were used as natural fillers of the thermoplastic starch (TPS) matrices. The results showed that the natural fillers caused cross-linking in the TPS matrix. This led to the production of films with higher resistant starch (RS) content, especially RS type 4 (RS4), although the DSC results showed that the films developed also contained RS type 3 (RS3). As expected, the presence of RS reduced the in vitro digestibility rate. Films made with the natural fillers were also less hydrophilic, had a greater thermal resistance, and tended towards ductile mechanical behavior. Finally, the edible film containing grape waste flour as a natural filler proved to be pH-sensitive, although this material disintegrated under alkaline conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

HLA class I antibodies trigger increased adherence of monocytes to endothelial cells by eliciting an increase in endothelial P-selectin and, depending on subclass, by engaging FcγRs1

PubMed Central

Valenzuela, Nicole M; Mulder, Arend; Reed, Elaine F

2013-01-01

Antibody-mediated rejection of solid organ transplants is characterized by intragraft macrophages. It is incompletely understood how donor specific antibody binding to graft endothelium promotes monocyte adhesion, and what, if any, contribution is made by the Fc region of the antibody. We investigated the mechanisms underlying monocyte recruitment by HLA class I antibody-activated endothelium. We used a panel of murine monoclonal antibodies of different subclasses to crosslink HLA I on human aortic, venous and microvascular endothelial cells, and measured the binding of human monocytic cell lines and peripheral blood monocytes. Both anti-HLA I murine IgG1 and mIgG2a induced endothelial P-selectin, which was required for monocyte adhesion to endothelium irrespective of subclass. Mouse IgG2a but not mIgG1 could bind human FcγRs. Accordingly, HLA I mIgG2a but not mIgG1 treatment of endothelial cells significantly augmented recruitment, predominantly through FcγRI, and, to a lesser extent, FcγRIIa. Moreover, HLA I mIgG2a promoted firm adhesion of monocytes to ICAM-1 through Mac-1, which may explain the prominence of monocytes during antibody mediated rejection. We confirmed these observations using human HLA allele specific monoclonal antibodies and IgG purified from transplant patient sera. HLA I antibodies universally elicit endothelial exocytosis leading to monocyte adherence, implying that P-selectin is a putative therapeutic target to prevent macrophage infiltration during antibody-mediated rejection. Importantly, the subclass of donor specific antibody may influence its pathogenesis. These results imply that hIgG1 and hIgG3 should have a greater capacity to trigger monocyte infiltration into the graft than IgG2 or IgG4 due to enhancement by FcγR interactions. PMID:23690477

Influence of promoter/enhancer region haplotypes on MGMT transcriptional regulation: a potential biomarker for human sensitivity to alkylating agents.

PubMed

Xu, Meixiang; Nekhayeva, Ilona; Cross, Courtney E; Rondelli, Catherine M; Wickliffe, Jeffrey K; Abdel-Rahman, Sherif Z

2014-03-01

The O6-methylguanine-DNA methyltransferase gene (MGMT) encodes the direct reversal DNA repair protein that removes alkyl adducts from the O6 position of guanine. Several single-nucleotide polymorphisms (SNPs) exist in the MGMT promoter/enhancer (P/E) region. However, the haplotype structure encompassing these SNPs and their functional/biological significance are currently unknown. We hypothesized that MGMT P/E haplotypes, rather than individual SNPs, alter MGMT transcription and can thus alter human sensitivity to alkylating agents. To identify the haplotype structure encompassing the MGMT P/E region SNPs, we sequenced 104 DNA samples from healthy individuals and inferred the haplotypes using the data generated. We identified eight SNPs in this region, namely T7C (rs180989103), T135G (rs1711646), G290A (rs61859810), C485A (rs1625649), C575A (rs113813075), G666A (rs34180180), C777A (rs34138162) and C1099T (rs16906252). Phylogenetics and Sequence Evolution analysis predicted 21 potential haplotypes that encompass these SNPs ranging in frequencies from 0.000048 to 0.39. Of these, 10 were identified in our study population as 20 paired haplotype combinations. To determine the functional significance of these haplotypes, luciferase reporter constructs representing these haplotypes were transfected into glioblastoma cells and their effect on MGMT promoter activity was determined. Compared with the most common (reference) haplotype 1, seven haplotypes significantly upregulated MGMT promoter activity (18-119% increase; P < 0.05), six significantly downregulated MGMT promoter activity (29-97% decrease; P < 0.05) and one haplotype had no effect. Mechanistic studies conducted support the conclusion that MGMT P/E haplotypes, rather than individual SNPs, differentially regulate MGMT transcription and could thus play a significant role in human sensitivity to environmental and therapeutic alkylating agents.

Defensive Physiological Reactions to Rejection

PubMed Central

Gyurak, Anett; Ayduk, Özlem

2014-01-01

We examined the hypothesis that rejection automatically elicits defensive physiological reactions in people with low self-esteem (SE) but that attentional control moderates this effect. Undergraduates (N = 67) completed questionnaire measures of SE and attentional control. Their eye-blink responses to startle probes were measured while they viewed paintings related to rejection and acceptance themes. The stimuli also included positive-, negative-, and neutral-valence control paintings unrelated to rejection. As predicted, compared with people high in SE, those low in SE showed stronger startle eye-blink responses to paintings related to rejection, but not to negative paintings. Paintings related to acceptance did not attenuate their physiological reactivity. Furthermore, attentional control moderated their sensitivity to rejection, such that low SE was related to greater eye-blink responses to rejection only among individuals who were low in attentional control. Implications of the role of attentional control as a top-down process regulating emotional reactivity in people with low SE are discussed. PMID:17894606

Frequency-dependent glycinergic inhibition modulates plasticity in hippocampus.

PubMed

Keck, Tara; Lillis, Kyle P; Zhou, Yu-Dong; White, John A

2008-07-16

Previous studies have demonstrated the presence of functional glycine receptors (GlyRs) in hippocampus. In this work, we examine the baseline activity and activity-dependent modulation of GlyRs in region CA1. We find that strychnine-sensitive GlyRs are open in the resting CA1 pyramidal cell, creating a state of tonic inhibition that "shunts" the magnitude of EPSPs evoked by electrical stimulation of the Schaffer collateral inputs. This GlyR-mediated shunting conductance is independent of the presynaptic stimulation rate; however, pairs of presynaptic and postsynaptic action potentials, repeated at frequencies above 5 Hz, reduce the GlyR-mediated conductance and increase peak EPSP magnitudes to levels at least 20% larger than those seen with presynaptic stimulation alone. We refer to this phenomenon as rate-dependent efficacy (RDE). Exogenous GlyR agonists (glycine, taurine) block RDE by preventing the closure of postsynaptic GlyRs. The GlyR antagonist strychnine blocks postsynaptic GlyRs under all conditions, occluding RDE. During RDE, GlyRs are less responsive to local glycine application, suggesting that a reduction in the number or sensitivity of membrane-inserted GlyRs underlies RDE. By extending the RDE induction protocol to include 500 paired presynaptic and postsynaptic spikes, we can induce long-term synaptic depression (LTD). Manipulations that lead to reduced functionality of GlyRs, either pharmacologically or through RDE, also lead to increased LTD. This result suggests that RDE contributes to long-term synaptic plasticity in the hippocampus.

Polarized release of hepatic microRNAs into bile and serum in response to cellular injury and impaired liver function.

PubMed

Verhoeven, Cornelia J; Farid, Waqar R R; Roest, Henk P; Ramakrishnaiah, Vedashree; de Ruiter, Petra E; de Jonge, Jeroen; Kwekkeboom, Jaap; Metselaar, Herold J; Tilanus, Hugo W; Kazemier, Geert; Ijzermans, Jan N M; van der Laan, Luc J W

2016-06-01

Extracellular microRNAs (miRNAs) in serum and bile are currently under intense investigation for biomarker purposes in liver disease. However, the directions and pathways by which miRNAs are released from hepatic cells remains largely unknown. Here, we investigated the release of hepatocyte and cholangiocyte-derived miRNAs (HDmiRs and CDmiRs) into blood and bile during various (patho)physiological hepatic conditions. MiRNA release was analysed using longitudinally collected tissue and paired bile and serum samples (n = 124) that were obtained from liver transplant recipients during follow-up. Cell-type specificity of HDmiRs and CDmiRs was confirmed in liver and common bile duct biopsies (P < 0.001). Analysis of paired bile and serum samples showed up to 20-times higher miRNA-levels in bile compared to serum (P < 0.0001). Fractionation of bile showed the majority of miRNAs being present in the unpelletable supernatant, where protein conjunctions protect miRNAs against degradation (P < 0.0001). During episodes of liver injury and histologically proven rejection in liver transplant recipients, relative HDmiR-levels in bile decreased while its levels in serum increased (P ≤ 0.015). Simultaneously, relative CDmiR-levels in bile significantly increased, while their levels in serum decreased. Related to liver excretory function, a strong positive correlation was observed between HDmiR-122 levels and bilirubin excretion into bile (R = 0.694, P < 0.0001), whereas CDmiRs showed an inverse correlation (P < 0.05). During impaired excretory function and injury, the liver shows polarized release of extracellular HDmiRs and CDmiRs. This sheds new light on the biology of hepatic miRNA release which is relevant for the interpretation of hepatic miRNAs as biomarkers. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Decadal variability of surface solar radiation over China

NASA Astrophysics Data System (ADS)

Wang, K.

2015-12-01

Observations show that national average surface solar radiation (Rs) decreased by -8.0 W m-2 per decade from 1960 to 1990 and sharply increased from 1990 to 1993. However, none of the state-of-the-art climate models can reproduce such decrease/increase of Rs. This study shows that Rs observations over China have significant inhomogeneity. Before 1989, Rs was calculated as a sum of direct (Rsdir) and diffuse (Rsdif) solar radiation observations measured by pyrheliometers and shaded pyranometers separately. Due to technical limitations and irregular calibration, pyranometers before 1990 had a strong sensitivity drift problem, which introduced crucial spurious decreasing trends into Rsdif and Rs data. From 1990 to 1993, instruments and measurement methods were replaced and measuring stations were restructured in China, which resulted in an abrupt increase in the observed Rs. Rs calculated from Sunshine duration (SunDu) provide a reliable reference in assessing decadal variability of Rs. SunDu derived Rs have no sensitivity drift problem because of its daily changed recording material. SunDu-derived Rs averaged over China decreased by -2.9 W m-2 per decade from 1961 to 1990, and had a negligible trend afterward. During the period of 1994-2012 when Rs observations were free of inhomogeneity mentioned above, the observed and SunDu-derived Rs consistently show a negligible trend, being less than 0.1 W m-2 per decade. These trends can be reproduced by high-quality CMIP5 Earth System Models (ESM). This level of agreement is due to the incorporation of a near real emission inventory of atmospheric aerosols by CMIP5 ESMs. Rs from ERA-Interim has a good agreement with SunDu-derived Rs. However, ERA-interim does not allow aerosol loading to change annually. ERA-Interim Rs shows an unreliable increasing trend of 1.9 W m-2 per decade from 1990 to 2013 because it does not include the impact of recent increased atmospheric aerosols over China. GEWEX Rs calculated from ISCCP cloud products show a significant but erratic decreasing trend of -3.1 W m-2 per decade from 1983 to 2007 over China. The ISCCP cloud products aggregate cloud observations from polar orbit and geostationary satellites directly, which introduced to inhomogeneity to ISCCP cloud and GEWEX Rs products.

Dietary resistant starch dose-dependently reduces adiposity in obesity-prone and obesity-resistant male rats.

PubMed

Belobrajdic, Damien P; King, Roger A; Christophersen, Claus T; Bird, Anthony R

2012-10-25

Animal studies show that diets containing resistant starch (RS) at levels not achievable in the human diet result in lower body weight and/or adiposity in rodents. We aimed to determine whether RS dose-dependently reduces adiposity in obesity-prone (OP) and obesity-resistant (OR) rats. Male Sprague-Dawley rats (n=120) were fed a moderate-fat, high-energy diet for 4 wk. Rats that gained the most weight (40%) were classified as obesity-prone (OP) and obesity-resistant (OR) rats were the 40% that gained the least weight. OP and OR rats were randomly allocated to one of six groups (n=8 for each phenotype). One group was killed for baseline measurements, the other five groups were allocated to AIN-93 based diets that contained 0, 4, 8, 12 and 16% RS (as high amylose maize starch) for 4 wk. These diets were matched for total carbohydrate content. At 0, 4 and 7 wk from the start of the study insulin sensitivity was calculated by homeostasis model assessment of insulin resistance (HOMA-IR) and adiposity was determined by dual-energy X-ray absorptiometry (DXA). At 8 wk, rats were euthanized and fat pad weights, intestinal digesta short chain fatty acid (SCFA) pools and plasma gut hormone levels were determined. Obesity prone rats gained less weight with 4, 12 and 16% RS compared to 0% RS, but the effect in OR animals was significant only at 16% RS. Irrespective of phenotype, diets containing ≥8% RS reduced adiposity compared to 0% RS. Energy intake decreased by 9.8 kJ/d for every 4% increase in RS. All diets containing RS increased total SCFA pools in the caecum and lowered plasma GIP concentrations compared to the 0% RS, whereas plasma GLP-1 and PYY were increased when the diet contained at least 8% RS. Insulin sensitivity was not affected by RS. RS in amounts that could be potentially consumed by humans were effective in reducing adiposity and weight gain in OP and OR rats, due in part to a reduction in energy intake, and changes in gut hormones and large bowel carbohydrate fermentation.

A gene variation (rs12691) in the CCAT/enhancer binding protein α modulates glucose metabolism in metabolic syndrome.

PubMed

Delgado-Lista, J; Perez-Martinez, P; Garcia-Rios, A; Phillips, C M; Hall, W; Gjelstad, I M F; Lairon, D; Saris, W; Kieć-Wilk, B; Karlström, B; Drevon, C A; Defoort, C; Blaak, E E; Dembinska-Kieć, A; Risérus, U; Lovegrove, J A; Roche, H M; Lopez-Miranda, J

2013-05-01

CCAAT/enhancer-binding protein alpha (CEBPA) is a transcription factor involved in adipogenesis and energy homeostasis. Caloric restriction reduces CEBPA protein expression in patients with metabolic syndrome (MetS). A previous report linked rs12691 SNP in CEBPA to altered concentration of fasting triglycerides. Our objective was to assess the effects of rs12691 in glucose metabolism in Metabolic Syndrome (MetS) patients. Glucose metabolism was assessed by static (glucose, insulin, adiponectin, leptin and resistin plasma concentrations) and dynamic (disposition index, insulin sensitivity index, HOMA-IR and acute insulin response to glucose) indices, performed at baseline and after 12 weeks of 4 dietary interventions (high saturated fatty acid (SFA), high monounsaturated fatty acid (MUFA), low-fat and low-fat-high-n3 polyunsaturated fatty acid (PUFA)) in 486 subjects with MetS. Carriers of the minor A allele of rs12691 had altered disposition index (p = 0.0003), lower acute insulin response (p = 0.005) and a lower insulin sensitivity index (p = 0.025) indicating a lower insulin sensitivity and a lower insulin secretion, at baseline and at the end of the diets. Furthermore, A allele carriers displayed lower HDL concentration. The presence of the A allele of rs12691 influences glucose metabolism of MetS patients. Copyright © 2011 Elsevier B.V. All rights reserved.

Impact of Short Term Consumption of Diets High in Either Non-Starch Polysaccharides or Resistant Starch in Comparison with Moderate Weight Loss on Indices of Insulin Sensitivity in Subjects with Metabolic Syndrome

PubMed Central

Lobley, Gerald E.; Holtrop, Grietje; Bremner, David M.; Calder, A. Graham; Milne, Eric; Johnstone, Alexandra M.

2013-01-01

This study investigated if additional non-starch polysaccharide (NSP) or resistant starch (RS), above that currently recommended, leads to better improvement in insulin sensitivity (IS) than observed with modest weight loss (WL). Obese male volunteers (n = 14) were given an energy-maintenance (M) diet containing 27 g NSP and 5 g RS daily for one week. They then received, in a cross-over design, energy-maintenance intakes of either an NSP-enriched diet (42 g NSP, 2.5 g RS) or an RS-enriched diet (16 g NSP, 25 g RS), each for three weeks. Finally, a high protein (30% calories) WL diet was provided at 8 MJ/day for three weeks. During each dietary intervention, endogenous glucose production (EGP) and IS were assessed. Fasting glycaemia was unaltered by diet, but plasma insulin and C-peptide both decreased with the WL diet (p < 0.001), as did EGP (−11%, p = 0.006). Homeostatis model assessment of insulin resistance improved following both WL (p < 0.001) and RS (p < 0.05) diets. Peripheral tissue IS improved only with WL (57%–83%, p < 0.005). Inclusion of additional RS or NSP above amounts currently recommended resulted in little or no improvement in glycaemic control, whereas moderate WL (approximately 3 kg fat) improved IS. PMID:23752495

Transoesophageal detection of heart graft rejection by electrical impedance: Using finite element method simulations

NASA Astrophysics Data System (ADS)

Giovinazzo, G.; Ribas, N.; Cinca, J.; Rosell-Ferrer, J.

2010-04-01

Previous studies have shown that it is possible to evaluate heart graft rejection level using a bioimpedance technique by means of an intracavitary catheter. However, this technique does not present relevant advantages compared to the gold standard for the detection of a heart rejection, which is the biopsy of the endomyocardial tissue. We propose to use a less invasive technique that consists in the use of a transoesophageal catheter and two standard ECG electrodes on the thorax. The aim of this work is to evaluate different parameters affecting the impedance measurement, including: sensitivity to electrical conductivity and permittivity of different organs in the thorax, lung edema and pleural water. From these results, we deduce the best estimator for cardiac rejection detection, and we obtain the tools to identify possible cases of false positive of heart rejection due to other factors. To achieve these objectives we have created a thoracic model and we have simulated, with a FEM program, different situations at the frequencies of 13, 30, 100, 300 and 1000 kHz. Our simulation demonstrates that the phase, at 100 and 300 kHz, has the higher sensitivity to changes in the electrical parameters of the heart muscle.

Multivariate prediction of upper limb prosthesis acceptance or rejection.

PubMed

Biddiss, Elaine A; Chau, Tom T

2008-07-01

To develop a model for prediction of upper limb prosthesis use or rejection. A questionnaire exploring factors in prosthesis acceptance was distributed internationally to individuals with upper limb absence through community-based support groups and rehabilitation hospitals. A total of 191 participants (59 prosthesis rejecters and 132 prosthesis wearers) were included in this study. A logistic regression model, a C5.0 decision tree, and a radial basis function neural network were developed and compared in terms of sensitivity (prediction of prosthesis rejecters), specificity (prediction of prosthesis wearers), and overall cross-validation accuracy. The logistic regression and neural network provided comparable overall accuracies of approximately 84 +/- 3%, specificity of 93%, and sensitivity of 61%. Fitting time-frame emerged as the predominant predictor. Individuals fitted within two years of birth (congenital) or six months of amputation (acquired) were 16 times more likely to continue prosthesis use. To increase rates of prosthesis acceptance, clinical directives should focus on timely, client-centred fitting strategies and the development of improved prostheses and healthcare for individuals with high-level or bilateral limb absence. Multivariate analyses are useful in determining the relative importance of the many factors involved in prosthesis acceptance and rejection.

Genetic Modification of the Relationship between Parental Rejection and Adolescent Alcohol Use.

PubMed

Stogner, John M; Gibson, Chris L

2016-07-01

Parenting practices are associated with adolescents' alcohol consumption, however not all youth respond similarly to challenging family situations and harsh environments. This study examines the relationship between perceived parental rejection and adolescent alcohol use, and specifically evaluates whether youth who possess greater genetic sensitivity to their environment are more susceptible to negative parental relationships. Analyzing data from the National Longitudinal Study of Adolescent Health, we estimated a series of regression models predicting alcohol use during adolescence. A multiplicative interaction term between parental rejection and a genetic index was constructed to evaluate this potential gene-environment interaction. Results from logistic regression analyses show a statistically significant gene-environment interaction predicting alcohol use. The relationship between parental rejection and alcohol use was moderated by the genetic index, indicating that adolescents possessing more 'risk alleles' for five candidate genes were affected more by stressful parental relationships. Feelings of parental rejection appear to influence the alcohol use decisions of youth, but they do not do so equally for all. Higher scores on the constructed genetic sensitivity measure are related to increased susceptibility to negative parental relationships. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Light-controlled resistors provide quadrature signal rejection for high-gain servo systems

NASA Technical Reports Server (NTRS)

Mc Cauley, D. D.

1967-01-01

Servo amplifier feedback system, in which the phase sensitive detection, low pass filtering, and multiplication functions required for quadrature rejection, are preformed by light-controlled photoresistors, eliminates complex circuitry. System increases gain, improves signal-to-noise ratio, and eliminates the necessity for compensation.

Decadal Variability of Surface Incident Solar Radiation over China

NASA Astrophysics Data System (ADS)

Wang, Kaicun

2015-04-01

Observations have reported a widespread dimming of surface incident solar radiation (Rs) from the 1950s to the 1980s and a brightening afterwards. However, none of the state-of-the-art earth system models, including those from the Coupled Model Intercomparison Project phase 5 (CMIP5), could successfully reproduce the dimming/brightening rates over China. This study provides metadata and reference data to investigate the observed variability of Rs in China. From 1958 to 1990, diffuse solar radiation (Rsdif) and direct solar radiation (Rsdir) was measured separately in China, from which Rs was calculated a sum. However, pyranometers used to measure Rsdif had a strong sensitivity drift problem, which introduced a spurious decreasing trend to Rsdif and Rs measurements. The observed Rsdir did not suffer from such sensitivity drift problem. From 1990 to 1993, the old instruments were replaced and measuring stations were relocated in China, which introduced an abrupt increase in the observed Rs. After 1993, Rs was measured by solid black thermopile pyranometers. Comprehensive comparisons between observation-based and model-based Rs performed in this research have shown that sunshine duration (SunDu)-derived Rs is of high quality and provide accurate estimate of decadal variability of Rs over China. SunDu-derived Rs averaged over 105 stations in China decreased at -2.9 W m-2 per decade from 1961 to 1990 and remained stable afterward. This decadal variability has been confirmed by the observed Rsdir, independent studies on aerosols and diurnal temperature range, and can be reproduced by certain high-quality earth system models. However, neither satellite retrievals (the Global Energy and Water Exchanges Project Surface Radiation Budget (GEWEX SRB)) nor reanalyses (ERA-Interim and Modern-Era Retrospective analysis for Research and Applications (MERRA)) can accurately reproduce such decadal variability of Rs over China for their exclusion of annual variability of tropospheric aerosols.

Impulsivity, Rejection Sensitivity, and Reactions to Stressors in Borderline Personality Disorder

PubMed Central

Berenson, Kathy R.; Gregory, Wesley Ellen; Glaser, Erin; Romirowsky, Aliza; Rafaeli, Eshkol; Yang, Xiao; Downey, Geraldine

2016-01-01

This research investigated baseline impulsivity, rejection sensitivity, and reactions to stressors in individuals with borderline personality disorder compared to healthy individuals and those with avoidant personality disorder. The borderline group showed greater impulsivity than the avoidant and healthy groups both in a delay-discounting task with real monetary rewards and in self-reported reactions to stressors; moreover, these findings could not be explained by co-occurring substance use disorders. Distress reactions to stressors were equally elevated in both personality disorder groups (relative to the healthy group). The borderline and avoidant groups also reported more maladaptive reactions to a stressor of an interpersonal vs. non-interpersonal nature, whereas the healthy group did not. Finally, self-reported impulsive reactions to stressors were associated with baseline impulsivity in the delay-discounting task, and greater self-reported reactivity to interpersonal than non-interpersonal stressors was associated with rejection sensitivity. This research highlights distinct vulnerabilities contributing to impulsive behavior in borderline personality disorder. PMID:27616800

Late acute humoral rejection in low-risk renal transplant recipients induced with an interleukin-2 receptor antagonist and maintained with standard therapy: preliminary communication.

PubMed

Morales, J; Contreras, L; Zehnder, C; Pinto, V; Elberg, M; Araneda, S; Herzog, C; Calabran, L; Aguiló, J; Ferrario, M; Buckel, E; Fierro, J A

2011-01-01

Low-risk renal transplant recipients treated with standard immunosuppressive therapy including interleukin-2 receptor (IL-2R) antagonist show a low incidence of early rejection episodes but few reports have examined the incidence and severity of late rejection processes. This study evaluated retrospectively cellular and antibody-mediated rejection (AMR) among 42 recipients selected because they showed low panel-reactive-antibodies, short cold ischemia time, no delayed graft function, and therapy including basiliximab (Simulect) induction. The mean observation time was 6.6 years. Sixty-seven percent of donors were deceased. Ten-year patient and death-censored graft survivals were 81% and 78%, respectively. Seven patients lost their kidneys due to nonimmunologic events. The seven recipients who experienced cellular rejection episodes during the first posttransplant year had them reversed with steroids. Five patients displayed late acute AMR causing functional deterioration in four cases including 1 graft loss. De novo sensitization occurred in 48% of recipients including patients without clinical rejection. In conclusion, long-term follow-up of kidney transplant recipients selected by a low immunologic risk showed a persistent risk of de novo sensitization evolving to acute AMR in 11% of cases. Although immunologic events were related to late immunosuppressive reduction, most graft losses were due to nonimmunologic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparative immunohistologic studies in an adoptive transfer model of acute rat cardiac allograft rejection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forbes, R.D.; Lowry, R.P.; Gomersall, M.

1985-07-01

It has been shown that fulminant acute rejection of rat cardiac allografts across a full haplotype disparity may occur as a direct result of adoptive transfer of sensitized W3/25+ MRC OX8- SIg- T helper/DTH syngeneic spleen cells to sublethally irradiated recipients. In order to establish the immunohistologic parameters of this form of rejection, allografts and recipient lymphoid tissue were analyzed using a panel of monoclonal antibodies of known cellular distribution. These data were compared with those obtained following reconstitution of irradiated allograft recipients with unseparated sensitized spleen cells, with unreconstituted irradiated donor recipient pairs, with unmodified first-set rejection, and withmore » induced myocardial infarction of syngeneic heart grafts transplanted to normal and to sublethally irradiated recipients. Rejecting cardiac allografts transplanted to all reconstituted irradiated recipients were characterized by extensive infiltration with MRC OX8+ (T cytotoxic-suppressor, natural killer) cells even when this subset was virtually excluded from the reconstituting inocula. A similar proportional accumulation of MRC OX8+ cells observed at the infarct margins of syngeneic heart grafts transplanted to irradiated unreconstituted recipients greatly exceeded that present in normal nonirradiated controls. These data provide evidence that under conditions of heavy recipient irradiation, MRC OX8+ cells may be sequestered within heart grafts in response to nonspecific injury unrelated to the rejection process.« less

Soil respiration and carbon loss relationship with temperature and land use conversion in freeze-thaw agricultural area.

PubMed

Ouyang, Wei; Lai, Xuehui; Li, Xia; Liu, Heying; Lin, Chunye; Hao, Fanghua

2015-11-15

Soil respiration (Rs) was hypothesized to have a special response pattern to soil temperature and land use conversion in the freeze-thaw area. The Rs differences of eight types of land use conversions during agricultural development were observed and the impacts of Rs on soil organic carbon (SOC) loss were assessed. The land use conversions during last three decades were categorized into eight types, and the 141 SOC sampling sites were grouped by conversion type. The typical soil sampling sites were subsequently selected for monitoring of soil temperature and Rs of each land use conversion types. The Rs correlations with temperature at difference depths and different conversion types were identified with statistical analysis. The empirical mean error model and the biophysical theoretical model with Arrhenius equation about the Rs sensitivity to temperature were both analyzed and shared the similar patterns. The temperature dependence of soil respiration (Q10) analysis further demonstrated that the averaged value of eight types of land use in this freeze-thaw agricultural area ranged from 1.15 to 1.73, which was lower than the other cold areas. The temperature dependence analysis demonstrated that the Rs in the top layer of natural land covers was more sensitive to temperature and experienced a large vertical difference. The natural land covers exhibited smaller Rs and the farmlands had the bigger value due to tillage practices. The positive relationships between SOC loss and Rs were identified, which demonstrated that Rs was the key chain for SOC loss during land use conversion. The spatial-vertical distributions of SOC concentration with the 1.5-km grid sampling showed that the more SOC loss in the farmland, which was coincided with the higher Rs in farmlands. The analysis of Rs dynamics provided an innovative explanation for SOC loss in the freeze-thaw agricultural area. The analysis of Rs dynamics provided an innovative explanation for SOC loss in the freeze-thaw agricultural area. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Sex and Stress on Trigeminal Neuropathic Pain-Like Behavior in Rats.

PubMed

Korczeniewska, Olga Anna; Khan, Junad; Tao, Yuanxiang; Eliav, Eli; Benoliel, Rafael

2017-01-01

To investigate the effects and interactions of sex and stress (provoked by chronic restraint [RS]) on pain-like behavior in a rat model of trigeminal neuropathic pain. The effects of sex and RS (carried out for 14 days as a model for stress) on somatosensory measures (reaction to pinprick, von Frey threshold) in a rat model of trigeminal neuropathic pain were examined. The study design was 2 × 4, with surgery (pain) and sham surgery (no pain) interacting with male restrained (RS) and unrestrained (nRS) rats and female RS and nRS rats. A total of 64 Sprague Dawley rats (32 males and 32 females) were used. Half of the animals in each sex group underwent RS, and the remaining half were left unstressed. Following the RS period, trigeminal neuropathic pain was induced by unilateral infraorbital nerve chronic constriction injury (IOCCI). Half of the animals in the RS group and half in the nRS group (both males and females) were exposed to IOCCI, and the remaining halves to sham surgery. Elevated plus maze (EPM) assessment and plasma interferon gamma (IFN-γ) levels were used to measure the effects of RS. Analysis of variance (ANOVA) was used to assess the effects of stress, sex, and their interactions on plasma IFN-γ levels, changes in body weight, EPM parameters, tactile allodynia, and mechanohyperalgesia. Pairwise comparisons were performed by using Tukey post hoc test corrected for multiple comparisons. Both male and female RS rats showed significantly altered exploratory behavior (as measured by EPM) and had significantly lower plasma IFN-γ levels than nRS rats. Rats exposed to RS gained weight significantly slower than the nRS rats, irrespective of sex. Following RS but before surgery, RS rats showed significant bilateral reductions in von Frey thresholds and significantly increased pinprick response difference scores compared to nRS rats, irrespective of sex. From 17 days postsurgery, RSIOCCI rats showed significantly reduced von Frey thresholds and significantly increased pinprick response difference scores compared to nRS-IOCCI rats, and the von Frey thresholds were significantly lower in females than in males. RS-sham females-but not RS-sham males-developed persistently reduced thresholds and increased pinprick response difference scores. RS produced an increased bilateral sensitivity to stimuli applied to the vibrissal pad following infraorbital nerve injury, irrespective of sex. This observed sensitivity subsequently persisted in RS-sham female rats but not in RS-sham male rats. Stress induced a significant but moderate increase in pain-like behavior in female rats compared to male rats. RS had no significant sex effects on IFN-γ levels, EPM parameters, or body weight gain. This suggests that stress may have a selective effect on pain-like behavior in both sexes, but the possible mechanisms are unclear.

Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A Study in a Chinese Uygur Population.

PubMed

Han, Zhi-Gang; Tao, Jie; Yu, Ting-Ting; Shan, Li

2017-04-26

BACKGROUND Gene polymorphisms are associated with sensitivity to platinum drugs. This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2 rs717620 locus, and the sensitivity of patients with advanced non-small cell lung cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. MATERIAL AND METHODS The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the prognosis of advanced NSCLC Uygur patients and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was analyzed using progression-free survival (PFS) and overall survival (OS) as the major outcome indicators. RESULTS The median PFS of patients with advanced NSCLC was 6.9 months and the OS of Uygur patients with advanced NSCLC was 10.8 months. Kaplan-Meier survival analysis indicated that survival time of patients with GSTP1 AG + GG was significantly longer than in patients with AA gene (P<0.05), and survival time of patients with ABCC2 CT + TT was significantly longer than in patients with the CC gene (P<0.05). CONCLUSIONS Polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 can be used to predict the outcomes of Uygur patients with advanced NSCLC who have received platinum-based chemotherapy. Additionally, this information could be used to guide the individualized treatment of Uygur patients with advanced NSCLC.

KRAS polymorphisms are associated with survival of CRC in Chinese population.

PubMed

Dai, Qiong; Wei, Hui Lian; Huang, Juan; Zhou, Tie Jun; Chai, Li; Yang, Zhi-Hui

2016-04-01

rs12245, rs12587, rs9266, rs1137282, rs61764370, and rs712 of KRAS oncogene are characterized in the 3'UTR. The study highlights the important role of these polymorphisms playing in the susceptibility, oxaliplatin-based chemotherapy sensitivity, progression, and prognosis of CRC. Improved multiplex ligation detection reaction (iMLDR) technique is used for genotyping. An unconditional logistic regression model was used to estimate the association of certain polymorphism and CRC risk. The Kaplan-Meier method, log-rank test, and Cox regression model were used to evaluate the effects of polymorphisms on survival analysis. Results demonstrated that TT genotype and T allele of rs712 were associated with the increased risk of CRC; the patients with GG genotype and G allele of rs61764370 had a shorter survival and a higher risk of relapse or metastasis of CRC. Our studies supported the conclusions that rs61764370 and rs712 polymorphisms of the KRAS are functional and it may play an important role in the development of CRC and oxaliplatin-based chemotherapy efficiency and prognosis of CRC.

An investigation of error correcting techniques for OMV data

NASA Technical Reports Server (NTRS)

Ingels, Frank; Fryer, John

1992-01-01

Papers on the following topics are presented: considerations of testing the Orbital Maneuvering Vehicle (OMV) system with CLASS; OMV CLASS test results (first go around); equivalent system gain available from R-S encoding versus a desire to lower the power amplifier from 25 watts to 20 watts for OMV; command word acceptance/rejection rates for OMV; a memo concerning energy-to-noise ratio for the Viterbi-BSC Channel and the impact of Manchester coding loss; and an investigation of error correcting techniques for OMV and Advanced X-ray Astrophysics Facility (AXAF).

Statistics Programs for the TI-59 Calculator.

DTIC Science & Technology

1980-12-01

1153123448 u = .1152991877 2. In a survey of dieting effects , ten women were selected, weighed and placed on a diet for two weeks. At the end of that...using El store ( = .2 in R07 (3) Press I is displayed (reject H.), Xt sl = .0253472347 , 2. A new fad diet was tried out on 15 subjects and the weight...after one week on the diet is at least two pounds. Do the data support the claim?(C(= .05) SOLUTION: Ho /12 Hyg 2 (1) Press J , 2, R7 , .05, R/S , 1

Tip-enhanced near-field Raman spectroscopy with a scanning tunneling microscope and side-illumination optics.

PubMed

Yi, K J; He, X N; Zhou, Y S; Xiong, W; Lu, Y F

2008-07-01

Conventional Raman spectroscopy (RS) suffers from low spatial resolution and low detection sensitivity due to the optical diffraction limit and small interaction cross sections. It has been reported that a highly localized and significantly enhanced electromagnetic field could be generated in the proximity of a metallic tip illuminated by a laser beam. In this study, a tip-enhanced RS system was developed to both improve the resolution and enhance the detection sensitivity using the tip-enhanced near-field effects. This instrument, by combining RS with a scanning tunneling microscope and side-illumination optics, demonstrated significant enhancement on both optical sensitivity and spatial resolution using either silver (Ag)-coated tungsten (W) tips or gold (Au) tips. The sensitivity improvement was verified by observing the enhancement effects on silicon (Si) substrates. Lateral resolution was verified to be below 100 nm by mapping Ag nanostructures. By deploying the depolarization technique, an apparent enhancement of 175% on Si substrates was achieved. Furthermore, the developed instrument features fast and reliable optical alignment, versatile sample adaptability, and effective suppression of far-field signals.

Peer acceptance and rejection through the eyes of youth: pupillary, eyetracking and ecological data from the Chatroom Interact task

PubMed Central

Stroud, Laura R.; Siegle, Greg J.; Dahl, Ronald E.; Lee, Kyung Hwa; Nelson, Eric E.

2012-01-01

We developed an ecologically valid virtual peer interaction paradigm—the Chatroom Interact Task in which 60 pre-adolescents and adolescents (ages 9–17 years) were led to believe that they were interacting with other youth in a simulated internet chatroom. Youth received rejection and acceptance feedback from virtual peers. Findings revealed increased pupil dilation, an index of increased activity in cognitive and affective processing regions of the brain, to rejection compared to acceptance trials, which was greater for older youth. Data from a cell-phone Ecological Momentary Assessment (EMA) protocol completed following the task indicated that increased pupillary reactivity to rejection trials was associated with lower feelings of social connectedness with peers in daily life. Eyetracking analyses revealed attentional biases toward acceptance feedback and away from rejection feedback. Biases toward acceptance feedback were stronger for older youth. Avoidance of rejection feedback was strongest among youth with increased pupillary reactivity to rejection, even in the seconds leading up to and following rejection feedback. These findings suggest that adolescents are sensitive to rejection feedback and seek to anticipate and avoid attending to rejection stimuli. Furthermore, the salience of social rejection and acceptance feedback appears to increase during adolescence. PMID:21775386

[Husband to wife kidney transplantation in five multiparous women: sensitization or tolerance after pregnancy?].

PubMed

Ortiz-Arroyo, Víctor M; Granados, Julio; Uribe-Uribe, Norma; de Leo, Claudia; Castelán, Natalia; González, Norma; López, Mayra; Alberú, Josefina

2004-01-01

Pregnancy is a known cause of immunological sensitization and it has been reported graft survival to be lower in husband to wife kidney transplantation if the wife had been pregnant (mutual children) as compare to those cases without pregnancies. Previous exposure to husband HLA antigens during pregnancies may lead to specific sensitization to subsequent allografts. To communicate the fate of kidney allograft in husband to wife transplantation when the recipient had been pregnant. From 682 renal transplants performed at INCMNSZ 5 corresponded to husband to wife transplants. All the recipients were multiparous and had received multiple blood transfusions. Pretransplantation lymphocytotoxic cross-match testing were performed by complement dependent citotoxicity with antihuman globulin added (AHG-CDC), being negative in all cases for T and B cells. All the patients received triple-drug immunosuppressive therapy, additionally, anti-IL2R monoclonal antibodies were used in two cases. Two patients developed: accelerated acute rejection (case 1), and acute humoral rejection (case 5), respectively. Graft in these patients were loss to rejection and transplant nephrectomy accomplished. The remaining three patients (cases 2, 3, and 4) has not had any rejection episode, and have had excellent graft outcome at 34, 30, and 21 months posttransplant, respectively. Why under similar conditions some husband to wife kidney transplant recipients developed an adverse humoral immunological events while others maintain excellent long-term graft outcome? Is it possible to speculate that for some women pregnancy is in fact a sensitizing event, while in others it promotes "immunological acceptance"? At present there is no a test that characterized one and other group. Even though pretransplantation cross-match testing by flow cytometry is more sensitive than AHG-CDC, its negative result is by no means an absolute guarantee that an adverse anamnestic immunological event will not occur.

Sensitivity of neuronal nicotinic acetylcholine receptors to the opiate antagonists naltrexone and naloxone: receptor blockade and up-regulation.

PubMed

Almeida, Luis E F; Pereira, Edna F R; Camara, Adriana L; Maelicke, Alfred; Albuquerque, Edson X

2004-04-19

In HEK293 cells stably expressing alpha4beta2 nAChRs, naltrexone, but not naloxone, blocked alpha4beta2 nAChRs via an open-channel blocking mechanism. In primary hippocampal cultures, naltrexone inhibited alpha7 nAChRs up-regulated by nicotine, and in organotypic hippocampal cultures naltrexone caused a time-dependent up-regulation of functional alpha7 nAChRs that was detected after removal of the drug. These results indicate that naltrexone could be used as a smoking cessation aid.

Therapeutic potential of microRNAs in heart failure.

PubMed

Dorn, Gerald W

2010-05-01

There is an ongoing explosion of information about microRNAs (miRs) in cardiac disease. These small noncoding RNAs regulate protein expression by destabilization and translational inhibition of target mRNAs. Similar to mRNAs, miRs are regulated in cardiac hypertrophy and heart failure, but miR expression profiles appear to be more sensitive than mRNA signatures to changes in clinical status, suggesting that miR levels in myocardium or plasma could enhance clinical diagnostics. Single miRs can target dozens or hundreds of different mRNAs, complicating attempts to determine their individual physiologic effects. However, manipulating individual miRs by overexpression or gene ablation in experimental models has begun to unravel this conundrum: Single miRs tend to regulate numerous effectors within the same functional pathway, producing a coherent physiologic response via multiple parallel perturbations. miRs are attractive nodal therapeutic targets, and stable miR mimetics (agomiRs) and antagonists (antagomiRs) are being evaluated to prevent or reverse heart failure.

Expression of Functional Human α6β2β3* Acetylcholine Receptors in Xenopus laevis Oocytes Achieved through Subunit Chimeras and Concatamers

PubMed Central

Kuryatov, Alexandre

2011-01-01

α6β2β3* acetylcholine receptors (AChRs) on dopaminergic neurons are important targets for drugs to treat nicotine addiction and Parkinson's disease. However, it has not been possible to efficiently express functional α6β2β3* AChRs in oocytes or transfected cells. α6/α3 subunit chimeras permit expression of functional AChRs and reveal that parts of the α6 M1 transmembrane domain and large cytoplasmic domain impair assembly. Concatameric subunits permit assembly of functional α6β2β3* AChRs with defined subunit compositions and subunit orders. Assembly of accessory subunits is limiting in formation of mature AChRs. A single linker between the β3 accessory subunit and an α4 or α6 subunit is sufficient to permit assembly of complex β3-(α4β2)(α6β2) or β3-(α6β2)(α4β2) AChRs. Concatameric pentamers such as β3-α6-β2-α4-β2 have been functionally characterized. α6β2β3* AChRs are sensitive to activation by drugs used for smoking cessation therapy (nicotine, varenicline, and cytisine) and by sazetidine. All these are partial agonists. (α6β2)(α4β2)β3 AChRs are most sensitive to agonists. (α6β2)2β3 AChRs have the greatest Ca2+ permeability. (α4β2)(α6β2)β3 AChRs are most efficiently transported to the cell surface, whereas (α6β2)2β3 AChRs are the least efficiently transported. Dopaminergic neurons may have special chaperones for assembling accessory subunits with α6 subunits and for transporting (α6β2)2β3 AChRs to the cell surface. Concatameric pentamers and pentamers formed from combinations of trimers, dimers, and monomers exhibit similar properties, indicating that the linkers between subunits do not alter their functional properties. For the first time, these concatamers allow analysis of functional properties of α6β2β3* AChRs. These concatamers should enable selection of drugs specific for α6β2β3* AChRs. PMID:20923852

Genetic Determinants of Enterovirus Infections: Polymorphisms in Type 1 Diabetes and Innate Immune Genes in the MIDIA Study.

PubMed

Witsø, Elisabet; Cinek, Ondrej; Tapia, German; Brorsson, Caroline A; Stene, Lars C; Gjessing, Håkon K; Rasmussen, Trond; Bergholdt, Regine; Pociot, Flemming M; Rønningen, Kjersti S

2015-12-01

Enteroviruses have been suggested as triggers of type 1 diabetes (T1D). We aimed to assess whether established T1D susceptibility single nucleotide polymorphisms (SNPs) and candidate SNPs in innate immune genes were associated with the frequency of enterovirus infection in otherwise healthy children. Fifty-six established T1D SNPs and 97 other candidate immunity SNPs were typed in 419 children carrying the T1D high-risk genotype, HLA-DR4-DQ8/DR3-DQ2 genotype, and 373 children without this genotype. Enteroviral RNA was detected using real-time polymerase chain reaction, with primers detecting essentially all enterovirus serotypes, in 7,393 longitudinal stool samples collected monthly (age range 3-36 months). The most significant association was with two T1D SNPs, rs12150079 (ZPBP2/ORMDL3/GSDMB region) (enterovirus frequency: AA 7.3%, AG 8.7%, GG 9.7%, RR = 0.86, overall p = 1.87E-02) and rs229541 (C1QTNF6/SSTR3/RAC2) (enterovirus frequency: CC 7.8%, CT 9.7%, TT 9.4%, RR = 1.13, overall p = 3.6E-02), followed by TLR8 (rs2407992) (p = 3.8E-02), TLR3 (1914926) (p = 4.9E-02), and two other T1D SNPs (IFIH1 rs3747517, p = 4.9E-02 and PTPN22, rs2476601, p = 5.3E-02). However, the quantile-quantile plot of p-values with confidence intervals for all 153 SNPs did not reveal clear evidence for rejection of the complete null hypothesis. Among a number of SNPs in candidate genes, we found no evidence for strong associations with enterovirus presence in stool samples from Norwegian children.

Investigating hypervigilance for social threat of lonely children.

PubMed

Qualter, Pamela; Rotenberg, Ken; Barrett, Louise; Henzi, Peter; Barlow, Alexandra; Stylianou, Maria; Harris, Rebecca A

2013-02-01

The hypothesis that lonely children show hypervigilance for social threat was examined in a series of three studies that employed different methods including advanced eye-tracking technology. Hypervigilance for social threat was operationalized as hostility to ambiguously motivated social exclusion in a variation of the hostile attribution paradigm (Study 1), scores on the Children's Rejection-Sensitivity Questionnaire (Study 2), and visual attention to socially rejecting stimuli (Study 3). The participants were 185 children (11 years-7 months to 12 years-6 months), 248 children (9 years-4 months to 11 years-8 months) and 140 children (8 years-10 months to 12 years-10 months) in the three studies, respectively. Regression analyses showed that, with depressive symptoms covaried, there were quadratic relations between loneliness and these different measures of hypervigilance to social threat. As hypothesized, only children in the upper range of loneliness demonstrated elevated hostility to ambiguously motivated social exclusion, higher scores on the rejection sensitivity questionnaire, and disengagement difficulties when viewing socially rejecting stimuli. We found that very lonely children are hypersensitive to social threat.

LVAD Implant as a Bridge to Heart Transplantation is Associated with Allosensitization as Measured by Single Antigen Bead Assay

PubMed Central

Shankar, Nisha; Daly, Richard; Geske, Jennifer; Kushwaha, Sudhir K; Timmons, Michael; Joyce, Lyle; Stulak, John; Gandhi, Manish; Kremers, Walter; Park, Soon; Pereira, Naveen L

2013-01-01

Background Left ventricular assist devices (LVAD) as a bridge (BTT) to heart transplantation (HTX) may be limited by the formation of anti-HLA antibodies. Whether sensitization occurs with continuous axial flow LVAD implant as assessed by Single Antigen Bead (SAB) assay is unknown. Methods Cytotoxic panel reactive antibody (PRA) and SAB assays were analyzed in HTX recipients undergoing LVAD implant as a BTT. Sensitization was defined as peak anti-HLA antibody values of >2000 mean fluorescent intensity as these values have been found to correlate with flow cytometric crossmatch results. Results LVADs were implanted as BTT in 30 patients. There were 7% (2/30) of patients prior to and no patients after LVAD implant with PRA >10%. However, 20% (6/30) of patients prior to and 53% (16/30) after LVAD were sensitized as measured by SAB (p=0.024). At HTX, 47% (14/30) of patients remained sensitized. A positive virtual crossmatch was observed in 28% (4/14) of the sensitized patients at HTX. There was no difference between the sensitized and non-sensitized groups (p>0.4 for all) in usage of blood products (64 11 vs. 63 39 units), time to HTX (286 63 vs. 257 48 days) and 1 year after HTX, there were no differences in rejection (total rejection score 0.30 vs. 0.37) and survival (93% vs. 88%). Conclusion Allosensitization after LVAD is common despite cytotoxic PRA being negative. One year after HTX, this sensitization does not translate into increased acute cellular or antibody mediated rejection or reduced survival. PMID:23743727

Soluble CD30 correlates with clinical but not subclinical renal allograft rejection.

PubMed

Hirt-Minkowski, Patricia; Roth, Michèle; Hönger, Gideon; Amico, Patrizia; Hopfer, Helmut; Schaub, Stefan

2013-01-01

Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for clinical renal allograft rejection, but its diagnostic characteristics regarding detection of subclinical rejection have not been assessed. We investigated sCD30 in 146 consecutive kidney allograft recipients under tacrolimus-mycophenolate-based immunosuppression having 250 surveillance biopsies at 3 and 6 months as well as 52 indication biopsies within the first year post-transplant. Allograft histology results were classified as (i) acute Banff score zero or interstitial infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2-3 and (iv) isolated vascular compartment inflammation. sCD30 correlated well with the extent of clinical (P < 0.0001), but not subclinical tubulointerstitial rejection (P = 0.06). To determine diagnostic characteristics of sCD30, histological groups were assigned to two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (tubulitis t1-3 and isolated vascular compartment inflammation). For clinical allograft inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006); however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%, specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but not subclinical renal allograft rejection limiting its clinical utility as a noninvasive rejection screening biomarker in patients with stable allograft function receiving tacrolimus-mycophenolate-based immunosuppression. © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.

Polymorphisms in Fatty Acid Desaturase (FADS) Gene Cluster: Effects on Glycemic Controls Following an Omega-3 Polyunsaturated Fatty Acids (PUFA) Supplementation.

PubMed

Cormier, Hubert; Rudkowska, Iwona; Thifault, Elisabeth; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-09-10

Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g-2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). RESULTS suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation.

Polymorphisms in Fatty Acid Desaturase (FADS) Gene Cluster: Effects on Glycemic Controls Following an Omega-3 Polyunsaturated Fatty Acids (PUFA) Supplementation

PubMed Central

Cormier, Hubert; Rudkowska, Iwona; Thifault, Elisabeth; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-01-01

Changes in desaturase activity are associated with insulin sensitivity and may be associated with type 2 diabetes mellitus (T2DM). Polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster have been associated with the homeostasis model assessment of insulin sensitivity (HOMA-IS) and serum fatty acid composition. Objective: To investigate whether common genetic variations in the FADS gene cluster influence fasting glucose (FG) and fasting insulin (FI) responses following a 6-week n-3 polyunsaturated fatty acids (PUFA) supplementation. Methods: 210 subjects completed a 2-week run-in period followed by a 6-week supplementation with 5 g/d of fish oil (providing 1.9 g–2.2 g of EPA + 1.1 g of DHA). Genotyping of 18 SNPs of the FADS gene cluster covering 90% of all common genetic variations (minor allele frequency ≥ 0.03) was performed. Results: Carriers of the minor allele for rs482548 (FADS2) had increased plasma FG levels after the n-3 PUFA supplementation in a model adjusted for FG levels at baseline, age, sex, and BMI. A significant genotype*supplementation interaction effect on FG levels was observed for rs482548 (p = 0.008). For FI levels, a genotype effect was observed with one SNP (rs174456). For HOMA-IS, several genotype*supplementation interaction effects were observed for rs7394871, rs174602, rs174570, rs7482316 and rs482548 (p = 0.03, p = 0.01, p = 0.03, p = 0.05 and p = 0.07; respectively). Conclusion: Results suggest that SNPs in the FADS gene cluster may modulate plasma FG, FI and HOMA-IS levels in response to n-3 PUFA supplementation. PMID:24705214

Examining the Causal Role of Leptin in Alzheimer Disease: A Mendelian Randomization Study.

PubMed

Romo, Matthew L; Schooling, C Mary

2017-01-01

Observational evidence regarding the role of leptin in Alzheimer disease (AD) is conflicting. We sought to determine the causal role of circulating leptin and soluble plasma leptin receptor (sOB-R) levels in AD using a separate-sample Mendelian randomization study. Single nucleotide polymorphisms (SNPs) independently and solely predictive of log-transformed leptin (rs10487505 [LEP], rs780093 [GCKR], rs900400 [CCNL1], rs6071166 [SLC32A1], and rs6738627 [COBLL1]) and of sOB-R (rs1137101 [LEPR], rs2767485 [LEPR], and rs1751492 [LEPR]) levels (ng/mL) were obtained from 2 previously reported genome-wide association studies. We obtained associations of leptin and sOB-R levels with AD using inverse variance weighting with fixed effects by combining Wald estimates for each SNP. Sensitivity analyses included using weighted median and MR-Egger methods and repeating the analyses using only SNPs of genome-wide significance. Using inverse variance weighting, genetically predicted circulating leptin levels were not associated with AD, albeit with wide confidence intervals (CIs): odds ratio (OR) 0.99 per log-transformed ng/mL; 95% CI 0.55-1.78. Similarly, the association of sOB-R with AD was null using inverse variance weighting (OR 1.08 per log-transformed ng/mL; 95% CI 0.83-1.41). Results from our sensitivity analyses confirmed our findings. In this first Mendelian randomization study estimating the causal effect of leptin on AD, we did not find an effect of genetically predicted circulating leptin and sOB-R levels on AD. As such, this study suggests that leptin is unlikely to be a major contributor to AD, although the wide CIs preclude a definitive assessment. © 2017 S. Karger AG, Basel.

Use of a SQUID array to detect T-cells with magnetic nanoparticles in determining transplant rejection

NASA Astrophysics Data System (ADS)

Flynn, Edward R.; Bryant, H. C.; Bergemann, Christian; Larson, Richard S.; Lovato, Debbie; Sergatskov, Dmitri A.

2007-04-01

Acute rejection in organ transplant is signaled by the proliferation of T-cells that target and kill the donor cells requiring painful biopsies to detect rejection onset. An alternative non-invasive technique is proposed using a multi-channel superconducting quantum interference device (SQUID) magnetometer to detect T-cell lymphocytes in the transplanted organ labeled with magnetic nanoparticles conjugated to antibodies specifically attached to lymphocytic ligand receptors. After a magnetic field pulse, the T-cells produce a decaying magnetic signal with a characteristic time of the order of a second. The extreme sensitivity of this technique, 10 5 cells, can provide early warning of impending transplant rejection and monitor immune-suppressive chemotherapy.

Prescribed burning and mechanical thinning effects on belowground conditions and soil respiration in a mixed-conifer forest, California

Treesearch

Soung-Ryoul Ryu; Amy Concilio; Jiquan Chen; Malcolm North; Siyan Ma

2009-01-01

Soil respiration (RS) is a major carbon pathway from terrestrial ecosystems to the atmosphere and is sensitive to environmental changes. Although commonly used mechanical thinning and prescribed burning can significantly alter the soil environment, the effect of these practices on RS...

Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation

PubMed Central

Ruiz, Jesus; Herrero, María José; Bosó, Virginia; Megías, Juan Eduardo; Hervás, David; Poveda, Jose Luis; Escrivá, Juan; Pastor, Amparo; Solé, Amparo; Aliño, Salvador Francisco

2015-01-01

Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C0/Dc). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation. PMID:26307985

Peer Rejection Cues Induce Cardiac Slowing after Transition into Adolescence

ERIC Educational Resources Information Center

Gunther Moor, Bregtje; Bos, Marieke G. N.; Crone, Eveline A.; van der Molen, Maurits W.

2014-01-01

The present study examined developmental and gender differences in sensitivity to peer rejection across the transition into adolescence by examining beat-by-beat heart rate responses. Children between the ages of 8 and 14 years were presented with unfamiliar faces of age-matched peers and were asked to predict whether they would be liked by the…

Multimodal physiological sensor for motion artefact rejection.

PubMed

Goverdovsky, Valentin; Looney, David; Kidmose, Preben; Mandic, Danilo P

2014-01-01

This work introduces a novel physiological sensor, which combines electrical and mechanical modalities in a co-located arrangement, to reject motion-induced artefacts. The mechanically sensitive element consists of an electret condenser microphone containing a light diaphragm, allowing it to detect local mechanical displacements and disregard large-scale whole body movements. The electrically sensitive element comprises a highly flexible membrane, conductive on one side and insulating on the other. It covers the sound hole of the microphone, thereby forming an isolated pocket of air between the membrane and the diaphragm. The co-located arrangement of the modalities allows the microphone to sense mechanical disturbances directly through the electrode, thus providing an accurate proxy to artefacts caused by relative motion between the skin and the electrode. This proxy is used to reject such artefacts in the electrical physiological signals, enabling enhanced recording quality in wearable health applications.

Rejection of Alpha Surface Background in Non-scintillating Bolometric Detectors: The ABSuRD Project

DOE PAGES

Biassoni, M.; Brofferio, C.; Bucci, C.; ...

2016-01-14

Due to their excellent energy resolution values and the vast choice of possible materials, bolometric detectors are currently widely used in the physics of rare events. A limiting aspect for bolometers rises from their inability to discriminate among radiation types or surface from bulk events. It has been demonstrated that the main limitation to sensitivity for purely bolometric detectors is represented by surface alpha contaminations, causing a continuous background that cannot be discriminated. A new scintillation based technique for the rejection of surface alpha background in non- scintillating bolometric experiments is proposed in this work. The idea is to combinemore » a scintillating and a high sensitivity photon detector with a non- scintillating absorber. Finally, we present results showing the possibility to reject events due to alpha decay at or nearby the surface of the crystal.« less

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

PubMed

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Genetic variation in CYP4A11 and blood pressure response to mineralocorticoid receptor antagonism or ENaC inhibition: an exploratory pilot study in African Americans.

PubMed

Laffer, Cheryl L; Elijovich, Fernando; Eckert, George J; Tu, Wanzhu; Pratt, J Howard; Brown, Nancy J

2014-07-01

An rs3890011 variant of CYP4A11, which is in linkage disequilibrium with the loss-of-function variant rs1126742, is associated with hypertension in humans. In mice, Cyp4a deficiency results in salt-sensitive hypertension through activation of ENaC. We tested the hypothesis that the rs3890011 variant is associated with blood pressure response to drugs acting via the ENaC pathway. African Americans with volume-dependent, resistant hypertension were randomized to treatment with placebo, spironolactone, amiloride, or combination. Blood pressure responses were analyzed by CYP4A11 genotypes. Rs3890011 (GG:GC:CC = 20:35:28) and rs1126742 (TT:TC:CC = 45:31:7) were in linkage disequilibrium (D' = 1, r = 0.561). Expected small number of rs1126742 CC homozygotes precluded analysis of the effect of this genotype on treatment responses. Spironolactone reduced blood pressure in rs3890011 GG and GC individuals, but not in CC homozygotes (P = .002), whereas amiloride reduced blood pressure similarly in all rs3890011 genotypes. The antihypertensive effects of spironolactone and amiloride were comparable in GG and GC participants, but only amiloride reduced pressure in CC homozygotes (-6.3 ± 7.3/-3.2 ± 4.0 vs. +6.8 ± 7.9/+4.8 ± 8.6 mm Hg, P < .01/<.05). The aldosterone response to spironolactone was also blunted in the CC genotype. In individuals homozygous for the CYP4A11 rs3890011 C allele, blood pressure is resistant to mineralocorticoid receptor antagonism, but sensitive to ENaC inhibition, consistent with ENaC activation. Studies in a larger population are needed to replicate these findings. Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Preparation and Characterization of Cyclotrimethylenetrinitramine (RDX) with Reduced Sensitivity

PubMed Central

Wang, Yuqiao; Li, Xin; Chen, Shusen; Ma, Xiao; Yu, Ziyang; Jin, Shaohua; Li, Lijie; Chen, Yu

2017-01-01

The internal defects and shape of cyclotrimethylenetrinitramine (RDX) crystal are critical parameters for the preparation of reduced sensitivity RDX (RS-RDX). In the current study, RDX was re-crystallized and spheroidized to form the high-quality RDX that was further characterized by purity, apparent density, size distribution, specific surface area, impact sensitivity, and shock sensitivity. The effects of re-crystallization solvent on the growth morphology of RDX crystal were investigated by both theoretical simulation and experiment test, and consistent results were obtained. The high-quality RDX exhibited a high purity (≥99.90%), high apparent density (≥1.811 g/cm3), spherical shape, and relatively low impact sensitivity (6%). Its specific surface area was reduced more than 30%. Compared with conventional RDXs, the high-quality RDX reduced the shock sensitivities of PBXN-109 and PBXW-115 by more than 30%, indicating that it was a RS-RDX. The reduced sensitivity and good processability of the high-quality RDX would be significant in improving the performances of RDX-based PBXs. PMID:28825661

Some comments on Hurst exponent and the long memory processes on capital markets

NASA Astrophysics Data System (ADS)

Sánchez Granero, M. A.; Trinidad Segovia, J. E.; García Pérez, J.

2008-09-01

The analysis of long memory processes in capital markets has been one of the topics in finance, since the existence of the market memory could implicate the rejection of an efficient market hypothesis. The study of these processes in finance is realized through Hurst exponent and the most classical method applied is R/S analysis. In this paper we will discuss the efficiency of this methodology as well as some of its more important modifications to detect the long memory. We also propose the application of a classical geometrical method with short modifications and we compare both approaches.

Neural responses to witnessing peer rejection after being socially excluded: fMRI as a window into adolescents’ emotional processing

PubMed Central

Masten, Carrie L.; Eisenberger, Naomi I.; Pfeifer, Jennifer H.; Dapretto, Mirella

2013-01-01

During adolescence, concerns about peer rejection and acceptance become increasingly common. Adolescents regularly experience peer rejection firsthand and witness these behaviors among their peers. In the current study, neuroimaging techniques were employed to conduct a preliminary investigation of the affective and cognitive processes involved in witnessing peer acceptance and rejection—specifically when these witnessed events occur in the immediate aftermath of a firsthand experience with rejection. During an fMRI scan, twenty-three adolescents underwent a simulated experience of firsthand peer rejection. Then, immediately following this experience they watched as another adolescent was ostensibly first accepted and then rejected. Findings indicated that in the immediate aftermath of being rejected by peers, adolescents displayed neural activity consistent with distress when they saw another peer being accepted, and neural activity consistent with emotion regulation and mentalizing (e.g., perspective-taking) processes when they saw another peer being rejected. Furthermore, individuals displaying a heightened sensitivity to firsthand rejection were more likely to show neural activity consistent with distress when observing a peer being accepted. Findings are discussed in terms of how witnessing others being accepted or rejected relates to adolescents’ interpretations of both firsthand and observed experiences with peers. Additionally, the potential impact that witnessed events might have on the broader perpetuation of bullying at this age is also considered. PMID:24033579

[Detection of nitrite and nitrosocompounds in chemical systems and biological liquids by the calorimetric method].

PubMed

Titov, V Iu; Petrenko, Iu M; Vanin, A F; Stepuro, I I

2010-01-01

The capacity of nitrite, S-nitrosothiols (RS-NO), dinitrosyl iron complexes (DNICs) with thiol-containing ligands, and nitrosoamines to inhibit catalase has been used for the selective determination of these compounds in purely chemical systems and biological liquids: cow milk and colostram. The limiting sensitivity of the method is 50 nM. A comparison of the results of the determinations of RS-NO, DNIC, and nitrite by the catalase method and the Greese method conventionally used for nitrite detection showed that, firstly, Greese reagents decompose DNIC and RS-NO to form nitrite. Therefore, the Greese method cannot be used for nitrite determination in solutions of these substances. Secondly, Greese reagents interact with complexes of mercury ions with RS-NO, inducing the release of nitrosonium ions from the complex followed by the hydrolysis of nitrosonium to nitrite. Thus, the proposition about the spontaneous decay of the complexes of mercury ions with RS-NO is incorrect. Keeping in mind a high sensitivity of the method, the use of catalase as an enzyme detector of nitrosocompounds allows one to detect these compounds in neutral medium without prior purification of the object, thereby preventing artificial effects due to noncontrolled modifications of the compounds under study.

Mixed aqueous solutions as dilution media in the determination of residual solvents by static headspace gas chromatography.

PubMed

D'Autry, Ward; Zheng, Chao; Wolfs, Kris; Yarramraju, Sitaramaraju; Hoogmartens, Jos; Van Schepdael, Ann; Adams, Erwin

2011-06-01

Static headspace (HS) sampling has been commonly used to test for volatile organic chemicals, usually referred to as residual solvents (RS) in pharmaceuticals. If the sample is not soluble in water, organic solvents are used. However, these seriously reduce the sensitivity in the determination of some RS. Here, mixed aqueous dilution media (a mixture of water and an organic solvent like dimethyl formamide, dimethyl sulfoxide or dimethyl acetamide) were studied as alternative media for static HS-gas chromatographic analysis. Although it has been known that mixed aqueous dilution media can often improve sensitivity for many RS, this study used a systematic approach to investigate phase volumes and the organic content in the HS sampling media. Reference solutions using 18 different class 1, 2 and 3 RS were evaluated. The effect of salt addition was also studied in this work. A significant increase in the peak area was observed for all RS using mixed aqueous dilution media, when compared with organic solvents alone. Matrix effects related to the mixed aqueous dilution media were also investigated and reported. Repeatability and linearity obtained with mixed aqueous dilution media were found to be similar to those observed with pure organic solvents. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Response Speed, Contingent Negative Variation and P300 in Alzheimer's Disease and MCI

ERIC Educational Resources Information Center

van Deursen, J. A.; Vuurman, E. F. P. M.; Smits, L. L.; Verhey, F. R. J.; Riedel, W. J.

2009-01-01

Background: Decreased speed of information processing is a hallmark of Alzheimer's disease (AD) and mild cognitive impairment (MCI). Recent studies suggest that response speed (RS) measures are very sensitive indicators of changes in longitudinal follow-up studies. Insight into the psycho-physiological underpinnings of slowed RS can be provided by…

Shrubland primary production and soil respiration diverge along European climate gradient

PubMed Central

Reinsch, Sabine; Koller, Eva; Sowerby, Alwyn; de Dato, Giovanbattista; Estiarte, Marc; Guidolotti, Gabriele; Kovács-Láng, Edit; Kröel-Dulay, György; Lellei-Kovács, Eszter; Larsen, Klaus S.; Liberati, Dario; Peñuelas, Josep; Ransijn, Johannes; Robinson, David A.; Schmidt, Inger K.; Smith, Andrew R.; Tietema, Albert; Dukes, Jeffrey S.; Beier, Claus; Emmett, Bridget A.

2017-01-01

Above- and belowground carbon (C) stores of terrestrial ecosystems are vulnerable to environmental change. Ecosystem C balances in response to environmental changes have been quantified at individual sites, but the magnitudes and directions of these responses along environmental gradients remain uncertain. Here we show the responses of ecosystem C to 8–12 years of experimental drought and night-time warming across an aridity gradient spanning seven European shrublands using indices of C assimilation (aboveground net primary production: aNPP) and soil C efflux (soil respiration: Rs). The changes of aNPP and Rs in response to drought indicated that wet systems had an overall risk of increased loss of C but drier systems did not. Warming had no consistent effect on aNPP across the climate gradient, but suppressed Rs more at the drier sites. Our findings suggest that above- and belowground C fluxes can decouple, and provide no evidence of acclimation to environmental change at a decadal timescale. aNPP and Rs especially differed in their sensitivity to drought and warming, with belowground processes being more sensitive to environmental change. PMID:28256623

Shrubland primary production and soil respiration diverge along European climate gradient

NASA Astrophysics Data System (ADS)

Reinsch, Sabine; Koller, Eva; Sowerby, Alwyn; de Dato, Giovanbattista; Estiarte, Marc; Guidolotti, Gabriele; Kovács-Láng, Edit; Kröel-Dulay, György; Lellei-Kovács, Eszter; Larsen, Klaus S.; Liberati, Dario; Peñuelas, Josep; Ransijn, Johannes; Robinson, David A.; Schmidt, Inger K.; Smith, Andrew R.; Tietema, Albert; Dukes, Jeffrey S.; Beier, Claus; Emmett, Bridget A.

2017-03-01

Above- and belowground carbon (C) stores of terrestrial ecosystems are vulnerable to environmental change. Ecosystem C balances in response to environmental changes have been quantified at individual sites, but the magnitudes and directions of these responses along environmental gradients remain uncertain. Here we show the responses of ecosystem C to 8-12 years of experimental drought and night-time warming across an aridity gradient spanning seven European shrublands using indices of C assimilation (aboveground net primary production: aNPP) and soil C efflux (soil respiration: Rs). The changes of aNPP and Rs in response to drought indicated that wet systems had an overall risk of increased loss of C but drier systems did not. Warming had no consistent effect on aNPP across the climate gradient, but suppressed Rs more at the drier sites. Our findings suggest that above- and belowground C fluxes can decouple, and provide no evidence of acclimation to environmental change at a decadal timescale. aNPP and Rs especially differed in their sensitivity to drought and warming, with belowground processes being more sensitive to environmental change.

Analysis of Sex Hormone Genes Reveals Gender Differences in the Genetic Etiology of Blood Pressure Salt Sensitivity: The GenSalt Study

PubMed Central

2013-01-01

BACKGROUND We examined the association between 799 single-nucleotide polymorphisms in 39 sex hormone genes and blood pressure (BP) responses to a dietary-sodium intervention. METHODS A 7-day low-sodium feeding study (51.3 mmol sodium/day) followed by a 7-day high-sodium feeding study (307.8 mmol sodium/day) was conducted among 1,906 Han Chinese participants. Nine BP measurements were obtained at baseline and the end of each intervention period using a random-zero sphygmomanometer. RESULTS Among men, absolute BP responses to sodium interventions decreased with the number of minor alleles of estrogen receptor 1 (ESR1) markers rs9340844, rs9397453, rs9371562, rs9397459, and rs9383951. For example, mean diastolic blood pressure (DBP) responses to low-sodium intervention (95% confidence interval) were –2.67 (–3.13, –2.22) mm Hg among those with the rs9397453 C/C genotype, –1.23 (–1.98, –0.48) mm Hg among those with the C/T genotype, and 0.08 (–2.31, 2.47) mm Hg among those with the T/T genotype (P = 1×10–4; false discovery rate (FDR)-q = 0.04). Mean DBP responses to high sodium according to the rs9397453 genotypes were 1.46 (1.03, 1.89) mm Hg among those with C/C, 0.19 (–0.54, 0.91) mm Hg among those with C/T, and –1.10 (–2.82, 0.61) mm Hg among those with T/T (P = 2×10–4; FDR-q = 0.04). Similar trends were noted for the association between these ESR1 variants and SBP responses to the dietary intervention. There were no significant associations between sex hormone gene variants and salt sensitivity in women, with genotype-gender interactions noted for the ESR1 markers that achieved significance in men. CONCLUSIONS We identified strong, consistent associations between ESR1 gene variants and salt sensitivity in men. Our results support a gender-specific role for ESR1 in the etiology of this complex trait. PMID:23382403

Laughter as a social rejection cue: gelotophobia and transient cardiac responses to other persons' laughter and insult.

PubMed

Papousek, Ilona; Aydin, Nilüfer; Lackner, Helmut K; Weiss, Elisabeth M; Bühner, Markus; Schulter, Günter; Charlesworth, Canice; Freudenthaler, H Harald

2014-11-01

Other persons' laughter, normally perceived as a signal that persons are friendly and inviting others to approach, can also be perceived as a cue of social rejection. In this study, prerecorded laughter was placed in a realistic and personally relevant context, and participants' responses were related to gelotophobia, a trait predisposing to perceiving laughter as a cue of social rejection. Individuals with gelotophobia showed marked heart rate deceleration in response to the laughter stimulus, possibly indicating a "freezing-like" response. Moreover, cardiac responses to anger provocation by overtly insulting statements indicated heightened aggressive anger in response to cumulated social threat. The study adds to recent research showing specific cardiac responses to social rejection and to the literature on social rejection sensitivity by demonstrating the value of using well interpretable physiological measures in this research context. Copyright © 2014 Society for Psychophysiological Research.

A novel active disturbance rejection based tracking design for laser system with quadrant photodetector

NASA Astrophysics Data System (ADS)

Manojlović, Stojadin M.; Barbarić, Žarko P.; Mitrović, Srđan T.

2015-06-01

A new tracking design for laser systems with different arrangements of a quadrant photodetector, based on the principle of active disturbance rejection control is suggested. The detailed models of quadrant photodetector with standard add-subtract, difference-over-sum and diagonal-difference-over-sum algorithms for displacement signals are included in the control loop. Target moving, non-linearity of a photodetector, parameter perturbations and exterior disturbances are treated as a total disturbance. Active disturbance rejection controllers with linear extended state observers for total disturbance estimation and rejection are designed. Proposed methods are analysed in frequency domain to quantify their stability characteristics and disturbance rejection performances. It is shown through simulations, that tracking errors are effectively compensated, providing the laser spot positioning in the area near the centre of quadrant photodetector where the mentioned algorithms have the highest sensitivity, which provides tracking of the manoeuvring targets with high accuracy.

Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward.

PubMed

Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; Nichols, Weston A; Moaddel, Ruin; Xiao, Cheng; Lester, Henry A

2016-03-09

Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway. Copyright © 2016 the authors 0270-6474/16/362957-18$15.00/0.

Influences of large- and regional-scale climate on fish recruitment in the Skagerrak-Kattegat over the last century

NASA Astrophysics Data System (ADS)

Linderholm, Hans W.; Cardinale, Massimiliano; Bartolino, Valerio; Chen, Deliang; Ou, Tinghai; Svedäng, Henrik

2014-06-01

Dynamics of commercial fish stocks are generally associated with fishing pressure and climate variability. Due to short time series, past studies of the relationships between fish stock dynamics and climate have mainly been restricted to the last few decades. Here we analyzed a century-long time series of plaice, cod and haddock from the Skagerrak-Kattegat, to assess the long-term influence of climate on recruitment. Recruitment success (RS) was compared against sea-surface temperature (SST) and atmospheric circulation indices on large (North Atlantic) and regional (Skagerrak-Kattegat) scales. Our results show that the influence of climate on RS was more pronounced on longer, than on shorter timescales. Over the century-long period, a shift from low to high climate sensitivity was seen from the early to the late part for plaice and cod, while the opposite was found for haddock. This shift suggests that the increasing fishing pressure and the climate change in the Skagerrak-Kattegat have resulted in an increased sensitivity of RS to climate for plaice and cod. The diminishing of climate sensitivity in haddock RS, on the other hand, may be linked to the early twentieth century collapse of the stock in the region. While no long-term relationship between RS and the Atlantic Multidecadal Oscillation (AMO) could be found, large RS fluctuations during the positive phase of the AMO (1935-1960), relative to the cold phases, suggests a changed pattern in recruitment during warm periods. On the other hand, this could be due to the increased fishing pressure in the area. Thus, reported correlations between climate and fish may be caused by strong trends in climate in the late-twentieth century, and coincident reduction in fish stocks caused by intense fishing, rather than a stable relationship between climate and fish recruitment per se.

The influence of oxytocin administration on responses to infant faces and potential moderation by OXTR genotype.

PubMed

Marsh, Abigail A; Yu, Henry H; Pine, Daniel S; Gorodetsky, Elena K; Goldman, David; Blair, R J R

2012-12-01

Oxytocin is a neuropeptide that is associated with increases in social affiliative behaviors, particularly toward infants. However, no previous study has investigated healthy adults' responses to infant faces following oxytocin administration. In addition, given that preliminary evidence suggests that a single-nucleotide polymorphism of the oxytocin receptor (OXTR) gene, rs53576, may influence behaviors associated with parental sensitivity, we assessed whether such responses vary according to OXTR rs53576 genotype. The present study assessed the effects of intranasally administered oxytocin and OXTR genotype on human adults' preferences for infant faces. A double-blind, between-groups design was used, with 57 genotyped volunteers randomly assigned to receive intranasally administered oxytocin or placebo. Fifty minutes following the administration of oxytocin or placebo, participants viewed infants' and adults' faces showing neutral expressions and assessed how appealing they found each face. Infants' faces were more strongly preferred following oxytocin inhalation relative to placebo. When participants were separated according to genotype, this effect was only observed for participants homozygous for the rs53576G allele. Parallel effects were not seen for adults' faces. The present results are consistent with the hypothesis that acute oxytocin administration increases sensitivity to reward-relevant features of infants and/or reduces sensitivity to their aversive properties. The results are also consistent with suggestions of more efficient oxytocinergic function in rs53576G homozygotes.

High resolution melting curve assay for detecting rs12979860 IL28B polymorphisms involved in response of Iranian patients to chronic hepatitis C treatment.

PubMed

Fateh, Abolfazl; Aghasadeghi, Mohammad Reza; Keyvani, Hossein; Mollaie, Hamid Reza; Yari, Shamsi; Hadizade Tasbiti, Ali Reza; Ghazanfari, Morteza; Monavari, Seyed Hamid Reza

2015-01-01

A recent genome-wide association study (GWAS) on patients with chronic hepatitis C (CHC) treated with peginterferon and ribavirin (pegIFN-α/RBV) identified a single nucleotide polymorphism (SNP) on chromosome 19 (rs12979860) which was strongly associated with a sustained virological response (SVR). The aim of this study was twofold: to study the relationship between IL28B rs12979860 and sustained virological response (SVR) to pegIFN-α/RVB therapy among CHC patients and to detect the rs12979860 polymorphism by high resolution melting curve (HRM) assay as a simple, fast, sensitive, and inexpensive method. The study examined outcomes in 100 patients with chronic hepatitis C in 2 provinces of Iran from December 2011 to June 2013. Two methods were applied to detect IL28B polymorphisms: PCR-sequencing as a gold standard method and HRM as a simple, fast, sensitive, and inexpensive method. The frequencies of IL28B rs12979860 CC, CT, and TT alleles in chronic hepatitis C genotype 1a patients were 10% (10/100), 35% (35/100), and 6% (6/100) and in genotype 3a were 13% (13/100), 31% (31/100), and 5% (5/100), respectively. In genotype 3a infected patients, rs12979860 (CC and CT alleles) and in genotype 1a infected patients (CC allele) were significantly associated with a sustained virological response (SVR). The SVR rates for CC, CT and TT (IL28B rs12979860) were 18%, 34% and 4%, respectively. Multiple logistic regression analysis identified two independent factors that were significantly associated with SVR: IL-28B genotype (rs 12979860 CC vs TT and CT; odds ratio [ORs], 7.86 and 4.084, respectively), and HCV subtype 1a (OR, 7.46). In the present study, an association between SVR rates and IL28B polymorphisms was observed. The HRM assay described herein is rapid, inexpensive, sensitive and accurate for detecting rs12979860 alleles in CHC patients. This method can be readily adopted by any molecular diagnostic laboratory with HRM capability and will be clinically beneficial in predicting treatment response in HCV genotype 1 and 3 infected patients. In addition, it was demonstrated that CC and CT alleles in HCV-3a and the CC allele in HCV-1a were significantly associated with response to pegIFN-α/RBV treatment. The present results may help identify subjects for whom the therapy might be successful.

Association of a coding polymorphism in Fc gamma receptor 2A and graft survival in re-transplant candidates.

PubMed

Arnold, Marie-Luise; Fuernrohr, Barbara G; Weiß, Katrin M; Harre, Ulrike; Wiesener, Michael S; Spriewald, Bernd M

2015-10-01

The family of Fc gamma receptors (FcγRs) is involved in mediating immunological effector functions. FcγRs are differentially expressed on immune cells and can act either activating or inhibitory, with FcγR2A belonging to the first group. The polymorphism H131R (rs1801274) in FCGR2A has been associated with acute rejection and can shift the overall balance between activating and inhibitory FcγRs. Anti-HLA allo-antibodies in transplant recipients have been identified as risk factor for organ survival after transplantation. In this study we genotyped FCGR2A H131R in 200 patients who had undergone kidney transplantation and experienced loss of graft function. FCGR2A polymorphism was related to graft survival and anti-HLA antibodies. Graft survival was calculated as the time interval between transplantation and return to chronic dialysis after transplantation. The gene frequency of FCGR2A R/R131 was found significantly more often in patients with earlier (⩽60months) compared to patients with later (>60months) graft failure. Overall patients homozygous for R/R131 had a significantly shorter graft survival, compared to H/H131 or H/R131 which is even more pronounced, when anti-HLA antibodies were present. These data suggest, that FCGR2A polymorphisms constitute a risk factor for graft loss following kidney transplantation and that this effect is related to anti-HLA antibodies. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Role of dorsal hippocampal orexin-1 receptors in memory restoration induced by morphine sensitization phenomenon.

PubMed

Alijanpour, S; Tirgar, F; Zarrindast, M-R

2016-01-15

The present study was examined the blockade of CA1 orexin-1 receptors (OX1Rs) of the dorsal hippocampus in the induction or expression phase on morphine sensitization-induced memory restoration using the Morris water maze (MWM) apparatus. Results showed that pre-training administration of morphine (5mg/kg, s.c.) increases escape latency and traveled distance, while does not alter swimming speed. This supports the impairing effect of morphine on the spatial memory acquisition in male adult rats. Also, in the retrieval session (probe trial) this treatment decreased the time spent in the target quadrant. Moreover, morphine-induced sensitization (15 or 20mg/kg, s.c.; once daily for 3days and followed by 5days no drug treatment) restored the memory acquisition/retrieval deficit which had been induced by pre-training administration of morphine (5mg/kg, s.c.). Intra-CA1 microinjection of subthreshold doses of SB-334867 (OX1Rs antagonist; 10, 20 and 40nmol/rat), 5min before morphine (20mg/kg/day×3days, s.c.; induction phase for morphine sensitization) did not alter restoration of memory acquisition/retrieval produced by the morphine sensitization phenomenon. In contrast, microinjection of subthreshold doses of SB-334867 (10, 20 and 40nmol/rat) into the CA1 region in the training session, 5min prior to morphine (5mg/kg, s.c.; expression phase for morphine sensitization) blocked the spatial memory acquisition/retrieval in morphine-sensitized rats. In conclusion, these findings show that morphine sensitization reverses morphine-induced amnesia. Furthermore, the blockade of CA1 OX1Rs in the expression phase, but not in the induction phase, disrupts memory restoration induced by morphine sensitization. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Sensitivity, Functional Analysis, and Behavior Genetics: A Response to Freeman et al.

ERIC Educational Resources Information Center

Reiss, Steven; Havercamp, Susan M.

1999-01-01

Sensitivity theory divides the causes of challenging behavior into three categories, aberrant contingencies, aberrant environments, and aberrant motivation. This paper replies to criticism that sensitivity theory is circular and unsupported by empirical evidence by reporting on studies that support the theory and rejecting the idea that…

Dark matter sensitivity of multi-ton liquid xenon detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schumann, Marc; Bütikofer, Lukas; Baudis, Laura

2015-10-01

We study the sensitivity of multi ton-scale time projection chambers using a liquid xenon target, e.g., the proposed DARWIN instrument, to spin-independent and spin-dependent WIMP-nucleon scattering interactions. Taking into account realistic backgrounds from the detector itself as well as from neutrinos, we examine the impact of exposure, energy threshold, background rejection efficiency and energy resolution on the dark matter sensitivity. With an exposure of 200 t × y and assuming detector parameters which have been already demonstrated experimentally, spin-independent cross sections as low as 2.5 × 10{sup −49} cm{sup 2} can be probed for WIMP masses around 40 GeV/c{sup 2}. Additional improvementsmore » in terms of background rejection and exposure will further increase the sensitivity, while the ultimate WIMP science reach will be limited by neutrinos scattering coherently off the xenon nuclei.« less

Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study.

PubMed

Thamer, Claus; Machann, Jürgen; Stefan, Norbert; Schäfer, Silke A; Machicao, Fausto; Staiger, Harald; Laakso, Markku; Böttcher, Michael; Claussen, Claus; Schick, Fritz; Fritsche, Andreas; Haring, Hans-Ulrich

2008-04-01

We recently demonstrated that single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-delta gene (PPARD), i.e. rs1053049, rs6902123, and rs2267668, affect the improvement of mitochondrial function, aerobic physical fitness, and insulin sensitivity by lifestyle intervention (LI). The objective of the study was to determine whether the aforementioned PPARD SNPs influence the change in body composition and ectopic fat storage during LI. A total of 156 subjects at an increased risk for type 2 diabetes were genotyped for rs1053049, rs6902123, and rs2267668 and participated in a LI program. Body fat depots, ectopic liver fat, and muscle volume of the leg were quantified using magnetic resonance spectroscopy and imaging. With regard to body composition, carriers of the minor SNP alleles displayed reduced responses to LI, i.e. LI-induced reduction in adipose tissue mass (nonvisceral adipose tissue: rs1053049, P = 0.02; rs2267668, P = 0.04; visceral adipose tissue: rs1053049, P = 0.01) and hepatic lipids (rs1053049, P = 0.04; rs6902123, P = 0.001; independent of changes in adiposity) as well as LI-induced increase in relative muscle volume of the leg (rs1053049, P = 0.003; rs2267668, P = 0.009) were less pronounced in homo- and heterozygous carriers of the minor alleles as compared with homozygous carriers of the major alleles. SNPs rs1053049, rs6902123, and rs2267668 in PPARD affect LI-induced changes in overall adiposity, hepatic fat storage, and relative muscle mass. Our findings provide a mechanistic explanation for the involvement of these genetic variations in the development of insulin resistance and type 2 diabetes.

Culturally sensitive and universal measure of resilience for Japanese populations: Tachikawa Resilience Scale in comparison with Resilience Scale 14-item version.

PubMed

Nishi, Daisuke; Uehara, Ritei; Yoshikawa, Eisho; Sato, Goro; Ito, Masaya; Matsuoka, Yutaka

2013-04-01

Although scales specific to resilience are available and widely used, qualities of resilience could be culturally sensitive. This study aimed to develop a concise scale of resilience for Japanese populations, and compare its validity to that of the Resilience Scale 14-item version (RS-14), one of the most widely used scales for measuring resilience. The Tachikawa Resilience Scale (TRS) was developed on the basis of data obtained from unstructured interviews with Japanese motor vehicle accident survivors without psychiatric disorder. The reliability and validity of the TRS and RS-14 were then examined in cross-sectional studies performed with 523 company workers and 140 psychiatric outpatients. The TRS and RS-14 were negatively correlated with depressive symptoms in company workers and psychiatric outpatients and with anxiety in psychiatric outpatients, and were positively correlated with social support in company workers. Internal consistency and test-retest reliability of the TRS were high. Construct validity of the TRS was equivalent to that of the RS-14 in company workers, and higher than that of the RS-14 in psychiatric outpatients. The reliability and validity of the TRS and RS-14 in Japanese company workers and patients with psychiatric disorders were acceptable. The validity of the TRS was equivalent to or better than that of the RS-14. Although the TRS cannot be regarded as an established scale due to a lack of theoretical rationale, the results of this study suggest that scales measuring resilience that cover cultural aspects might be more relevant in given populations. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke

PubMed Central

Yi, Xingyang; Wang, Yanfen; Zhou, Qiang; Wang, Chun; Cheng, Wen; Chi, Lifen

2016-01-01

Aims: Clopidogrel is an antiplatelet drug primarily used to treat or prevent acute ischemic stroke (IS) or myocardial infarction (MI). This prodrug requires biotransformation to an active metabolite by cytochrome P450 (CYP) enzymes, and CYP single nucleotide polymorphisms (SNPs) could affect the efficiency of such biotransformation. Methods: A total of 375 consecutive IS patients were genotyped for eight CYP SNPs using mass spectrometry. Platelet aggregation activity was measured before and after the 7 – 10 day treatment. Gene–gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients received clopidogrel therapy and were followed up for six months. Primary outcomes were evaluated as a composite of recurrent ischemic stroke (RIS), MI, and death. The secondary outcome was the modified Rankin Scale (mRS). Results: Clopidogrel resistance occurred in 153 patients (40.8%). The frequency of CYP3A5 (rs776746) GG/AG and CYP2C19*2 (rs4244285) AA/AG genotypes was significantly higher in clopidogrel-resistant patients than in sensitive patients. There was a significant gene-gene interaction between CYP3A5 (rs776746) and CYP2C19*2 (rs4244285). CYP2C19*2 AA and its interaction with CYP3A5 GG were independent predictors of clopidogrel resistance and affected the activity of platelet aggregation. Diabetes mellitus, CYP2C19*2 (rs4244285), clopidogrel resistance, and the interaction of CYP2C19*2 with CYP3A5 were all independent risk factors for the primary outcomes of clopidogrel treatment. Clopidogrel-resistant patients were more likely to have poor outcomes (mRS > 2 points) compared with clopidogrel-sensitive patients. Conclusion: CYP SNPs and their interactions are associated with drug resistance and outcomes in acute IS patients. PMID:26961113

Association of human microRNAs miR-22 and miR-491 polymorphisms with panic disorder with or without agoraphobia in a Korean population.

PubMed

Kim, Borah; Kim, Min Kyoung; Kim, Se-Woong; Kim, Kyoung-Min; Kim, Hyun Seok; An, Hui Jeong; Kim, Jung O; Choi, Tai Kiu; Kim, Nam Keun; Lee, Sang-Hyuk

2015-12-01

The possible involvement of microRNAs (miRNA) in psychiatric disorders has been recently recognized. Several miRNA polymorphisms have been found to be associated with panic disorder (PD) in European populations. However, the association of miRNA polymorphisms on PD has not been reported in Asian populations. We evaluated the effect of miR-22 and miR-491 polymorphisms on susceptibility to PD in a Korean population. Genotyping for four polymorphic variants of the primary miRNA (pri-miRNA) regions of miR-22 (rs8076112 and rs6502892) and miR-491 (rs4977831 and rs2039391) was performed using blood samples of 341 Korean patients with PD and 229 healthy control subjects. To evaluate PD phenotypes, the Panic Disorder Severity Scale (PDSS) and Anxiety Sensitivity Inventory-Revised (ASI-R) were administered. Three single-nucleotide polymorphisms (SNPs) were found to be associated with PD: rs8076112 miR-22 and rs4977831 and miR-491 rs2039391. The rs8076112C/rs6502892C haplotypes of miR-22 and rs4977831G/rs2039391G and rs4977831A/rs2039391A haplotypes of miR-491 were significantly overrepresented in patients with PD than in healthy control subjects. In combination analysis, miR-22 rs8076112AC/rs6502892CC and rs8076112CC/rs6502892CC and miR-491 rs4977831AG/rs2039391AA were more frequent in patients with PD. Among the phenotype assessments, ASI-R scores were significantly associated with miR-22 rs6502892 in the subgroup with the agoraphobic phenotype. The results should be considered preliminary due to the relatively small sample size and the selection of only four SNPs. This is the first report to show possible associations of miR-22 and miR-491 with genetic susceptibility to PD in a Korean population. Copyright © 2015 Elsevier B.V. All rights reserved.

Applying Cost-Sensitive Extreme Learning Machine and Dissimilarity Integration to Gene Expression Data Classification.

PubMed

Liu, Yanqiu; Lu, Huijuan; Yan, Ke; Xia, Haixia; An, Chunlin

2016-01-01

Embedding cost-sensitive factors into the classifiers increases the classification stability and reduces the classification costs for classifying high-scale, redundant, and imbalanced datasets, such as the gene expression data. In this study, we extend our previous work, that is, Dissimilar ELM (D-ELM), by introducing misclassification costs into the classifier. We name the proposed algorithm as the cost-sensitive D-ELM (CS-D-ELM). Furthermore, we embed rejection cost into the CS-D-ELM to increase the classification stability of the proposed algorithm. Experimental results show that the rejection cost embedded CS-D-ELM algorithm effectively reduces the average and overall cost of the classification process, while the classification accuracy still remains competitive. The proposed method can be extended to classification problems of other redundant and imbalanced data.

Insulin-sensitizing effects on muscle and adipose tissue after dietary fiber intake in men and women with metabolic syndrome.

PubMed

Robertson, M Denise; Wright, John W; Loizon, Emmanuelle; Debard, Cyrille; Vidal, Hubert; Shojaee-Moradie, Fariba; Russell-Jones, David; Umpleby, A Margot

2012-09-01

Dietary fibers have been associated with a reduced incidence of type 2 diabetes mellitus in epidemiological studies; however, the precise mechanisms are unknown. The objective of the study was to evaluate the efficacy and site of action of an insoluble dietary fiber derived from maize (HAM-RS2) in improving insulin resistance in subjects at increased risk of type 2 diabetes mellitus. This study was a randomized, controlled crossover, dietary intervention study. The study was conducted at the Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Fifteen men and women with insulin resistance participated in the study. The intervention included 40 g/d HAM-RS2 compared with a matched placebo for 8 wk. After each supplement, participants underwent a two-step hyperinsulinemic-euglycemic clamp study with the addition of glucose tracers; a meal tolerance test; arteriovenous sampling across forearm muscle tissue; and a sc adipose tissue biopsy for assessment of gene expression. There was enhanced uptake of glucose into the forearm muscle measured by arteriovenous sampling (65 ± 15% increase after resistant starch; P < 0.001). Adipose tissue function was also affected, with enhanced fatty acid suppression after HAM-RS2 treatment and an increase in gene expression for hormone sensitive lipase (P = 0.005), perilipin (P = 0.011), lipoprotein lipase (P = 0.014), and adipose triglyceride lipase (P = 0.03) in biopsy samples. There was no effect on the insulin sensitivity of hepatic glucose production or plasma lipids after HAM-RS2. HAM-RS2 improved peripheral but not hepatic insulin resistance and requires further study as an intervention in patients with or at risk for type 2 diabetes.

Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

PubMed Central

Gustafsson, Stefan; Rybin, Denis; Stančáková, Alena; Chen, Han; Liu, Ching-Ti; Hong, Jaeyoung; Jensen, Richard A.; Rice, Ken; Morris, Andrew P.; Mägi, Reedik; Tönjes, Anke; Prokopenko, Inga; Kleber, Marcus E.; Delgado, Graciela; Silbernagel, Günther; Jackson, Anne U.; Appel, Emil V.; Grarup, Niels; Lewis, Joshua P.; Montasser, May E.; Landenvall, Claes; Staiger, Harald; Luan, Jian’an; Frayling, Timothy M.; Weedon, Michael N.; Xie, Weijia; Morcillo, Sonsoles; Martínez-Larrad, María Teresa; Biggs, Mary L.; Chen, Yii-Der Ida; Corbaton-Anchuelo, Arturo; Færch, Kristine; Gómez-Zumaquero, Juan Miguel; Goodarzi, Mark O.; Kizer, Jorge R.; Koistinen, Heikki A.; Leong, Aaron; Lind, Lars; Lindgren, Cecilia; Machicao, Fausto; Manning, Alisa K.; Martín-Núñez, Gracia María; Rojo-Martínez, Gemma; Rotter, Jerome I.; Siscovick, David S.; Zmuda, Joseph M.; Zhang, Zhongyang; Serrano-Rios, Manuel; Smith, Ulf; Soriguer, Federico; Hansen, Torben; Jørgensen, Torben J.; Linnenberg, Allan; Pedersen, Oluf; Walker, Mark; Langenberg, Claudia; Scott, Robert A.; Wareham, Nicholas J.; Fritsche, Andreas; Häring, Hans-Ulrich; Stefan, Norbert; Groop, Leif; O’Connell, Jeff R.; Boehnke, Michael; Bergman, Richard N.; Collins, Francis S.; Mohlke, Karen L.; Tuomilehto, Jaakko; März, Winfried; Kovacs, Peter; Stumvoll, Michael; Psaty, Bruce M.; Kuusisto, Johanna; Laakso, Markku; Meigs, James B.; Dupuis, Josée; Ingelsson, Erik; Florez, Jose C.

2016-01-01

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10−11), rs12454712 (BCL2; P = 2.7 × 10−8), and rs10506418 (FAM19A2; P = 1.9 × 10−8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci. PMID:27416945

Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study.

PubMed

Zapf, Antonia; Gwinner, Wilfried; Karch, Annika; Metzger, Jochen; Haller, Hermann; Koch, Armin

2015-09-15

Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect acute rejections. This study determines the diagnostic performance of the test in the routine setting of post-transplant patient care, compared to the biopsy-based rejection diagnosis. The next step would be a randomized trial to compare the two diagnostic strategies (including the urine test or not) in relation to patient relevant endpoints. NCT01315067 ; March 14, 2011.

Anti-Armor, Confined Space, Reduced Sensitivity (AT4CS-RS) Insensitive Munitions (IM) Effort: Summary and Conclusions

DTIC Science & Technology

An effort was initiated to develop an insensitive munitions packaging solution for the AT4CS-RS.The effort investigated several promising designs...Initial engineering testing showed that the most promising design is the deflection plate concept, which will achieve a type IV reaction for Slow Cook

Prevalence Estimation and Validation of New Instruments in Psychiatric Research: An Application of Latent Class Analysis and Sensitivity Analysis

ERIC Educational Resources Information Center

Pence, Brian Wells; Miller, William C.; Gaynes, Bradley N.

2009-01-01

Prevalence and validation studies rely on imperfect reference standard (RS) diagnostic instruments that can bias prevalence and test characteristic estimates. The authors illustrate 2 methods to account for RS misclassification. Latent class analysis (LCA) combines information from multiple imperfect measures of an unmeasurable latent condition to…

Parasitic egg rejection decisions of chalk-browed mockingbirds Mimus saturninus are independent of clutch composition.

PubMed

de la Colina, M A; Pompilio, L; Hauber, M E; Reboreda, J C; Mahler, B

2018-03-01

Obligate avian brood parasites lay their eggs in nests of other host species, which assume all the costs of parental care for the foreign eggs and chicks. The most common defensive response to parasitism is the rejection of foreign eggs by hosts. Different cognitive mechanisms and decision-making rules may guide both egg recognition and rejection behaviors. Classical optimization models generally assume that decisions are based on the absolute properties of the options (i.e., absolute valuation). Increasing evidence shows instead that hosts' rejection decisions also depend on the context in which options are presented (i.e., context-dependent valuation). Here we study whether the chalk-browed mockingbird's (Mimus saturninus) rejection of parasitic shiny cowbird (Molothrus bonariensis) eggs is a fixed behavior or varies with the context of the clutch. We tested three possible context-dependent mechanisms: (1) range effect, (2) habituation to variation, and (3) sensitization to variation. We found that mockingbird rejection of parasitic eggs does not change according to the characteristics of the other eggs in the nest. Thus, rejection decisions may exclusively depend on the objective characteristics of the eggs, meaning that the threshold of acceptance or rejection of a foreign egg is context-independent in this system.

The relation between schizotypy and early attention to rejecting interactions: The influence of neuroticism

PubMed Central

Premkumar, Preethi; Onwumere, Juliana; Albert, Jacobo; Kessel, Dominique; Kumari, Veena; Kuipers, Elizabeth; Carretié, Luis

2015-01-01

Abstract Objectives: Schizotypy relates to rejection sensitivity (anxiety reflecting an expectancy of social exclusion) and neuroticism (excessive evaluation of negative emotions). Positive schizotypy (e.g., perceptual aberrations and odd beliefs) and negative schizotypy (e.g., social and physical anhedonia) could relate to altered attention to rejection because of neuroticism. Methods: Forty-one healthy individuals were assessed on positive and negative schizotypy and neuroticism, and event-related potentials during rejecting, accepting and neutral scenes. Participants were categorised into high, moderate and low neuroticism groups. Using temporo-spatial principal components analyses, P200 (peak latency =290 ms) and P300 amplitudes (peak latency = 390 ms) were measured, reflecting mobilisation of attention and early attention, respectively. Results: Scalp-level and cortical source analysis revealed elevated fronto-parietal N300/P300 amplitude and P200-related dorsal anterior cingulate current density during rejection than acceptance/neutral scenes. Positive schizotypy related inversely to parietal P200 amplitude during rejection. Negative schizotypy related positively to P200 middle occipital current density. Negative schizotypy related positively to parietal P300, where the association was stronger in high and moderate, than low, neuroticism groups. Conclusions: Positive and negative schizotypy relate divergently to attention to rejection. Positive schizotypy attenuates, but negative schizotypy increases rejection-related mobilisation of attention. Negative schizotypy increases early attention to rejection partly due to elevated neuroticism. PMID:26452584

Membrane-Based Water Evaporator for a Space Suit

NASA Technical Reports Server (NTRS)

Ungar, Eugene K.; McCann, Charles J.; O'Connell, Mary K.; Andrea, Scott

2004-01-01

A membrane-based water evaporator has been developed that is intended to serve as a heat-rejection device for a space suit. This evaporator would replace the current sublimator that is sensitive to contamination of its feedwater. The design of the membrane-based evaporator takes advantage of recent advances in hydrophobic micropore membranes to provide robust heat rejection with much less sensitivity to contamination. The low contamination sensitivity allows use of the heat transport loop as feedwater, eliminating the need for the separate feedwater system used for the sublimator. A cross section of the evaporator is shown in the accompanying figure. The space-suit cooling loop water flows into a distribution plenum, through a narrow annulus lined on both sides with a hydrophobic membrane, into an exit plenum, and returns to the space suit. Two perforated metal tubes encase the membranes and provide structural strength. Evaporation at the membrane inner surface dissipates the waste heat from the space suit. The water vapor passes through the membrane, into a steam duct and is vented to the vacuum environment through a back-pressure valve. The back-pressure setting can be adjusted to regulate the heat-rejection rate and the water outlet temperature.

Time spent with friends in adolescence relates to less neural sensitivity to later peer rejection.

PubMed

Masten, Carrie L; Telzer, Eva H; Fuligni, Andrew J; Lieberman, Matthew D; Eisenberger, Naomi I

2012-01-01

Involvement with friends carries many advantages for adolescents, including protection from the detrimental effects of being rejected by peers. However, little is known about the mechanisms through which friendships may serve their protective role at this age, or the potential benefit of these friendships as adolescents transition to adulthood. As such, this investigation tested whether friend involvement during adolescence related to less neural sensitivity to social threats during young adulthood. Twenty-one adolescents reported the amount of time they spent with friends outside of school using a daily diary. Two years later they underwent an fMRI scan, during which they were ostensibly excluded from an online ball-tossing game by two same-age peers. Findings from region of interest and whole brain analyses revealed that spending more time with friends during adolescence related to less activity in the dorsal anterior cingulate cortex and anterior insula--regions previously linked with negative affect and pain processing--during an experience of peer rejection 2 years later. These findings are consistent with the notion that positive relationships during adolescence may relate to individuals being less sensitive to negative social experiences later on.

The relationship between experiences of discrimination and mental health among lesbians and gay men: An examination of internalized homonegativity and rejection sensitivity as potential mechanisms.

PubMed

Feinstein, Brian A; Goldfried, Marvin R; Davila, Joanne

2012-10-01

The current study used path analysis to examine potential mechanisms through which experiences of discrimination influence depressive and social anxiety symptoms. The sample included 218 lesbians and 249 gay men (total N = 467) who participated in an online survey about minority stress and mental health. The proposed model included 2 potential mediators-internalized homonegativity and rejection sensitivity-as well as a culturally relevant antecedent to experiences of discrimination-childhood gender nonconformity. Results indicated that the data fit the model well, supporting the mediating roles of internalized homonegativity and rejection sensitivity in the associations between experiences of discrimination and symptoms of depression and social anxiety. Results also supported the role of childhood gender nonconformity as an antecedent to experiences of discrimination. Although there were not significant gender differences in the overall model fit, some of the associations within the model were significantly stronger for gay men than lesbians. These findings suggest potential mechanisms through which experiences of discrimination influence well-being among sexual minorities, which has important implications for research and clinical practice with these populations. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

The emerging role of the FKBP5 gene polymorphisms in vulnerability-stress model of schizophrenia: further evidence from a Serbian population.

PubMed

Mihaljevic, Marina; Zeljic, Katarina; Soldatovic, Ivan; Andric, Sanja; Mirjanic, Tijana; Richards, Alexander; Mantripragada, Kiran; Pekmezovic, Tatjana; Novakovic, Ivana; Maric, Nadja P

2017-09-01

Increased reactivity to stress is observed in patients with schizophrenia spectrum disorders and their healthy siblings in comparison with the general population. Additionally, higher levels of neuroticism, as a proposed psychological measure of stress sensitivity, increase the risk of schizophrenia. HPA axis dysregulation is one of the possible mechanisms related to the vulnerability-stress model of schizophrenia, and recent studies revealed a possible role of the functional genetic variants of FK506-binding protein 51 (FKBP5) gene which modulate activity of HPA axis. The purpose of the present study was to investigate impact of FKBP5 on schizophrenia in Serbian patients and to explore relationship between genetic variants and neuroticism by using the case-sibling-control design. In 158 subjects, we measured psychotic experiences, childhood trauma and neuroticism. Nine single-nucleotide polymorphisms (rs9295158, rs3800373, rs9740080, rs737054, rs6926133, rs9380529, rs9394314, rs2766533 and rs12200498) were genotyped. The genetic influence was modeled using logistic regression, and the relationship between genetic variants and neuroticism was assessed by linear mixed model. Our results revealed genetic main effect of FKBP5 risk alleles (A allele of rs9296158 and T allele of rs3800373) and AGTC "risk" haplotype combination (rs9296158, rs3800373, rs9470080 and rs737054, respectively) on schizophrenia, particularly when childhood trauma was set as a confounding factor. We confirmed strong relationship between neuroticism and psychotic experiences in patients and siblings and further showed relationship between higher levels of neuroticism and FKBP5 risk variants suggesting potential link between biological and psychosocial risk factors. Our data support previous findings that trauma exposure shapes FKBP5 impact on schizophrenia.

Meta-analysis of the rs2075650 polymorphism and risk of Alzheimer disease.

PubMed

He, Ya; Li, Chen; Yang, Ying; Li, Yizhou; Wang, Yuan; Yang, Hua; Jin, Tianbo; Chen, Songsheng

2016-10-01

Several researchers have suggested that the rs2075650 polymorphism is significantly associated with an increased risk of developing Alzheimer disease (AD) in European. However, some others found inconsistent results in Asian (Chinese and Korean). We addressed the controversy through performing a meta-analysis of the relationship between rs2075650 in TOMM40 (translocase of outer mitochondrial membrane 40 homologue) and Alzheimer disease. We selected eight case-control studies involving 4290 cases of Alzheimer disease and 5556 healthy individuals. The association between the TOMM40 rs2075650 polymorphism and Alzheimer disease was examined by overall odds ratio (OR) with a 95 % confidence interval (CI). We used different genetic model analysis, sensitivity analysis, and assessments of bias in our meta-analysis. The pooled analysis showed the inconsistent results that TOMM40 rs2075650 polymorphism was associated with Alzheimer disease in European and Korean population in all genetic models, but there was no significant association between the TOMM40 rs2075650 polymorphism and Alzheimer disease risk in Chinese population. We conclude that rs2075650 in TOMM40 gene may increase the risk of Alzheimer disease.

Antifungal activity of essential oils on two Venturia inaequalis strains with different sensitivities to tebuconazole.

PubMed

Muchembled, Jérôme; Deweer, Caroline; Sahmer, Karin; Halama, Patrice

2017-11-02

The antifungal activity of seven essential oils (eucalyptus, clove, mint, oregano, savory, tea tree, and thyme) was studied on Venturia inaequalis, the fungus responsible for apple scab. The composition of the essential oils was checked by gas chromatography-mass spectrometry. Each essential oil had its main compound. Liquid tests were performed to calculate the IC 50 of essential oils as well as their majority compounds. The tests were made on two strains with different sensitivities to tebuconazole: S755, the sensitive strain, and rs552, the strain with reduced sensitivity. Copper sulfate was selected as the reference mineral fungicidal substance. IC 50 with confidence intervals were calculated after three independent experiments. The results showed that all essential oils and all major compounds had in vitro antifungal activities. Moreover, it was highlighted that the effectiveness of four essential oils (clove, eucalyptus, mint, and savory) was higher than copper sulfate on both strains. For each strain, the best activity was obtained using clove and eucalyptus essential oils. For clove, the IC 50 obtained on the sensitive strain (5.2 mg/L [4.0-6.7 mg/L]) was statistically lower than the IC 50 of reduced sensitivity strain (14 mg/L [11.1-17.5 mg/L]). In contrast, for eucalyptus essential oil, the IC 50 were not different with respectively 9.4-13.0 and 12.2-17.9 mg/L for S755 and rs552 strains. For mint, origano, savory, tea tree, and thyme, IC 50 were always the best on rs552 strain. The majority compounds were not necessarily more efficient than their corresponding oils; only eugenol (for clove) and carvacrol (for oregano and savory) seemed to be more effective on S755 strain. On the other hand, rs552 strain seemed to be more sensitive to essential oils than S755 strain. In overall, it was shown that essential oils have different antifungal activities but do not have the same antifungal activities depending on the fungus strain used.

Dynamical response of the Galileo Galilei on the ground rotor to test the equivalence principle: Theory, simulation, and experiment. II. The rejection of common mode forces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Comandi, G.L.; Toncelli, R.; Chiofalo, M.L.

'Galileo Galilei on the ground' (GGG) is a fast rotating differential accelerometer designed to test the equivalence principle (EP). Its sensitivity to differential effects, such as the effect of an EP violation, depends crucially on the capability of the accelerometer to reject all effects acting in common mode. By applying the theoretical and simulation methods reported in Part I of this work, and tested therein against experimental data, we predict the occurrence of an enhanced common mode rejection of the GGG accelerometer. We demonstrate that the best rejection of common mode disturbances can be tuned in a controlled way bymore » varying the spin frequency of the GGG rotor.« less

A computational pipeline for the development of multi-marker bio-signature panels and ensemble classifiers

PubMed Central

2012-01-01

Background Biomarker panels derived separately from genomic and proteomic data and with a variety of computational methods have demonstrated promising classification performance in various diseases. An open question is how to create effective proteo-genomic panels. The framework of ensemble classifiers has been applied successfully in various analytical domains to combine classifiers so that the performance of the ensemble exceeds the performance of individual classifiers. Using blood-based diagnosis of acute renal allograft rejection as a case study, we address the following question in this paper: Can acute rejection classification performance be improved by combining individual genomic and proteomic classifiers in an ensemble? Results The first part of the paper presents a computational biomarker development pipeline for genomic and proteomic data. The pipeline begins with data acquisition (e.g., from bio-samples to microarray data), quality control, statistical analysis and mining of the data, and finally various forms of validation. The pipeline ensures that the various classifiers to be combined later in an ensemble are diverse and adequate for clinical use. Five mRNA genomic and five proteomic classifiers were developed independently using single time-point blood samples from 11 acute-rejection and 22 non-rejection renal transplant patients. The second part of the paper examines five ensembles ranging in size from two to 10 individual classifiers. Performance of ensembles is characterized by area under the curve (AUC), sensitivity, and specificity, as derived from the probability of acute rejection for individual classifiers in the ensemble in combination with one of two aggregation methods: (1) Average Probability or (2) Vote Threshold. One ensemble demonstrated superior performance and was able to improve sensitivity and AUC beyond the best values observed for any of the individual classifiers in the ensemble, while staying within the range of observed specificity. The Vote Threshold aggregation method achieved improved sensitivity for all 5 ensembles, but typically at the cost of decreased specificity. Conclusion Proteo-genomic biomarker ensemble classifiers show promise in the diagnosis of acute renal allograft rejection and can improve classification performance beyond that of individual genomic or proteomic classifiers alone. Validation of our results in an international multicenter study is currently underway. PMID:23216969

A computational pipeline for the development of multi-marker bio-signature panels and ensemble classifiers.

PubMed

Günther, Oliver P; Chen, Virginia; Freue, Gabriela Cohen; Balshaw, Robert F; Tebbutt, Scott J; Hollander, Zsuzsanna; Takhar, Mandeep; McMaster, W Robert; McManus, Bruce M; Keown, Paul A; Ng, Raymond T

2012-12-08

Biomarker panels derived separately from genomic and proteomic data and with a variety of computational methods have demonstrated promising classification performance in various diseases. An open question is how to create effective proteo-genomic panels. The framework of ensemble classifiers has been applied successfully in various analytical domains to combine classifiers so that the performance of the ensemble exceeds the performance of individual classifiers. Using blood-based diagnosis of acute renal allograft rejection as a case study, we address the following question in this paper: Can acute rejection classification performance be improved by combining individual genomic and proteomic classifiers in an ensemble? The first part of the paper presents a computational biomarker development pipeline for genomic and proteomic data. The pipeline begins with data acquisition (e.g., from bio-samples to microarray data), quality control, statistical analysis and mining of the data, and finally various forms of validation. The pipeline ensures that the various classifiers to be combined later in an ensemble are diverse and adequate for clinical use. Five mRNA genomic and five proteomic classifiers were developed independently using single time-point blood samples from 11 acute-rejection and 22 non-rejection renal transplant patients. The second part of the paper examines five ensembles ranging in size from two to 10 individual classifiers. Performance of ensembles is characterized by area under the curve (AUC), sensitivity, and specificity, as derived from the probability of acute rejection for individual classifiers in the ensemble in combination with one of two aggregation methods: (1) Average Probability or (2) Vote Threshold. One ensemble demonstrated superior performance and was able to improve sensitivity and AUC beyond the best values observed for any of the individual classifiers in the ensemble, while staying within the range of observed specificity. The Vote Threshold aggregation method achieved improved sensitivity for all 5 ensembles, but typically at the cost of decreased specificity. Proteo-genomic biomarker ensemble classifiers show promise in the diagnosis of acute renal allograft rejection and can improve classification performance beyond that of individual genomic or proteomic classifiers alone. Validation of our results in an international multicenter study is currently underway.

Adolescent peer-rejection persistently alters pain perception and CB1 receptor expression in female rats.

PubMed

Schneider, Peggy; Hannusch, Christin; Schmahl, Christian; Bohus, Martin; Spanagel, Rainer; Schneider, Miriam

2014-02-01

Peer-interactions are particularly important during adolescence and teenagers display enhanced sensitivity toward rejection by peers. Social rejection has been shown to induce alterations in pain perception in humans. However, the neurobiological consequences of adolescent social rejection have yet to be extensively characterized, and no appropriate animal model is available. Here, we propose inadequate playful interactions in adolescent rats as a novel animal model for social peer-rejection and examine potential long-term consequences into adulthood. Acute social pairing of female adolescent Wistar rats with an age-matched rat from the less playful Fischer344 strain was found to alter social play and decrease pain reactivity, indicating Fischer rats as inadequate social partners for Wistar animals. Therefore, in a second experiment, adolescent female Wistar rats were either reared with another Wistar rat (adequate social rearing; control) or with a Fischer rat (inadequate social rearing; play-deprived). Beginning on day 50, all Wistar rats were group housed with same-strain partners and tested for behavioral, neurobiological and endocrine differences in adulthood. Playful peer-interactions were decreased during adolescence in play-deprived animals, without affecting social contact behavior. Consequently, adult play-deprived rats showed decreased pain sensitivity and increased startle reactivity compared to controls, but did not differ in activity, anxiety-related behavior or social interaction. Both groups also differed in their endocrine stress-response, and expression levels of the cannabinoid CB1 receptor were increased in the thalamus, whereas FAAH levels were decreased in the amygdala. The present animal model therefore represents a novel approach to assess the long-term consequences of peer-rejection during adolescence. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.

PubMed

Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

2014-11-01

To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dzhugashvili, Maia; Department of Radiation Oncology, Madrid Oncology Institute; Luengo-Gil, Ginés

Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95%more » confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.« less

Quantification of soil respiration in forest ecosystems across China

NASA Astrophysics Data System (ADS)

Song, Xinzhang; Peng, Changhui; Zhao, Zhengyong; Zhang, Zhiting; Guo, Baohua; Wang, Weifeng; Jiang, Hong; Zhu, Qiuan

2014-09-01

We collected 139 estimates of the annual forest soil CO2 flux and 173 estimates of the Q10 value (the temperature sensitivity) assembled from 90 published studies across Chinese forest ecosystems. We analyzed the annual soil respiration (Rs) rates and the temperature sensitivities of seven forest ecosystems, including evergreen broadleaf forests (EBF), deciduous broadleaf forests (DBF), broadleaf and needleleaf mixed forests (BNMF), evergreen needleleaf forests (ENF), deciduous needleleaf forests (DNF), bamboo forests (BF) and shrubs (SF). The results showed that the mean annual Rs rate was 33.65 t CO2 ha-1 year-1 across Chinese forest ecosystems. Rs rates were significantly different (P < 0.001) among the seven forest types, and were significantly and positively influenced by mean annual temperature (MAT), mean annual precipitation (MAP), and actual evapotranspiration (AET); but negatively affected by latitude and elevation. The mean Q10 value of 1.28 was lower than the world average (1.4-2.0). The Q10 values derived from the soil temperature at a depth of 5 cm varied among forest ecosystems by an average of 2.46 and significantly decreased with the MAT but increased with elevation and latitude. Moreover, our results suggested that an artificial neural network (ANN) model can effectively predict Rs across Chinese forest ecosystems. This study contributes to better understanding of Rs across Chinese forest ecosystems and their possible responses to global warming.

The allosteric site regulates the voltage sensitivity of muscarinic receptors.

PubMed

Hoppe, Anika; Marti-Solano, Maria; Drabek, Matthäus; Bünemann, Moritz; Kolb, Peter; Rinne, Andreas

2018-01-01

Muscarinic receptors (M-Rs) for acetylcholine (ACh) belong to the class A of G protein-coupled receptors. M-Rs are activated by orthosteric agonists that bind to a specific site buried in the M-R transmembrane helix bundle. In the active conformation, receptor function can be modulated either by allosteric modulators, which bind to the extracellular receptor surface or by the membrane potential via an unknown mechanism. Here, we compared the modulation of M 1 -Rs and M 3 -Rs induced by changes in voltage to their allosteric modulation by chemical compounds. We quantified changes in receptor signaling in single HEK 293 cells with a FRET biosensor for the G q protein cycle. In the presence of ACh, M 1 -R signaling was potentiated by voltage, similarly to positive allosteric modulation by benzyl quinolone carboxylic acid. Conversely, signaling of M 3 -R was attenuated by voltage or the negative allosteric modulator gallamine. Because the orthosteric site is highly conserved among M-Rs, but allosteric sites vary, we constructed "allosteric site" M 3 /M 1 -R chimeras and analyzed their voltage dependencies. Exchanging the entire allosteric sites eliminated the voltage sensitivity of ACh responses for both receptors, but did not affect their modulation by allosteric compounds. Furthermore, a point mutation in M 3 -Rs caused functional uncoupling of the allosteric and orthosteric sites and abolished voltage dependence. Molecular dynamics simulations of the receptor variants indicated a subtype-specific crosstalk between both sites, involving the conserved tyrosine lid structure of the orthosteric site. This molecular crosstalk leads to receptor subtype-specific voltage effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Implicit Association to Infant Faces: How Genetics, Early Care Experiences, and Cultural Factors Influence Caregiving Propensities

PubMed Central

Senese, Vincenzo Paolo; Shinohara, Kazuyuki; Esposito, Gianluca; Doi, Hirokazu; Venuti, Paola; Bornstein, Marc H.

2018-01-01

Genetics, early experience, and culture shape caregiving, but it is still not clear how genetics, early experiences, and cultural factors might interact to influence specific caregiving propensities, such as adult responsiveness to infant cues. To address this gap, 80 Italian adults (50% M; 18-25 years) were (1) genotyped for two oxytocin receptor gene polymorphisms (rs53576 and rs2254298) and the serotonin transporter gene polymorphism (5-HTTLPR), which are implicated in parenting behaviour, (2) completed the Adult Parental Acceptance/Rejection Questionnaire to evaluate their recollections of parental behaviours toward them in childhood, and (3) were administered a Single Category Implicit Association Test to evaluate their implicit responses to faces of Italian infants, Japanese infants, and Italian adults. Analysis of implicit associations revealed that Italian infant faces were evaluated as most positive; participants in the rs53576 GG group had the most positive implicit associations to Italian infant faces; the serotonin polymorphism moderated the effect of early care experiences on adults’ implicit association to both Italian infant and adult female faces. Finally, 5-HTTLPR S carriers showed less positive implicit responses to Japanese infant faces. We conclude that adult in-group preference extends to in-group infant faces and that implicit responses to social cues are influenced by interactions of genetics, early care experiences, and cultural factors. These findings have implications for understanding processes that regulate adult caregiving. PMID:27650102

Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains site

DOE PAGES

Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri; ...

2016-07-20

In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 andmore » RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. In addition, these results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.« less

How the creative use of analogies can shape medical practice.

PubMed

Prasad, G V Ramesh

2015-06-01

Analogical reasoning is central to medical progress, and is either creative or conservative. According to Hofmann et al., conservative analogy relates concepts from old technology to new technologies with emphasis on preservation of comprehension and conduct. Creative analogy however brings new understanding to new technology, brings similarities existing in the source domain to a target domain where they previously had no bearing, and imports something entirely different from the content of the analogy itself. I defend the claim that while conservative analogies are useful by virtue of being comfortable to use from familiarity and experience, and are more easily accepted by society, they only lead to incremental advances in medicine. However, creative analogies are more exciting and productive because they generate previously unexpected associations across widely separated domains, emphasize relations over physical similarities, and structure over superficiality. I use kidney transplantation and anti-rejection medication development as an exemplar of analogical reasoning used to improve medical practice. Anti-rejection medication has not helped highly sensitized patients because of their propensity to rejecting most organs. I outline how conservative analogical reasoning led to anti-rejection medication development, but creative analogical reasoning helped highly sensitized and blood type incompatible patients through domino transplants, by which they obtain a kidney to which they are not sensitized. Creative analogical reasoning is more likely than conservative analogical reasoning to lead to revolutionary progress. While these analogies overlap and creative analogies eventually become conservative, progress is best facilitated by combining conservative and creative analogical reasoning. © 2015 John Wiley & Sons, Ltd.

Estradiol Variability, Stressful Life Events and the Emergence of Depressive Symptomatology during the Menopause Transition

PubMed Central

Gordon, Jennifer L.; Rubinow, David R.; Eisenlohr-Moul, Tory A; Leserman, Jane; Girdler, Susan S.

2015-01-01

Objective To examine the role of estradiol fluctuation in triggering depressive symptoms in the menopause transition and assess the role of recent very stressful life events (VSLEs) as a moderating factor in this relationship. Methods 52 euthymic women in the menopause transition or early postmenopause (age 45–60) who were assigned to the placebo arm of a randomized controlled trial of hormone therapy provided the data for this report. At enrollment, women’s experience of recent VSLEs, depressive symptoms, serum estradiol and progesterone were assessed. At months 1, 8 and 14, depressive symptoms and hormones were re-assessed and participants underwent a stressor battery involving a speech and a mental arithmetic task. Participants rated their feelings of anxiety, fear, anger and rejection. The standard deviation of estradiol provided an index of hormone variability over the entire 14 months. Results Greater estradiol variability across the 14 months predicted greater depressive symptoms at month 14, though only in women reporting a higher number of VSLEs at baseline (39% of women reported ≤1 recent event). Greater estradiol variability also predicted greater feelings of rejection to the laboratory stressor at months 8 and 14. Furthermore, among women reporting higher VSLEs at baseline, feelings of rejection in response to the laboratory stressor at month 8 predicted depressive symptoms at month 14. Conclusion These data suggest estradiol variability may enhance emotional sensitivity to psychosocial stress, particularly sensitivity to social rejection. Combined with VSLEs proximate to the menopause transition, this increased sensitivity may contribute to the development of depressed mood. PMID:26529616

[Sequential monitoring of renal transplant with aspiration cytology].

PubMed

Manfro, R C; Gonçalves, L F; de Moura, L A

1998-01-01

To evaluate the utility of kidney aspiration cytology in the sequential monitorization of acute rejection in renal transplant patients. Thirty patients were submitted to 376 aspirations. The clinical diagnoses were independently established. The representativity of the samples reached 82.7%. The total corrected increment index and the number of immunoactivated cells were higher during acute rejection as compared to normal allograft function, acute tubular necrosis, and cyclosporine nephrotoxicity. The parameters to the diagnosis of acute rejection were sensitivity: 71.8%, specificity: 87.3%, positive predictive value: 50.9%, negative predictive value: 94.9% and accuracy 84.9%. The false positive results were mainly related to cytomegalovirus infection or to the administration of OKT3. In 10 out of 11 false negative results incipient immunoactivation was present alerting to the possibility of acute rejection. Kidney aspiration cytology is a useful tool for the sequential monitorization of acute rejection in renal transplant patients. The best results are reached when the results of aspiration cytology are analyzed with the clinical data.

Annual literature review of donor-specific HLA antibodies after organ transplantation.

PubMed

Kaneku, Hugo

2011-01-01

The literature review of post-transplant DSA published in 2011 shows: Observations after kidney and lung transplant in non-sensitized transplant recipients show that monitoring post-transplant HLA antibodies offers limited benefit in predicting acute rejection episodes. It remains to be seen if a different monitoring schedule and/ or studying other organs may show otherwise. Nevertheless, others have shown that monitoring post-transplant antibodies does identify patients at higher risk for chronic rejection. Studies in kidney, heart, and liver patients transplanted in the presence of preformed DSA show that detecting these antibodies early after transplant identifies a group of patients with greater risk for allograft dysfunction. New and larger studies using bortezomib and eculizumab to treat acute antibody-mediated rejection confirm earlier observations that these two therapies are effective in treating and preventing rejections. In general, identification of HLAantibodies and DSA after transplant is associated with higher rates of rejection and poor allograft survival in all organs examined. IgM antibodies appear to play an important role after lung transplants.

Mixed chimerism and split tolerance

PubMed Central

Al-Adra, David P.

2011-01-01

Establishing hematopoietic mixed chimerism can lead to donor-specific tolerance to transplanted organs and may eliminate the need for long-term immunosuppressive therapy, while also preventing chronic rejection. In this review, we discuss central and peripheral mechanisms of chimerism induced tolerance. However, even in the long-lasting presence of a donor organ or donor hematopoietic cells, some allogeneic tissues from the same donor can be rejected; a phenomenon known as split tolerance. With the current goal of creating mixed chimeras using clinically feasible amounts of donor bone marrow and with minimal conditioning, split tolerance may become more prevalent and its mechanisms need to be explored. Some predisposing factors that may increase the likelihood of split tolerance are immunogenicity of the graft, certain donor-recipient combinations, prior sensitization, location and type of graft and minimal conditioning chimerism induction protocols. Additionally, split tolerance may occur due to a differential susceptibility of various types of tissues to rejection. The mechanisms involved in a tissue’s differential susceptibility to rejection include the presence of polymorphic tissue-specific antigens and variable sensitivity to indirect pathway effector mechanisms. Finally, we review the clinical attempts at allograft tolerance through the induction of chimerism; studies that are revealing the complex relationship between chimerism and tolerance. This relationship often displays split tolerance, and further research into its mechanisms is warranted. PMID:22509425

Young Children’s Affective Responses to Acceptance and Rejection From Peers: A Computer-based Task Sensitive to Variation in Temperamental Shyness and Gender

PubMed Central

Howarth, Grace Z.; Guyer, Amanda E.; Pérez-Edgar, Koraly

2013-01-01

This study presents a novel task examining young children’s affective responses to evaluative feedback—specifically, social acceptance and rejection—from peers. We aimed to determine (1) whether young children report their affective responses to hypothetical peer evaluation predictably and consistently, and (2) whether young children’s responses to peer evaluation vary as a function of temperamental shyness and gender. Four- to seven-year-old children (N = 48) sorted pictures of unknown, similar-aged children into those with whom they wished or did not wish to play. Computerized peer evaluation later noted whether the pictured children were interested in a future playdate with participants. Participants then rated their affective responses to each acceptance or rejection event. Children were happy when accepted by children with whom they wanted to play, and disappointed when these children rejected them. Highly shy boys showed a wider range of responses to acceptance and rejection based on initial social interest, and may be particularly sensitive to both positive and negative evaluation. Overall, the playdate task captures individual differences in affective responses to evaluative peer feedback and is potentially amenable to future applications in research with young children, including pairings with psychophysiological measures. PMID:23997429

[Combined assay of soluble CD30 and hepatocyte growth factor for diagnosis of acute renal allograft rejection].

PubMed

Li, Chuan-jiang; Yu, Li-xin; Xu, Jian; Fu, Shao-jie; Deng, Wen-feng; Du, Chuan-fu; Wang, Yi-bin

2008-02-01

To study the value of detection of both preoperative soluble CD30 (sCD30) and hepatocyte growth factor (HGF) level 5 days after transplantation in the diagnosis of acute rejection of renal allograft. Preoperative serum sCD30 levels and HGF level 5 days after transplantation were determined in 65 renal-transplant recipients using enzyme-linked immunosorbent assay. The recipients were divided according to the sCD30 levels positivity. Receiver operating characteristic (ROC) curves were used to assess the value of HGF level on day 5 posttransplantation for diagnosis of acute renal allograft rejection, and the value of combined assay of the sCD30 and HGF levels was also estimated. After transplantation, 26 recipients developed graft rejection and 39 had uneventful recovery without rejection. With the cut-off value of sCD30 of 120 U/ml, the positivity rate of sCD30 was significantly higher in recipients with graft rejection than in those without (61.5% vs 17.9%, P<0.05). Recipients with acute rejection showed also significantly higher HGF levels on day 5 posttransplantation than those without rejection (P<0.05). ROC curve analysis indicated that HGF levels on day 5 posttransplantation was a good marker for diagnosis of acute renal allograft rejection, and at the cut-off value of 90 ug/L, the diagnostic sensitivity was 84.6% and specificity 76.9%. Evaluation of both the sCD30 and HGF levels significantly enhanced the diagnostic accuracy of acute graft rejection. Combined assay of serum sCD30 and HGF levels offers a useful means for diagnosis of acute renal allograft rejection.

Detection of urinary biomarkers for early diagnosis of acute renal allograft rejection by proteomic analysis.

PubMed

Jia, Xiongfei; Gan, Chengjun; Xiao, Ke; He, Weifeng; Zhang, Tao; Huang, Cibing; Wu, Xiongfei; Luo, Gaoxing; Wang, Xiaojuan; Hu, Jie; Tan, Jiangling; Zhang, Xiaorong; Larsen, Peter Mose; Wu, Jun

2009-06-01

Acute allograft rejection has been recognized as a major impediment to improved success in renal transplantation. Timely detection and control of rejection are very important for the improvement in long-term renal allograft survival. Thus, biomarkers for early diagnosis of acute rejection are required urgently to clinical medication. This study seeks to search for such biomarker candidates by comparing patients' pre-treatment urinary protein profiling with their post-treatment urinary protein profiling. A total of 15 significantly and consistently down-regulated protein candidates were identified. Among them, alpha-1-antichymotrypsin precursor (AACT), tumor rejection antigen gp96 (GP96) and Zn-Alpha-2-Glycoprotein (ZAG) were selected for further analysis. The results indicated that Western Blot assay of AACT, GP96 and ZAG had advanced the diagnosis time of acute renal rejection by 3 days, compared with current standard clinical observation and laboratory examination. Furthermore, the double-blind detection revealed that the accuracy, sensitivity and specificity of the diagnosis of acute renal rejection of AACT, GP96 and ZAG were 66.67%/100%/60%, 83.33%/100%/80% and 66.67%/100%/60%, respectively, and 100%/100%/100% in combination. In conclusion, urinary protein AACT, GP96 and ZAG could be a set of potential biomarkers for early non-invasive diagnosis of the acute rejection after renal transplantation. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Desensitization: Overcoming the Immunologic Barriers to Transplantation

PubMed Central

Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

2017-01-01

HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

Diagnostic Accuracy of the Aortic Dissection Detection Risk Score Plus D-Dimer for Acute Aortic Syndromes: The ADvISED Prospective Multicenter Study.

PubMed

Nazerian, Peiman; Mueller, Christian; Soeiro, Alexandre de Matos; Leidel, Bernd A; Salvadeo, Sibilla Anna Teresa; Giachino, Francesca; Vanni, Simone; Grimm, Karin; Oliveira, Múcio Tavares; Pivetta, Emanuele; Lupia, Enrico; Grifoni, Stefano; Morello, Fulvio

2018-01-16

Acute aortic syndromes (AASs) are rare and severe cardiovascular emergencies with unspecific symptoms. For AASs, both misdiagnosis and overtesting are key concerns, and standardized diagnostic strategies may help physicians to balance these risks. D-dimer (DD) is highly sensitive for AAS but is inadequate as a stand-alone test. Integration of pretest probability assessment with DD testing is feasible, but the safety and efficiency of such a diagnostic strategy are currently unknown. In a multicenter prospective observational study involving 6 hospitals in 4 countries from 2014 to 2016, consecutive outpatients were eligible if they had ≥1 of the following: chest/abdominal/back pain, syncope, perfusion deficit, and if AAS was in the differential diagnosis. The tool for pretest probability assessment was the aortic dissection detection risk score (ADD-RS, 0-3) per current guidelines. DD was considered negative (DD-) if <500 ng/mL. Final case adjudication was based on conclusive diagnostic imaging, autopsy, surgery, or 14-day follow-up. Outcomes were the failure rate and efficiency of a diagnostic strategy for ruling out AAS in patients with ADD-RS=0/DD- or ADD-RS ≤1/DD-. A total of 1850 patients were analyzed. Of these, 438 patients (24%) had ADD-RS=0, 1071 patients (58%) had ADD-RS=1, and 341 patients (18%) had ADD-RS >1. Two hundred forty-one patients (13%) had AAS: 125 had type A aortic dissection, 53 had type B aortic dissection, 35 had intramural aortic hematoma, 18 had aortic rupture, and 10 had penetrating aortic ulcer. A positive DD test result had an overall sensitivity of 96.7% (95% confidence interval [CI], 93.6-98.6) and a specificity of 64% (95% CI, 61.6-66.4) for the diagnosis of AAS; 8 patients with AAS had DD-. In 294 patients with ADD-RS=0/DD-, 1 case of AAS was observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1.9) and an efficiency of 15.9% (95% CI, 14.3-17.6) for the ADD-RS=0/DD- strategy. In 924 patients with ADD-RS ≤1/DD-, 3 cases of AAS were observed. This yielded a failure rate of 0.3% (95% CI, 0.1-1) and an efficiency of 49.9% (95% CI, 47.7-52.2) for the ADD-RS ≤1/DD- strategy. Integration of ADD-RS (either ADD-RS=0 or ADD-RS ≤1) with DD may be considered to standardize diagnostic rule out of AAS. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02086136. © 2017 American Heart Association, Inc.

Acute rejection in vascularized composite allotransplantation.

PubMed

Fischer, Sebastian; Lian, Christine G; Kueckelhaus, Maximilian; Strom, Terry B; Edelman, Elazer R; Clark, Rachel A; Murphy, George F; Chandraker, Anil K; Riella, Leonardo V; Tullius, Stefan G; Pomahac, Bohdan

2014-12-01

Acute rejection is the most common complication after vascularized composite allotransplantation (VCA). This review provides a state-of-the-art analysis of prevention, diagnosis and treatment of acute rejection episodes and highlights recent findings with the potential to improve patient care and enhance understanding of the underlying biologic processes. Recent reports suggest that maintenance immunosuppression dose reduction and steroid withdrawal are realistic goals in VCA, despite the known high immunogenicity of the skin component. It appears that utilization of sentinel flaps, in-depth histological analyses and application of novel biomarkers have facilitated early diagnosis and characterization of acute rejection episodes, leading to timely institution of appropriate therapy. The successful management of the first highly sensitized face transplant recipient suggests the possibility of carefully considering these high-risk VCA candidates for transplantation. Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression. Because of limitations in patient number and the duration of follow-up, the long-term safety and effectiveness of VCA remain unclear. Moreover, the tests currently used to diagnose acute rejection are of limited value. Better diagnostic tools and a better understanding of the immunologic events during acute rejection are therefore needed to improve diagnosis, treatment and outcomes of this life-changing restorative surgery.

[VALIDATION OF THE HUNGARIAN UNIFIED DYSKINESIA RATING SCALE].

PubMed

Horváth, Krisztina; Aschermann, Zsuzsanna; Ács, Péter; Bosnyák, Edit; Deli, Gabriella; Pál, Endre; Késmárki, Ildiko; Horvath, Réka; Takacs, Katalin; Balázs, Eva; Komoly, Sámuel; Bokor, Magdolna; Rigó, Eszter; Lajtos, Júlia; Takáts, Annamária; Tóth, Adrián; Klivényi, Péter; Dibó, György; Vecsei, László; Hidasi, Eszter; Nagy, Ferenc; Herceg, Mihály; Imre, Piroska; Kovács, Norbert

2015-05-30

The Unified Dyskinesia Rating Scale (UDysRS) was published in 2008. It was designed to be simultaneous valid, reliable and sensitive to therapeutic changes. The Movement Disorder Society organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new UDysRS and its validation process into Hungarian. After the translation of UDysRS into Hungarian and back-translated into English, it was reviewed by the UDysRS translation administration team. Subsequent cognitive pretesting was conducted with ten patients. For the large field testing phase, the Hungarian official working draft version of UDysRS was tested with 256 patients with Parkinson's disease having dyskinesia. Confirmatory factor analyses (CFA) determined whether the factor structure for the valid Spanish UDysRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the Spanish-language version. For the Hungarian UDysRS the CFI was 0.98. The overall factor structure of the Hungarian version was consistent with that of the Spanish version based on the high CFIs for the UDysRS in the CFA; therefore, this version was designated as the Official Hungarian Version Of The UDysRS.

Neuroaging through the Lens of the Resting State Networks

PubMed Central

2018-01-01

Resting state functional magnetic resonance imaging (rs-fMRI) allows studying spontaneous brain activity in absence of task, recording changes of Blood Oxygenation Level Dependent (BOLD) signal. rs-fMRI enables identification of brain networks also called Resting State Networks (RSNs) including the most studied Default Mode Network (DMN). The simplicity and speed of execution make rs-fMRI applicable in a variety of normal and pathological conditions. Since it does not require any task, rs-fMRI is particularly useful for protocols on patients, children, and elders, increasing participant's compliance and reducing intersubjective variability due to the task performance. rs-fMRI has shown high sensitivity in identification of RSNs modifications in several diseases also in absence of structural modifications. In this narrative review, we provide the state of the art of rs-fMRI studies about physiological and pathological aging processes. First, we introduce the background of resting state; then we review clinical findings provided by rs-fMRI in physiological aging, Mild Cognitive Impairment (MCI), Alzheimer Dementia (AD), and Late Life Depression (LLD). Finally, we suggest future directions in this field of research and its potential clinical applications. PMID:29568755

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri

In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 andmore » RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. In addition, these results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri

In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 andmore » RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. These results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.« less

The Drosophila foraging gene human orthologue PRKG1 predicts individual differences in the effects of early adversity on maternal sensitivity.

PubMed

Sokolowski, H Moriah; Vasquez, Oscar E; Unternaehrer, Eva; Sokolowski, Dustin J; Biergans, Stephanie D; Atkinson, Leslie; Gonzalez, Andrea; Silveira, Patricia P; Levitan, Robert; O'Donnell, Kieran J; Steiner, Meir; Kennedy, James; Meaney, Michael J; Fleming, Alison S; Sokolowski, Marla B

2017-04-01

There is variation in the extent to which childhood adverse experience affects adult individual differences in maternal behavior. Genetic variation in the animal foraging gene, which encodes a cGMP-dependent protein kinase, contributes to variation in the responses of adult fruit flies, Drosophila melanogaster , to early life adversity and is also known to play a role in maternal behavior in social insects. Here we investigate genetic variation in the human foraging gene ( PRKG1 ) as a predictor of individual differences in the effects of early adversity on maternal behavior in two cohorts. We show that the PRKG1 genetic polymorphism rs2043556 associates with maternal sensitivity towards their infants. We also show that rs2043556 moderates the association between self-reported childhood adversity of the mother and her later maternal sensitivity. Mothers with the TT allele of rs2043556 appeared buffered from the effects of early adversity, whereas mothers with the presence of a C allele were not. Our study used the Toronto Longitudinal Cohort (N=288 mother-16 month old infant pairs) and the Maternal Adversity and Vulnerability and Neurodevelopment Cohort (N=281 mother-18 month old infant pairs). Our findings expand the literature on the contributions of both genetics and gene-environment interactions to maternal sensitivity, a salient feature of the early environment relevant for child neurodevelopment.

Leptin Receptor Gene Variant rs11804091 Is Associated with BMI and Insulin Resistance in Spanish Female Obese Children: A Case-Control Study

PubMed Central

Rupérez, Azahara I.; Gil-Campos, Mercedes; Leis, Rosaura; Cañete, Ramón; Tojo, Rafael

2017-01-01

Leptin is an endocrine hormone that has a critical role in body weight homoeostasis and mediates its effects via the leptin receptor (LEPR). Common polymorphisms in the genes coding leptin receptors have been associated with metabolic abnormalities. We assessed the association of 28 LEPR polymorphisms with body mass index (BMI) and their relationship with obesity-related phenotypes, inflammation and cardiovascular disease risk biomarkers. A multicentre case-control study was conducted in 522 children (286 with obesity and 236 with normal-BMI). All anthropometric, metabolic factors and biomarkers were higher in children with obesity except apolipoprotein (Apo)-AI, cholesterol, high-density lipoprotein cholesterol (HDL-c), and adiponectin, which were lower in the obesity group; and glucose, low-density lipoprotein cholesterol (LDL-c), and matrix metalloproteinase-9 that did not differ between groups. We identified the associations between rs11208659, rs11804091, rs10157275, rs9436303 and rs1627238, and BMI in the whole population, as well as the association of rs11804091, rs10157275, and rs1327118 with BMI in the female group, although only the rs11804091 remained associated after Bonferroni correction (p = 0.038). This single nucleotide polymorphisms (SNP) was also associated with insulin (p = 0.004), homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.006), quantitative insulin sensitivity check index (QUICKI) (p = 0.005) and adiponectin (p = 0.046) after adjusting for age, Tanner stage and BMI. Our results show a sex-specific association between the rs11804091 and obesity suggesting an influence of this SNP on insulin resistance. PMID:28771179

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uhm, Z. Lucas; Zhang Bing; Hascoeet, Romain

We perform a detailed study on the dynamics of a relativistic blast wave with the presence of a long-lived reverse shock (RS). Although a short-lived RS has been widely considered, the RS is believed to be long-lived as a consequence of a stratification expected on the ejecta Lorentz factors. The existence of a long-lived RS causes the forward shock (FS) dynamics to deviate from a self-similar Blandford-McKee solution. Employing the ''mechanical model'' that correctly incorporates the energy conservation, we present an accurate solution for both the FS and RS dynamics. We conduct a sophisticated calculation of the afterglow emission. Adoptingmore » a Lagrangian description of the blast wave, we keep track of an adiabatic evolution of numerous shells between the FS and RS. An evolution of the electron spectrum is also followed individually for every shell. We then find the FS and RS light curves by integrating over the entire FS and RS shocked regions, respectively. Exploring a total of 20 different ejecta stratifications, we explain in detail how a stratified ejecta affects its blast wave dynamics and afterglow light curves. We show that, while the FS light curves are not sensitive to the ejecta stratifications, the RS light curves exhibit much richer features, including steep declines, plateaus, bumps, re-brightenings, and a variety of temporal decay indices. These distinctive RS features may be observable if the RS has higher values of the microphysics parameters than the FS. We discuss possible applications of our results in understanding the gamma-ray burst afterglow data.« less

Panic disorder respiratory subtype: psychopathology, laboratory challenge tests, and response to treatment.

PubMed

Freire, Rafael C; Perna, Giampaolo; Nardi, Antonio E

2010-01-01

Our objective is to summarize the new findings concerning the respiratory subtype (RS) of panic disorder (PD) since its first description. Two searches were made in the Institute for Scientific Information Web of Science: with the keywords "panic disorder" and "respiratory symptoms," and all articles that cited Briggs and colleagues' 1993 article "Subtyping of Panic Disorder by Symptom Profile" (Br J Psychiatry 1993;163:201-9). Altogether, 133 articles were reviewed. We describe and discuss RS epidemiology, genetics, psychopathology, demographic features, clinical features, correlations with the respiratory system, traumatic suffocation history, provocative tests, and nocturnal panic. Compared to patients with the nonrespiratory subtype (non-RS), the RS patients had higher familial history of PD, lower comorbidity with depression, longer duration of illness, lower neuroticism scores, and higher scores in severity scales, such as the Panic and Agoraphobia Scale, Panic-Agoraphobia Spectrum scale and the Clinical Global Impression scale. Tests to induce panic attacks, such as those with CO(2), hyperventilation, and caffeine, produce panic attacks in a higher proportion of RS patients than non-RS patients. Differences in the subtypes' improvement with the pharmacologic treatment were found. There are also some controversial findings regarding the RS, including the age of onset of PD, and alcohol and tobacco use in RS patients. Some characteristics, such as the increased sensitivity to CO(2) and the higher familial history of PD, clearly distinguish the RS from the non-RS. Nevertheless, there are also controversial findings. More studies are needed to determine the validity of the RS subtype.

Planned versus actual outcomes as a result of animal feeding operation decisions for managing phosphorus.

PubMed

Cabot, Perry E; Nowak, Pete

2005-01-01

The paper explores how decisions made on animal feeding operations (AFOs) influence the management of manure and phosphorus. Variability among these decisions from operation to operation and from field to field can influence the validity of nutrient loss risk assessments. These assessments are based on assumptions that the decision outcomes regarding manure distribution will occur as they are planned. The discrepancy between planned versus actual outcomes in phosphorus management was explored on nine AFOs managing a contiguous set of 210 fields in south-central Wisconsin. A total of 2611 soil samples were collected and multiple interviews conducted to assign phosphorus index (PI) ratings to the fields. Spearman's rank correlation coefficients (r(S)) indicated that PI ratings were less sensitive to soil test phosphorus (STP) levels (r(S) = 0.378), universal soil loss equation (USLE) (r(S) = 0.261), ratings for chemical fertilizer application (r(S) = 0.185), and runoff class (r(S) = -0.089), and more sensitive to ratings for manure application (r(S) = 0.854). One-way ANOVA indicated that mean field STP levels were more homogenous than field PI ratings between AFOs. Kolmogorov-Smirnov (K-S) tests displayed several nonsignificant comparisons for cumulative distribution functions, S(x), of mean STP levels on AFO fields. On the other hand, the K-S tests of S(x) for PI ratings indicated that the majority of these S(x) functions were significantly different between AFOs at or greater than the 0.05 significance level. Interviews suggested multiple reasons for divergence between planned and actual outcomes in managing phosphorus, and that this divergence arises at the strategic, tactical, and operational levels of decision-making.

Association between allelic variants of the human glucocorticoid receptor gene and autoimmune diseases: A systematic review and meta-analysis.

PubMed

Herrera, Cristian; Marcos, Miguel; Carbonell, Cristina; Mirón-Canelo, José Antonio; Espinosa, Gerard; Cervera, Ricard; Chamorro, Antonio-Javier

2018-05-01

The human glucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved. A meta-analysis was conducted with a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. In addition, sub-analysis by ethnicity, sensitivity analysis and tests for heterogeneity of the results were performed. Eleven studies met the inclusion criteria for meta-analysis. We found no evidence that the analysed NR3C1 polymorphisms, rs6198, rs56149945, and rs6189/rs6190, modulate the risk of developing a systemic autoimmune disease. Nonetheless, a protective role for the minor allele of rs41423247 was found among Caucasians (OR=0.78; 95% CI: 0.65, 0.92; P=0.004). A subgroup analysis according to underlying diseases revealed no significant association either for Behçet's disease or rheumatoid arthritis, while correlations between NR3C1 polymorphisms and disease activity or response to glucocorticoids could not be evaluated due to insufficient data. There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians. Copyright © 2018 Elsevier B.V. All rights reserved.

Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.

PubMed

Hayashi, Teruo; Su, Tsung-Ping

2007-11-02

Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca(2+) directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca(2+)-sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca(2+) depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca(2+) signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival.

Interaction of CD38 Variant and Chronic Interpersonal Stress Prospectively Predicts Social Anxiety and Depression Symptoms Over Six Years

PubMed Central

Tabak, Benjamin A.; Vrshek-Schallhorn, Suzanne; Zinbarg, Richard E.; Prenoveau, Jason M.; Mineka, Susan; Redei, Eva E.; Adam, Emma K.; Craske, Michelle G.

2015-01-01

Variation in the CD38 gene, which regulates secretion of the neuropeptide oxytocin, has been associated with several social phenotypes. Specifically, rs3796863 A allele carriers have demonstrated increased social sensitivity. In 400 older adolescents, we used trait-state-occasion modeling to investigate how rs3796863 genotype, baseline ratings of chronic interpersonal stress, and their gene-environment (GxE) interaction predicted trait social anxiety and depression symptoms over six years. We found significant GxE effects for CD38 A-carrier genotypes and chronic interpersonal stress at baseline predicting greater social anxiety and depression symptoms. A significant GxE effect of smaller magnitude was also found for C/C genotype and chronic interpersonal stress predicting greater depression; however, this effect was small compared to the main effect of chronic interpersonal stress. Thus, in the context of chronic interpersonal stress, heightened social sensitivity associated with the rs3796863 A allele may prospectively predict risk for social anxiety and (to a lesser extent) depression. PMID:26958455

α5GABAA Receptors Mediate Tonic Inhibition in the Spinal Cord Dorsal Horn and Contribute to the Resolution Of Hyperalgesia.

PubMed

Perez-Sanchez, Jimena; Lorenzo, Louis-Etienne; Lecker, Irene; Zurek, Agnieszka A; Labrakakis, Charalampos; Bridgwater, Erica M; Orser, Beverley A; De Koninck, Yves; Bonin, Robert P

2017-06-01

Neuronal inhibition mediated by GABA A receptors constrains nociceptive processing in the spinal cord, and loss of GABAergic inhibition can produce allodynia and hyperalgesia. Extrasynaptic α5 subunit-containing GABA A receptors (α5GABA A Rs) generate a tonic conductance that inhibits neuronal activity and constrains learning and memory; however, it is unclear whether α5GABA A Rs similarly generate a tonic conductance in the spinal cord dorsal horn to constrain nociception. We assessed the distribution of α5GABA A Rs in the spinal cord dorsal horn by immunohistochemical analysis, and the activity and function of α5GABA A Rs in neurons of the superficial dorsal horn using electrophysiological and behavioral approaches in male, null-mutant mice lacking the GABA A R α5 subunit (Gabra5-/-) and wild-type mice (WT). The expression of α5GABA A Rs in the superficial dorsal horn followed a laminar pattern of distribution, with a higher expression in lamina II than lamina I. Similarly, the tonic GABA A current in lamina II neurons had a larger contribution from α5GABA A Rs than in lamina I, with no significant contribution of these receptors to synaptic GABA A current. In behavioural tests, WT and Gabra5-/- mice exhibited similar acute thermal and mechanical nociception, and similar mechanical sensitization immediately following intraplantar capsaicin or Complete Freund's Adjuvant (CFA). However, Gabra5-/- mice showed prolonged recovery from sensitization in these models, and increased responses in the late phase of the formalin test. Overall, our data suggest that tonically-active α5GABA A Rs in the spinal cord dorsal horn accelerate the resolution of hyperalgesia and may therefore serve as a novel therapeutic target to promote recovery from pathological pain. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The common occurrence of epistasis in the determination of human pigmentation and its impact on DNA-based pigmentation phenotype prediction.

PubMed

Pośpiech, Ewelina; Wojas-Pelc, Anna; Walsh, Susan; Liu, Fan; Maeda, Hitoshi; Ishikawa, Takaki; Skowron, Małgorzata; Kayser, Manfred; Branicki, Wojciech

2014-07-01

The role of epistatic effects in the determination of complex traits is often underlined but its significance in the prediction of pigmentation phenotypes has not been evaluated so far. The prediction of pigmentation from genetic data can be useful in forensic science to describe the physical appearance of an unknown offender, victim, or missing person who cannot be identified via conventional DNA profiling. Available forensic DNA prediction systems enable the reliable prediction of several eye and hair colour categories. However, there is still space for improvement. Here we verified the association of 38 candidate DNA polymorphisms from 13 genes and explored the extent to which interactions between them may be involved in human pigmentation and their impact on forensic DNA prediction in particular. The model-building set included 718 Polish samples and the model-verification set included 307 independent Polish samples and additional 72 samples from Japan. In total, 29 significant SNP-SNP interactions were found with 5 of them showing an effect on phenotype prediction. For predicting green eye colour, interactions between HERC2 rs12913832 and OCA2 rs1800407 as well as TYRP1 rs1408799 raised the prediction accuracy expressed by AUC from 0.667 to 0.697 and increased the prediction sensitivity by >3%. Interaction between MC1R 'R' variants and VDR rs731236 increased the sensitivity for light skin by >1% and by almost 3% for dark skin colour prediction. Interactions between VDR rs1544410 and TYR rs1042602 as well as between MC1R 'R' variants and HERC2 rs12913832 provided an increase in red/non-red hair prediction accuracy from an AUC of 0.902-0.930. Our results thus underline epistasis as a common phenomenon in human pigmentation genetics and demonstrate that considering SNP-SNP interactions in forensic DNA phenotyping has little impact on eye, hair and skin colour prediction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Validating Early Post–Transplant Outcomes Reported for Recipients of Deceased Donor Kidney Transplants

PubMed Central

Potluri, Vishnu S.; Hall, Isaac E.; Ficek, Joseph; Doshi, Mona D.; Butrymowicz, Isabel; Weng, Francis L.; Schröppel, Bernd; Thiessen-Philbrook, Heather; Reese, Peter P.

2016-01-01

Background and objectives Data reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post–transplant outcome measures is unknown. Design, setting, participants, & measurements The Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post-transplant outcomes of delayed graft function (DGF; defined as dialysis in the first post–transplant week), acute rejection, and post–transplant serum creatinine reported to the OPTN with data collected for the DDS. Results Median kidney donor risk index was 1.22 (interquartile range [IQR], 0.97–1.53). Median recipient age was 55 (IQR, 46–63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%–100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92). Conclusions OPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft function at 6 months as a useful outcome. PMID:26668026

Integrative Approach to Pain Genetics Identifies Pain Sensitivity Loci across Diseases

PubMed Central

Ruau, David; Dudley, Joel T.; Chen, Rong; Phillips, Nicholas G.; Swan, Gary E.; Lazzeroni, Laura C.; Clark, J. David

2012-01-01

Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI), derived from Medical Subject Heading (MESH) annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10−10) for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10−4, 1.8×10−4, and 2.2×10−4 respectively). Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates. PMID:22685391

Activated effector and memory T cells contribute to circulating sCD30: potential marker for islet allograft rejection.

PubMed

Saini, D; Ramachandran, S; Nataraju, A; Benshoff, N; Liu, W; Desai, N; Chapman, W; Mohanakumar, T

2008-09-01

T-cell activation up-regulates CD30 resulting in an increase in serum soluble CD30 (sCD30). CD4+ T cells, a major source for sCD30, play a significant role in the pathogenesis of rejection. In this study, sCD30 was measured pre- and posttransplant in mouse islet allograft models and human islet allograft recipients. sCD30 was measured by ELISA in diabetic C57BL/6, CD4Knockout (KO) and CD8KO islet allograft recipients. sCD30 increased significantly prior to rejection (1.8 +/- 1 days) in 80% of allograft recipients. Sensitization with donor splenocytes, or a second graft, further increased sCD30 (282.5 +/- 53.5 for the rejecting first graft vs. 374.6 +/- 129 for the rejecting second graft) prior to rejection suggesting memory CD4+ T cells contribute to sCD30. CD4KO failed to reject islet allograft and did not demonstrate sCD30 increase. CD8KO showed elevated (227 +/- 107) sCD30 (1 day) prior to rejection. High pretransplant sCD30 (>20 U/ml) correlated with poor outcome in human islet allograft recipients. Further, increase in sCD30 posttransplant preceded (3-4 months) loss of islet function. We conclude that sCD30 is released from activated CD4 T cells prior to islet allograft rejection and monitoring sCD30 can be a valuable adjunct in the follow-up of islet transplant recipients.

Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans.

PubMed

Sevastianova, Ksenia; Kotronen, Anna; Gastaldelli, Amalia; Perttilä, Julia; Hakkarainen, Antti; Lundbom, Jesper; Suojanen, Laura; Orho-Melander, Marju; Lundbom, Nina; Ferrannini, Eleuterio; Rissanen, Aila; Olkkonen, Vesa M; Yki-Järvinen, Hannele

2011-07-01

The rs738409 C→G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance. The I148M mutation impedes triglyceride hydrolysis in vitro, and its carriers have an increased risk of developing severe liver disease. We explored whether the rs738409 PNPLA3 G allele influences the ability of weight loss to decrease liver fat or change insulin sensitivity. We recruited 8 subjects who were homozygous for the rs738409 PNPLA3 G allele (PNPLA3-148MM) and 10 who were homozygous for the rs738409 PNPLA3 C allele (PNPLA3-148II). To allow comparison of changes in liver fat, the groups were matched with respect to baseline age, sex, body mass index, and liver fat. The subjects were placed on a hypocaloric low-carbohydrate diet for 6 d. Liver fat content (proton magnetic resonance spectroscopy), whole-body insulin sensitivity of glucose metabolism (euglycemic clamp technique), and lipolysis ([(2)H(5)]glycerol infusion) were measured before and after the diet. At baseline, fasting serum insulin and C-peptide concentrations were significantly lower in the PNPLA3-148MM group than in the PNPLA3-148II group, as predicted by study design. Weight loss was not significantly different between groups (PNPLA3-148MM: -3.1 ± 0.5 kg; PNPLA3-148II: -3.1 ± 0.4 kg). Liver fat decreased by 45% in the PNPLA3-148MM group (P < 0.001) and by 18% in the PNPLA3-148II group (P < 0.01). Weight loss is effective in decreasing liver fat in subjects who are homozygous for the rs738409 PNPLA3 G or C allele. This trial was registered at www.hus.fi as 233775.

Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: replication and extension of a gene-environment interaction.

PubMed

van Winkel, Mark; Peeters, Frenk; van Winkel, Ruud; Kenis, Gunter; Collip, Dina; Geschwind, Nicole; Jacobs, Nele; Derom, Catherine; Thiery, Evert; van Os, Jim; Myin-Germeys, Inez; Wichers, Marieke

2014-06-01

A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factor(Val66Met) (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals. Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in "Val/Met" carriers of BDNF(Val66Met) compared to "Val/Val" carriers. Positive emotions neutralized the moderating effect of BDNF(Val66Met) genotype on social stress sensitivity in a dose-response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample. In conclusion, ESM has important advantages in gene-environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Comparison of the performance of rapid prescreening, 10% random review, and clinical risk criteria as methods of internal quality control in cervical cytopathology.

PubMed

Tavares, Suelene B N; Alves de Sousa, Nadja L; Manrique, Edna J C; Pinheiro de Albuquerque, Zair B; Zeferino, Luiz C; Amaral, Rita G

2008-06-25

Rapid prescreening (RPS) is an internal quality-control (IQC) method that is used both to reduce errors in the laboratory and to measure the sensitivity of routine screening (RS). Little direct comparison data are available comparing RPS with other more widely used IQC methods. The authors compared the performance of RPS, 10% random review of negative smears (R-10%), and directed rescreening of negative smears based on clinical risk criteria (RCRC) over 1 year in a community clinic setting. In total, 6,135 smears were evaluated. The sensitivity of RS alone was 71.3%. RPS detected significantly more (132 cases) false-negative (FN) cases than either R-10% (7 cases) or RCRC (32 cases). RPS significantly improved the overall sensitivity of the laboratory (71.3-92.2%; P = .001); neither R-10% nor RCRC significantly changed the sensitivity of RS. RPS was not as specific as the other methods, although nearly 68% of all abnormalities detected by RPS were verified as real. RPS of 100% of smears required the same amount of time as RCRC but required twice as much time as R-10%. The current results demonstrated that RPS is a much more effective IQC method than either R-10% or RCRC. RPS detects significantly more errors and can improve the overall sensitivity of a laboratory with either a modest increase or no increase in overall time spent on IQC. R-10% is an insensitive IQC method, and neither R-10% nor RCRC can significantly improve the overall sensitivity of a laboratory. (c) 2008 American Cancer Society.

Development of a liquid xenon time projection chamber for the XENON dark matter search

NASA Astrophysics Data System (ADS)

Ni, Kaixuan

This thesis describes the research conducted for the XENON dark matter direct detection experiment. The tiny energy and small cross-section, from the interaction of dark matter particle on the target, requires a low threshold and sufficient background rejection capability of the detector. The XENON experiment uses dual phase technology to detect scintillation and ionization simultaneously from an event in liquid xenon (LXe). The distinct ratio, between scintillation and ionization, for nuclear recoil and electron recoil events provides excellent background rejection potential. The XENON detector is designed to have 3D position sensitivity down to mm scale, which provides additional event information for background rejection. Started in 2002, the XENON project made steady progress in the R&D phase during the past few years. Those include developing sensitive photon detectors in LXe, improving the energy resolution and LXe purity for detecting very low energy events. Two major quantities related to the dark matter detection, the scintillation efficiency and ionization yield of nuclear recoils in LXe, have been established. A prototype dual phase detector (XENON3) has been built and tested extensively in above ground laboratory. The 3D position sensitivity, as well as the background discrimination potential demonstrated from the XENON3 prototype, allows the construction of a 10 kg scale detector (XENON10), to be deployed underground in early 2006. With 99.5% electron recoil rejection efficiency and 16 keVr nuclear recoil energy threshold, XENON10 will be able to probe the WIMP-nucleon cross-section down to 2 x 10-44 cm2 in the supersymmetry parameter space, after one month operation in the Gran Sasso underground laboratory.

Parametric design and analysis on the landing gear of a planet lander using the response surface method

NASA Astrophysics Data System (ADS)

Zheng, Guang; Nie, Hong; Luo, Min; Chen, Jinbao; Man, Jianfeng; Chen, Chuanzhi; Lee, Heow Pueh

2018-07-01

The purpose of this paper is to obtain the design parameter-landing response relation for designing the configuration of the landing gear in a planet lander quickly. To achieve this, parametric studies on the landing gear are carried out using the response surface method (RSM), based on a single landing gear landing model validated by experimental results. According to the design of experiment (DOE) results of the landing model, the RS (response surface)-functions of the three crucial landing responses are obtained, and the sensitivity analysis (SA) of the corresponding parameters is performed. Also, two multi-objective optimizations designs on the landing gear are carried out. The analysis results show that the RS (response surface)-model performs well for the landing response design process, with a minimum fitting accuracy of 98.99%. The most sensitive parameters for the three landing response are the design size of the buffers, struts friction and the diameter of the bending beam. Moreover, the good agreement between the simulated model and RS-model results are obtained in two optimized designs, which show that the RS-model coupled with the FE (finite element)-method is an efficient method to obtain the design configuration of the landing gear.

Use of Humanized RS-ATL8 Reporter System for Detection of Allergen-Specific IgE Sensitization in Human Food Allergy.

PubMed

Ali, Eman Ali; Nakamura, Ryosuke; Falcone, Franco H

2017-01-01

Allergen-specific Immunoglobulin E (IgE) determination lies at the heart of diagnosis of sensitization to food and other allergens. In the past few years, reporter systems capable of detecting the presence of allergen-specific IgE have been developed by several labs. These rely on humanized rat basophil leukemia cell lines stably transfected with reporter genes such as firefly luciferase. In this chapter, we describe protocols for the use of the RS-ATL8 cell line (IgE cross-linking-induced luciferase expression; EXiLE) in 96-well and 384-well formats. We also describe optional treatment steps for enveloped virus and complement inactivation.

Assessment of Immune Isolation of Allogeneic Mouse Pancreatic Progenitor Cells by a Macroencapsulation Device

PubMed Central

Faleo, Gaetano; Lee, Karim; Nguyen, Vinh; Tang, Qizhi

2016-01-01

Background Embryonic-stem-cell (ESC)-derived islets hold the promise of providing a renewable source of tissue for the treatment of insulin-dependent diabetes. Encapsulation may allow ESC-derived islets to be transplanted without immunosuppression, thus enabling wider application of this therapy. Methods In this study, we investigated the immunogenicity of mouse pancreatic progenitor cells and efficacy of a new macroencapsulation device in protecting these cells against alloimmune and autoimmune responses in mouse models. Results Mouse pancreatic progenitor cells activated the indirect but not the direct pathway of alloimmune response and were promptly rejected in immune competent hosts. The new macroencapsulation device abolished T cell activation induced by allogeneic splenocytes and protected allogeneic MIN6 β cells and pancreatic progenitors from rejection even in pre-sensitized recipients. In addition, the device was effective in protecting MIN6 cells in spontaneously diabetic non-obese diabetic recipients against both alloimmune and recurring autoimmune responses. Conclusion Our results demonstrate that macroencapsulation can effectively prevent immune sensing and rejection of allogeneic pancreatic progenitor cells in fully sensitized and autoimmune hosts. PMID:26982952

Common Genetic Variation in the Human FNDC5 Locus, Encoding the Novel Muscle-Derived ‘Browning’ Factor Irisin, Determines Insulin Sensitivity

PubMed Central

Staiger, Harald; Böhm, Anja; Scheler, Mika; Berti, Lucia; Machann, Jürgen; Schick, Fritz; Machicao, Fausto; Fritsche, Andreas; Stefan, Norbert; Weigert, Cora; Krook, Anna; Häring, Hans-Ulrich; de Angelis, Martin Hrabě

2013-01-01

Aims/hypothesis Recently, the novel myokine irisin was described to drive adipose tissue ‘browning’, to increase energy expenditure, and to improve obesity and insulin resistance in high fat-fed mice. Here, we assessed whether common single nucleotide polymorphisms (SNPs) in the FNDC5 locus, encoding the irisin precursor, contribute to human prediabetic phenotypes (overweight, glucose intolerance, insulin resistance, impaired insulin release). Methods A population of 1,976 individuals was characterized by oral glucose tolerance tests and genotyped for FNDC5 tagging SNPs. Subgroups underwent hyperinsulinaemic-euglycaemic clamps, magnetic resonance imaging/spectroscopy, and intravenous glucose tolerance tests. From 37 young and 14 elderly participants recruited in two different centres, muscle biopsies were obtained for the preparation of human myotube cultures. Results After appropriate adjustment and Bonferroni correction for the number of tested variants, SNPs rs16835198 and rs726344 were associated with in vivo measures of insulin sensitivity. Via interrogation of publicly available data from the Meta-Analyses of Glucose and Insulin-related traits Consortium, rs726344’s effect on insulin sensitivity was replicated. Moreover, novel data from human myotubes revealed a negative association between FNDC5 expression and appropriately adjusted in vivo measures of insulin sensitivity in young donors. This finding was replicated in myotubes from elderly men. Conclusions/interpretation This study provides evidence that the FNDC5 gene, encoding the novel myokine irisin, determines insulin sensitivity in humans. Our gene expression data point to an unexpected insulin-desensitizing effect of irisin. PMID:23637927

Genetic variants in AKR1B10 associate with human eating behavior.

PubMed

Rohde, Kerstin; Federbusch, Martin; Horstmann, Annette; Keller, Maria; Villringer, Arno; Stumvoll, Michael; Tönjes, Anke; Kovacs, Peter; Böttcher, Yvonne

2015-03-25

The human Aldoketoreductase 1B10 gene (AKR1B10) encodes one of the enzymes belonging to the family of aldoketoreductases and may be involved in detoxification of nutrients during digestion. Further, AKR1B10 mRNA (messenger ribonucleic acid) expression was diminished in brain regions potentially involved in the regulation of eating behavior in rats which are more sensitive to cocaine and alcohol. We hypothesized that the human AKR1B10 gene may also play a role in the regulation of human eating behavior. We investigated the effects of 5 genetic variants of AKR1B10 on human eating behavior among 548 subjects from a German self-contained population, the Sorbs, and in 350 subjects from another independent German cohort. Among the Sorbs, we observed nominal associations with disinhibition at the 5' untranslated region (5' UTR) variant rs10232478 and the intragenic variants rs1834150 and rs782881 (all P ≤ 0.05). Further, we detected a relationship of rs1834150 and rs782881 with waist, smoking consumption (rs782881) and coffee consumption (rs1834150) (all P ≤ 0.05). Albeit non-significant, replication analyses revealed similar effect directions for disinhibition at rs1834150 (combined P = 0.0096). Moreover, in the replication cohort we found rs1834150 related to increased restraint scores with a similar direction as in the Sorbs (combined P = 0.0072). Our data suggest that genetic variants in the AKR1B10 locus may influence human eating behavior.

Hubs of Anticorrelation in High-Resolution Resting-State Functional Connectivity Network Architecture.

PubMed

Gopinath, Kaundinya; Krishnamurthy, Venkatagiri; Cabanban, Romeo; Crosson, Bruce A

2015-06-01

A major focus of brain research recently has been to map the resting-state functional connectivity (rsFC) network architecture of the normal brain and pathology through functional magnetic resonance imaging. However, the phenomenon of anticorrelations in resting-state signals between different brain regions has not been adequately examined. The preponderance of studies on resting-state fMRI (rsFMRI) have either ignored anticorrelations in rsFC networks or adopted methods in data analysis, which have rendered anticorrelations in rsFC networks uninterpretable. The few studies that have examined anticorrelations in rsFC networks using conventional methods have found anticorrelations to be weak in strength and not very reproducible across subjects. Anticorrelations in rsFC network architecture could reflect mechanisms that subserve a number of important brain processes. In this preliminary study, we examined the properties of anticorrelated rsFC networks by systematically focusing on negative cross-correlation coefficients (CCs) among rsFMRI voxel time series across the brain with graph theory-based network analysis. A number of methods were implemented to enhance the neuronal specificity of resting-state functional connections that yield negative CCs, although at the cost of decreased sensitivity. Hubs of anticorrelation were seen in a number of cortical and subcortical brain regions. Examination of the anticorrelation maps of these hubs indicated that negative CCs in rsFC network architecture highlight a number of regulatory interactions between brain networks and regions, including reciprocal modulations, suppression, inhibition, and neurofeedback.

Association of interactions between dietary salt consumption and hypertension-susceptibility genetic polymorphisms with blood pressure among Japanese male workers.

PubMed

Imaizumi, Takahiro; Ando, Masahiko; Nakatochi, Masahiro; Maruyama, Shoichi; Yasuda, Yoshinari; Honda, Hiroyuki; Kuwatsuka, Yachiyo; Kato, Sawako; Kondo, Takaaki; Iwata, Masamitsu; Nakashima, Toru; Yasui, Hiroshi; Takamatsu, Hideki; Okajima, Hiroshi; Yoshida, Yasuko; Matsuo, Seiichi

2017-06-01

Blood pressure is influenced by hereditary factors and dietary habits. The objective of this study was to examine the effect of dietary salt consumption and single-nucleotide polymorphisms (SNPs) on blood pressure (BP). This was a cross-sectional analysis of 2728 male participants who participated in a health examination in 2009. Average dietary salt consumption was estimated using electronically collected meal purchase data from cafeteria. A multivariate analysis, adjusting for clinically relevant factors, was conducted to examine whether the effect on BP of salt consumption, SNPs, and interaction between salt consumption and each SNP. This study examined the SNPs AGT rs699 (Met235Thr), ADD1 rs4961 (Gly460Trp), NPPA rs5063 (Val32Met), GPX1 rs1050450 (Pro198Leu), and AGTR1 rs5186 (A1166C) in relation to hypertension and salt sensitivity. BP was not significantly associated with SNPs or salt consumption. The interaction between salt consumption and SNPs with systolic BP showed a significant association in NPPA rs5063 (Val32Met) (P = 0.023) and a marginal trend toward significance in rs4961 and rs1050450 (P = 0.060 and 0.067, respectively). The effect of salt consumption on BP differed by genotype. Dietary salt consumption and genetic variation can predict a high risk of hypertension.

The Vibrio parahaemolyticus ToxRS Regulator Is Required for Stress Tolerance and Colonization in a Novel Orogastric Streptomycin-Induced Adult Murine Model

PubMed Central

Whitaker, W. Brian; Parent, Michelle A.; Boyd, Aoife; Richards, Gary P.

2012-01-01

Vibrio parahaemolyticus, a marine bacterium, is the causative agent of gastroenteritis associated with the consumption of seafood. It contains a homologue of the toxRS operon that in V. cholerae is the key regulator of virulence gene expression. We examined a nonpolar mutation in toxRS to determine the role of these genes in V. parahaemolyticus RIMD2210633, an O3:K6 isolate, and showed that compared to the wild type, ΔtoxRS was significantly more sensitive to acid, bile salts, and sodium dodecyl sulfate stresses. We demonstrated that ToxRS is a positive regulator of ompU expression, and that the complementation of ΔtoxRS with ompU restores stress tolerance. Furthermore, we showed that ToxRS also regulates type III secretion system genes in chromosome I via the regulation of the leuO homologue VP0350. We examined the effect of ΔtoxRS in vivo using a new orogastric adult murine model of colonization. We demonstrated that streptomycin-treated adult C57BL/6 mice experienced prolonged intestinal colonization along the entire intestinal tract by the streptomycin-resistant V. parahaemolyticus. In contrast, no colonization occurred in non-streptomycin-treated mice. A competition assay between the ΔtoxRS and wild-type V. parahaemolyticus strains marked with the β-galactosidase gene lacZ demonstrated that the ΔtoxRS strain was defective in colonization compared to the wild-type strain. This defect was rescued by ectopically expressing ompU. Thus, the defect in stress tolerance and colonization in ΔtoxRS is solely due to OmpU. To our knowledge, the orogastric adult murine model reported here is the first showing sustained intestinal colonization by V. parahaemolyticus. PMID:22392925

Muscarinic Receptors Modulate Dendrodendritic Inhibitory Synapses to Sculpt Glomerular Output

PubMed Central

Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus

2015-01-01

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. PMID:25855181

Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.

PubMed

Liu, Shaolin; Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus; Shipley, Michael T

2015-04-08

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. Copyright © 2015 the authors 0270-6474/15/355680-13$15.00/0.

Pharmacogenetics of clozapine response and induced weight gain: A comprehensive review and meta-analysis.

PubMed

Gressier, Florence; Porcelli, Stefano; Calati, Raffaella; Serretti, Alessandro

2016-02-01

Clozapine (CLZ) is the prototype atypical antipsychotic and it has many advantages over other antipsychotic drugs. Several data suggest that both CLZ response and induced weight gain are strongly determined by genetic variability. However, results remain mainly inconclusive. We aim to review the literature data about pharmacogenetics studies on CLZ efficacy, focusing on pharmacodynamic genes. Further, we performed meta-analyses on response when at least three studies for each polymorphism were available. Sensitivity analyses were conducted on Caucasian population when feasible. Electronic literature search was performed to identify pertinent studies published until May 2014 using PubMed, ISI Web of Knowledge and PsycINFO databases. For meta-analyses, data were entered and analyzed through RevMan version 5.2 using a random-effect model. Our literature search yielded 9266 articles on CLZ; among these, we identified 59 pertinent pharmacogenetic studies. Genotype data were retrieved for 14 polymorphisms in 9 genes. Among these, we had available data from at least three independent samples for 8 SNPs in 6 genes to perform meta-analyses: DRD2 rs1799732, DRD3 rs6280, HTR2A rs6313, rs6311, rs6314, HTR2C rs6318, HTR3A rs1062613, TNFa rs1800629. Although literature review provided conflicting results, in meta-analyses three genetic variants within serotonin genes resulted associated to CLZ response: rs6313 and rs6314 within HTR2A gene and rs1062613 within HT3A gene. On the other hand, no clear finding emerged for CLZ-induced weight gain. Our results suggest a possible serotonergic modulation of CLZ clinical response. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Fractality Evidence and Long-Range Dependence on Capital Markets: a Hurst Exponent Evaluation

NASA Astrophysics Data System (ADS)

Oprean, Camelia; Tănăsescu, Cristina

2014-07-01

Since the existence of market memory could implicate the rejection of the efficient market hypothesis, the aim of this paper is to find any evidence that selected emergent capital markets (eight European and BRIC markets, namely Hungary, Romania, Estonia, Czech Republic, Brazil, Russia, India and China) evince long-range dependence or the random walk hypothesis. In this paper, the Hurst exponent as calculated by R/S fractal analysis and Detrended Fluctuation Analysis is our measure of long-range dependence in the series. The results reinforce our previous findings and suggest that if stock returns present long-range dependence, the random walk hypothesis is not valid anymore and neither is the market efficiency hypothesis.

Association of RBP4 genetic variants with childhood obesity and cardiovascular risk factors.

PubMed

Codoñer-Franch, Pilar; Carrasco-Luna, Joaquín; Allepuz, Paula; Codoñer-Alejos, Alan; Guillem, Vicent

2016-12-01

Recent data suggest that retinol-binding protein 4 (RBP4) gene variants could be associated with a risk of obesity and its co-morbidities, such as metabolic syndrome, which increases the risk of developing type 2 diabetes mellitus and cardiovascular disease. The present study examined the potential association of RBP4 single nucleotide polymorphisms (SNPs) with childhood obesity and its metabolic complications. Four RBP4 SNPs, rs3758538 (3944A>C), rs3758539 (4406G>A), rs12265684 (12177G>C) and rs34571439 (14684T>G), were genotyped in a population of 180 Spanish Caucasian children (97 obese and 83 normal-weight children). Association of RBP4 SNPs with obesity, metabolic risk factors (blood pressure, triglycerides, high-density lipoprotein cholesterol, insulin resistance) and markers of vascular inflammation, such as high-sensitive C-reactive protein (hs-CRP), was tested. We found SNP rs3758538 to be associated with obesity (p = 0.007). Specifically, each copy of the minor allele C was associated with an increased risk of obesity, by more than twofold, in respect of being homozygous for the major allele A (odds ratio = 2.4; 95% confidence interval = 1.2-4.8). The rs3758538 and rs34571439 RBP4 SNPs correlated with plasma RBP4 levels. The SNPs rs12265684 and rs34571439 correlated with plasma triglyceride levels. The rs34571439 was also associated to hs-CRP levels. Marginal association of RBP4 SNPs with plasma high-density lipoprotein levels (rs34571439), blood pressure (rs12265684) and insulin resistance (rs3758539) was also observed. These findings suggest that childhood obesity may be associated with variations in RBP4 gene. The presence of selective SNPs in the RBP4 gene may account for metabolic complications. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The gustin (CA6) gene polymorphism, rs2274333 (A/G), as a mechanistic link between PROP tasting and fungiform taste papilla density and maintenance.

PubMed

Melis, Melania; Atzori, Elena; Cabras, Stefano; Zonza, Andrea; Calò, Carla; Muroni, Patrizia; Nieddu, Mariella; Padiglia, Alessandra; Sogos, Valeria; Tepper, Beverly J; Tomassini Barbarossa, Iole

2013-01-01

Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli.

Efficacy of ATR inhibitors as single agents in Ewing sarcoma

PubMed Central

Lecona, Emilio; Murga, Matilde; Callen, Elsa; Azorin, Daniel; Alonso, Javier; Lopez, Andres J.; Nussenzweig, Andre; Fernandez-Capetillo, Oscar

2016-01-01

Ewing sarcomas (ES) are pediatric bone tumors that arise from a driver translocation, most frequently EWS/FLI1. Current ES treatment involves DNA damaging agents, yet the basis for the sensitivity to these therapies remains unknown. Oncogene-induced replication stress (RS) is a known source of endogenous DNA damage in cancer, which is suppressed by ATR and CHK1 kinases. We here show that ES suffer from high endogenous levels of RS, rendering them particularly dependent on the ATR pathway. Accordingly, two independent ATR inhibitors show in vitro toxicity in ES cell lines as well as in vivo efficacy in ES xenografts as single agents. Expression of EWS/FLI1 or EWS/ERG oncogenic translocations sensitizes non-ES cells to ATR inhibitors. Our data shed light onto the sensitivity of ES to genotoxic agents, and identify ATR inhibitors as a potential therapy for Ewing Sarcomas. PMID:27577084

Relation between pretransplant serum levels of soluble CD30 and acute rejection during the first 6 months after a kidney transplant.

PubMed

Shooshtarizadeh, Tina; Mohammadali, Ali; Ossareh, Shahrzad; Ataipour, Yousef

2013-06-01

The immunologic status of kidney allograft recipients affects transplant outcome. High levels of pretransplant serum soluble CD30 correlate with an increased risk of acute rejection. Studies show conflicting results. We evaluated the relation between pretransplant serum sCD30 levels with the risk of posttransplant acute kidney rejection in renal transplant recipients. This prospective cohort study was performed between March 2010 and March 2011 on 77 kidney transplant recipients (53 men [68.8%], 24 women [31.2%]; mean age, 41 ± 14 y). Serum samples were collected 24 hours before transplant and analyzed for soluble CD30 levels by enzyme-linked immunosorbent assay. Patients were followed for 6 months after transplant. Acute biopsy-proven rejection episodes were recorded, serum creatinine levels were measured, and glomerular filtration rates were calculated at the first and sixth months after transplant. Preoperative serum soluble CD30 levels were compared in patients with and without rejection. The mean pretransplant serum soluble CD30 level was 92.1 ± 47.3 ng/mL. At 6 months' follow-up, 10 patients experienced acute rejection. Mean pretransplant soluble CD30 levels were 128.5 ± 84 ng/mL versus 86.7 ± 37 ng/mL in patients with and without acute rejection episodes (P = .008). At 100 ng/mL, the sensitivity, specificity, and positive and negative predictive values of pretransplant serum soluble CD30 level to predict acute rejection were 70%, 73.6%, 29.1%, and 94.3%. We showed a significant relation between pretransplant serum soluble CD30 levels and acute allograft rejection. High pretransplant levels of serum soluble CD30 can be a risk factor for kidney transplant rejection, and its high negative predictive value at various cutoffs make it useful to find candidates with a low risk of acute rejection after transplant.

Tumor margin assessment in Mohs surgery using reflectance, fluorescence and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Nguyen, Hieu T. M.; Moy, Austin J.; Zhang, Yao; Feng, Xu; Reichenberg, Jason S.; Fox, Matthew; Tunnell, James W.

2017-02-01

Mohs surgery is the current gold standard to treat large, aggressive or high-risk non-melanoma skin cancer (NMSC) cases. While Mohs surgery is an effective treatment, the procedure is time-consuming and expensive for physicians as well as burdensome for patients as they wait for frozen section histology. Our group has recently demonstrated high diagnostic accuracy using a noninvasive "spectral biopsy" (combination of diffuse reflectance (DRS), fluorescence (FS) and Raman spectroscopy (RS)) to classify NMSC vs. normal lesion in a screening setting of intact tissue. Here, we examine the sensitivity of spectral biopsy to pathology in excised Mohs sections. The system is designed with three modalities integrated into one fiber probe, which is utilized to measure DRS, FS, and RS of freshly excised skin from patients with various NMSC pathologies including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), where each measurement location is correlated to histopathology. The spectral biopsy provides complimentary physiological information including the reduced scattering coefficient, hemoglobin content and oxygen saturation from DRS, NADH and collagen contribution from FS and information regarding multiple proteins and lipids from RS. We then apply logistic regression model to the extracted physiological parameters to classify NMSC vs. normal tissue. The results on the excised tissue are generally consistent with in vivo measurements showing decreased scattering within the tumor and reduced fluorescence. Due to the high sensitivity of RS to lipids, subcutaneous fat often dominates the RS signal. This pilot study demonstrates the potential for a spectral biopsy to classify NMSC vs. normal tissue, indicating the opportunity to guide Mohs excisions.

Reliability, Validity and Treatment Sensitivity of the Schizophrenia Cognition Rating Scale

PubMed Central

Keefe, Richard S.E.; Davis, Vicki G.; Spagnola, Nathan B.; Hilt, Dana; Dgetluck, Nancy; Ruse, Stacy; Patterson, Thomas L.; Narasimhan, Meera; Harvey, Philip D.

2014-01-01

Cognitive functioning can be assessed with performance-based assessments such as neuropsychological tests and with interview-based assessments. Both assessment methods have the potential to assess whether treatments for schizophrenia improve clinically relevant aspects of cognitive impairment. However, little is known about the reliability, validity and treatment responsiveness of interview-based measures, especially in the context of clinical trials. Data from two studies were utilized to assess these features of the Schizophrenia Cognition Rating Scale (SCoRS). One of the studies was a validation study involving 79 patients with schizophrenia assessed at 3 academic research centers in the US. The other study was a 32-site clinical trial conducted in the US and Europe comparing the effects of encenicline, an alpha-7 nicotine agonist, to placebo in 319 patients with schizophrenia. The SCoRS interviewer ratings demonstrated excellent test-retest reliability in several different circumstances, including those that did not involve treatment (ICC> 0.90), and during treatment (ICC>0.80). SCoRS interviewer ratings were related to cognitive performance as measured by the MCCB (r= −0.35), and demonstrated significant sensitivity to treatment with encenicline compared to placebo (P<.001). These data suggest that the SCoRS has potential as a clinically relevant measure in clinical trials aiming to improve cognition in schizophrenia, and may be useful for clinical practice. The weaknesses of the SCoRS include its reliance on informant information, which is not available for some patients, and reduced validity when patient self-report is the sole information source. PMID:25028065

Reliability, validity and treatment sensitivity of the Schizophrenia Cognition Rating Scale.

PubMed

Keefe, Richard S E; Davis, Vicki G; Spagnola, Nathan B; Hilt, Dana; Dgetluck, Nancy; Ruse, Stacy; Patterson, Thomas D; Narasimhan, Meera; Harvey, Philip D

2015-02-01

Cognitive functioning can be assessed with performance-based assessments such as neuropsychological tests and with interview-based assessments. Both assessment methods have the potential to assess whether treatments for schizophrenia improve clinically relevant aspects of cognitive impairment. However, little is known about the reliability, validity and treatment responsiveness of interview-based measures, especially in the context of clinical trials. Data from two studies were utilized to assess these features of the Schizophrenia Cognition Rating Scale (SCoRS). One of the studies was a validation study involving 79 patients with schizophrenia assessed at 3 academic research centers in the US. The other study was a 32-site clinical trial conducted in the US and Europe comparing the effects of encenicline, an alpha-7 nicotine agonist, to placebo in 319 patients with schizophrenia. The SCoRS interviewer ratings demonstrated excellent test-retest reliability in several different circumstances, including those that did not involve treatment (ICC> 0.90), and during treatment (ICC>0.80). SCoRS interviewer ratings were related to cognitive performance as measured by the MCCB (r=-0.35), and demonstrated significant sensitivity to treatment with encenicline compared to placebo (P<.001). These data suggest that the SCoRS has potential as a clinically relevant measure in clinical trials aiming to improve cognition in schizophrenia, and may be useful for clinical practice. The weaknesses of the SCoRS include its reliance on informant information, which is not available for some patients, and reduced validity when patient's self-report is the sole information source. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

On the relationship between emotional state and abnormal unfairness sensitivity in alcohol dependence.

PubMed

Brevers, Damien; Noël, Xavier; Hanak, Catherine; Verbanck, Paul; Kornreich, Charles

2015-01-01

Recent empirical findings suggest that alcohol dependence is characterized by heightened sensitivity to unfairness during social transactions. The present study went a step further and aimed to ascertain whether this abnormal level of sensitivity to unfairness is underlined by an increased emotional reactivity. Twenty-six recently abstinent alcohol-dependent (AD) individuals and 32 controls performed an ultimatum game (UG), in which participants had to respond to take-it-or-leave-it offers, ranging from fair to unfair and made by a fictive proposer. Emotional state was recorded during UG offers presentation and was indexed by the amplitude of skin conductance response (SCR). Results showed that AD decided to reject unfair offers more frequently than their controls, confirming previous data. The proportion of rejected unfair UG offers was correlated with SCR, in the AD but not in the control group. This finding suggests that deciding to accept or reject unfair UG offers is influenced by arousal-affective activity in AD, but not in controls. Heightened emotional reactivity may have driven AD to punish the proposer rather than acting as a rational economic agent. An implication of present findings is that AD might have difficult to cope with unfair situations triggered by social interactions. Future studies are needed in order to examine whether-emotional and behavioral-reactivity to unfairness during the UG could impact alcohol consumption and relapse in AD.

Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward

PubMed Central

Henderson, Brandon J.; Wall, Teagan R.; Henley, Beverley M.; Kim, Charlene H.; Nichols, Weston A.; Moaddel, Ruin; Xiao, Cheng

2016-01-01

Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway. SIGNIFICANCE STATEMENT Menthol, the most popular flavorant for tobacco products, has been considered simply a benign flavor additive. However, as we show here, menthol alone exerts several neurobiological changes. We are among the first to show that menthol, by itself, increases the number of nicotinic acetylcholine receptors (nAChRs) in the mouse brain. It does so at a dose that matches nicotine in its ability to increase nAChR number. At this same dose, menthol also alters midbrain dopamine neuron function and prevents nicotine reward-related behavior. Together, our data show that menthol is more than an “inert” flavor additive and is able to change the function of midbrain dopamine neurons that are part of the mesolimbic reward pathway. PMID:26961950

Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.

PubMed

Vondran, Florian W R; Timrott, Kai; Kollrich, Sonja; Steinhoff, Ann-Kristin; Kaltenborn, Alexander; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank; Schwinzer, Reinhard

2014-09-01

Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF < BL < AR. Relying on serum analysis only, multivariate logistic regression (logit link function) yielded a prognostic score for prediction of rejection with 75.0% sensitivity and 69.2% specificity. Patients with rejection showed markedly higher pre-transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) Gene and Metabolic Risk Factors in the EPIC-Potsdam Study

PubMed Central

Arregui, Maria; Buijsse, Brian; Stefan, Norbert; Corella, Dolores; Fisher, Eva; di Giuseppe, Romina; Coltell, Oscar; Knüppel, Sven; Aleksandrova, Krasimira; Joost, Hans-Georg; Boeing, Heiner; Weikert, Cornelia

2012-01-01

Background Stearoyl-CoA desaturase-1 (SCD1) is an enzyme involved in lipid metabolism. In mice and humans its activity has been associated with traits of the metabolic syndrome, but also with the prevention of saturated fatty acids accumulation and subsequent inflammation, whereas for liver fat content inconsistent results have been reported. Thus, variants of the gene encoding SCD1 (SCD1) could potentially modify metabolic risk factors, but few human studies have addressed this question. Methods In a sample of 2157 middle-aged men and women randomly drawn from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1 tagging-single nucleotide polymorphisms (rs1502593, rs522951, rs11190480, rs3071, rs3793767, rs10883463 and rs508384) and 5 inferred haplotypes with frequency >5% describing 90.9% of the genotype combinations in our population, on triglycerides, body mass index (BMI), waist circumference (WC), glycated haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT) and fetuin-A. Results No significant associations between any of the SNPs or haplotypes and BMI, WC, fetuin-A and hs-CRP were observed. Associations of rs10883463 with triglycerides, GGT and HbA1c as well as of rs11190480 with ALT activity, were weak and became non-significant after multiple-testing correction. Also associations of the haplotype harbouring the minor allele of rs1502593 with HbA1c levels, the haplotype harbouring the minor alleles of rs11190480 and rs508384 with activity of ALT, and the haplotype harbouring the minor alleles of rs522951, rs10883463 and rs508384 with triglyceride and HbA1C levels and GGT activities did not withstand multiple-testing correction. Conclusion These findings suggest that there are no associations between common variants of SCD1 or its inferred haplotypes and the investigated metabolic risk factors. However, given the results from animal models, heterogeneity of human SCD1 warrants further investigation, in particular with regard to rare variants. PMID:23139775

Influence of Disturbance on Soil Respiration in Biologically Crusted Soil during the Dry Season

PubMed Central

Feng, Wei; Zhang, Yu-qing; Wu, Bin; Zha, Tian-shan; Jia, Xin; Qin, Shu-gao; Shao, Chen-xi; Liu, Jia-bin; Lai, Zong-rui; Fa, Ke-yu

2013-01-01

Soil respiration (Rs) is a major pathway for carbon cycling and is a complex process involving abiotic and biotic factors. Biological soil crusts (BSCs) are a key biotic component of desert ecosystems worldwide. In desert ecosystems, soils are protected from surface disturbance by BSCs, but it is unknown whether Rs is affected by disturbance of this crust layer. We measured Rs in three types of disturbed and undisturbed crusted soils (algae, lichen, and moss), as well as bare land from April to August, 2010, in Mu Us desert, northwest China. Rs was similar among undisturbed soils but increased significantly in disturbed moss and algae crusted soils. The variation of Rs in undisturbed and disturbed soil was related to soil bulk density. Disturbance also led to changes in soil organic carbon and fine particles contents, including declines of 60–70% in surface soil C and N, relative to predisturbance values. Once BSCs were disturbed, Q 10 increased. Our findings indicate that a loss of BSCs cover will lead to greater soil C loss through respiration. Given these results, understanding the disturbance sensitivity impact on Rs could be helpful to modify soil management practices which promote carbon sequestration. PMID:24453845

FABP4: a novel candidate gene for polycystic ovary syndrome.

PubMed

Wang, Jing; Tang, Jingwen; Wang, Binbin; Song, Junjie; Liu, Jingjing; Wei, Zhaolian; Zhang, Feng; Ma, Xu; Cao, Yunxia

2009-12-01

Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder involving a number of genetic and environmental factors. Adipocyte-fatty acid-binding protein (FABP4) is an adipokine regulating systemic insulin sensitivity, lipid and glucose metabolism. In humans serum FABP4 levels correlate significantly with features of PCOS. Previous researches showed strong evidences that FABP4 impacted the developing of PCOS possibly through its protein alteration or transcription regulation. Thus, the present study is the first attempt to identify the possible genetic role of FABP4 gene in the development of PCOS. About 1000 bp of the promoter region and four exons of FABP4 gene of 178 PCOS patients and 171 healthy controls were directly sequenced. Three polymorphisms, rs16909225, rs3834363, and rs16909220, were identified, of which rs16909225 and rs16909220 were completely linked (r² = 1) and not associated with the development of PCOS, while the -2-bp/-2-bp genotype of rs3834363 was significantly higher in PCOS than in the controls (χ² = 7.39, df = 1, P = 0.007, OR = 1.80 95% CI: 1.18-2.75). The present study is the first to establish an association between FABP4 gene polymorphisms and the development of PCOS.

One year results of preoperative single bolus ATG-Fresenius induction therapy in sensitized renal transplant recipients.

PubMed

Wang, D; Chen, J H; Wu, W Z; Yang, S L; Wu, G J; Wang, H; Tan, J M

2007-01-01

Sensitization in kidney transplantation is associated with more acute rejections, inferior graft survival, and an increase in delayed graft function. This study was designed to evaluate the efficacy and safety of preoperative single bolus antithymocyte globulin (ATG) induction therapy in sensitized renal transplant recipients. Fifty-six cadaveric donor kidney transplant recipients were divided into two groups: Group I (nonsensitized group, n = 30) and group II (sensitized group, PRA>10%, n = 26). ATG was given as a single preoperative bolus induction therapy to group II (ATG IV; 9 mg/kg). The group I patients were treated with mycophenolate mofetil preoperatively as induction therapy. The basic immunosuppressive regimen included tacrolimus (FK-506) or cyclosporine, mycophenolate mofetil, and prednisolone. After hospital discharge, patients were followed on a routine outpatient basis for 12 months. Acute rejection episodes (ARE) occurred in 20% (6/30) of group I and 15.38% (4/26) of group II patients (P = NS). Infections occurred in eight patients (26.7%) as 11 episodes (36.7%), averaging 1.4 episodes per infected patient in group 1, and 6 patients (23.1%) for a total of 10 episodes (38.5%), averaging 1.7 episodes per infected patient, in group II (P = NS). Occurrence of side effects and hospital stay were almost comparable in the two groups. No delayed graft function was observed in either group. The 12-month actuarial patient and graft survival were 100% in Group I and II. A preoperative single bolus ATG induction therapy was an effective and safe therapeutic measure, yielding an acceptable acute rejection rate in presensitized renal transplant recipients.

Genome-wide Linkage and Positional Association Study of Blood Pressure Response to Dietary Sodium Intervention

PubMed Central

Mei, Hao; Gu, Dongfeng; Hixson, James E.; Rice, Treva K.; Chen, Jing; Shimmin, Lawrence C.; Schwander, Karen; Kelly, Tanika N.; Liu, De-Pei; Chen, Shufeng; Huang, Jian-feng; Jaquish, Cashell E.; Rao, Dabeeru C.; He, Jiang

2012-01-01

The authors conducted a genome-wide linkage scan and positional association analysis to identify the genetic determinants of salt sensitivity of blood pressure (BP) in a large family-based, dietary-feeding study. The dietary intervention was conducted among 1,906 participants in rural China (2003–2005). A 7-day low-sodium intervention was followed by a 7-day high-sodium intervention. Salt sensitivity was defined as BP responses to low- and high-sodium interventions. Signals of the logarithm of the odds to the base 10 (LOD ≥ 3) were detected at 33–42 centimorgans of chromosome 2 (2p24.3-2p24.1), with a maximum LOD score of 3.33 for diastolic blood pressure responses to high-sodium intervention. LOD scores were 2.35–2.91 for mean arterial pressure (MAP) and 0.80–1.49 for systolic blood pressure responses in this region, respectively. Correcting for multiple tests, single nucleotide polymorphism (SNP) rs11674786 (2.7 kilobases upstream of the family with sequence similarity 84, member A, gene (FAM84A)) in the linkage region was significantly associated with diastolic blood pressure (P = 0.0007) and MAP responses (P = 0.0007), and SNP rs16983422 (2.8 kilobases upstream of the visinin-like 1 gene (VSNL1)) was marginally associated with diastolic blood pressure (P = 0.005) and MAP responses (P = 0.005). An additive interaction between SNPs rs11674786 and rs16983422 was observed, with P = 7.00 × 10−5 and P = 7.23 × 10−5 for diastolic blood pressure and MAP responses, respectively. The authors concluded that genetic region 2p24.3-2p24.1 might harbor functional variants for the salt sensitivity of BP. PMID:22865701

Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope.

PubMed

Tsai, Shang-Yi A; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-Fei; Xi, Zheng-Xiong; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

2015-11-24

The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.

Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

PubMed Central

Tsai, Shang-Yi A.; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-fei; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

2015-01-01

The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER–mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal. PMID:26554014

Interaction of CYP2C19, P2Y12, and GPIIIa Variants Associates With Efficacy of Clopidogrel and Adverse Events on Patients With Ischemic Stroke.

PubMed

Yi, Xingyang; Wang, Yanfen; Lin, Jing; Cheng, Wen; Zhou, Qiang; Wang, Chun

2017-10-01

Clopidogrel is a clinically important oral antiplatelet agent for the treatment or prevention of cerebrovascular disease. However, different individuals have different sensitivities to clopidogrel. This study assessed variants of different genes for association with response to clopidogrel, clinical outcome, and side effects in patients with ischemic stroke (IS). We consecutively enrolled 375 patients with IS after they received clopidogrel therapy, and venous blood samples were subjected to genotyping allelic variants of genes modulating clopidogrel absorption (ATP binding cassette subfamily B1, ABCB1), metabolic activation (cytochrome P450[CYP] 3A and CYP2C19), and biologic activity (platelet membrane receptor [ P2Y12, P2Y1)], and glycoprotein IIIa [ GPIIIa]) and statistically analyzing their interactions with clopidogrel sensitivity (CS) and adverse events, risk of IS recurrence, myocardial infarction, and death during 6 months of follow-up. Adverse events occurred in 37 patients (31 had IS recurrence, 4 died, and 2 had myocardial infarction) during the first 6 months of follow-up. Single locus analysis showed that only the CYP2C19*2(rs4244285) variant was independently associated with CS and risk of adverse events after adjusting covariates. However, there was significant gene-gene interaction among CYP2C19*2(rs4244285), P2Y12(rs16863323), and GPIIIa (rs2317676) analyzed by generalized multifactor dimensionality reduction methods. The rate of adverse events among patients with the 3-loci interaction was 2.82 times the rate among those with no interaction (95% confidence interval: 2.04-8.63). Sensitivity of patients with IS to clopidogrel and clopidogrel-induced adverse clinical events may be multifactorial but is not determined by single gene polymorphisms.

Comparison of gating dynamics of different IP3R channels with immune algorithm searching for channel parameter distributions

NASA Astrophysics Data System (ADS)

Cai, Xiuhong; Li, Xiang; Qi, Hong; Wei, Fang; Chen, Jianyong; Shuai, Jianwei

2016-10-01

The gating properties of the inositol 1, 4, 5-trisphosphate (IP3) receptor (IP3R) are determined by the binding and unbinding capability of Ca2+ ions and IP3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP3R (Oo-IP3R1), type-3 IP3R (Oo-IP3R3) and Spodoptera frugiperda IP3R (Sf-IP3R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP3Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model. By comparing the fitting parameter distributions of three IP3Rs, we suggest that the three types of IP3Rs have the similar open sensitivity in responding to IP3. The Oo-IP3R3 channel is easy to open in responding to low Ca2+ concentration, while Sf-IP3R channel is easily inhibited in responding to high Ca2+ concentration. We also show that the IP3 binding rate is not a sensitive parameter for stationary gating dynamics for three IP3Rs, but the inhibitory Ca2+ binding/unbinding rates are sensitive parameters for gating dynamics for both Oo-IP3R1 and Oo-IP3R3 channels. Such differences may be important in generating the spatially and temporally complex Ca2+ oscillations in cells. Our study also demonstrates that the immune algorithm can be applied for model parameter searching in biological systems.

Controlling Factors of Soil CO2 Efflux in Pinus yunnanensis across Different Stand Ages

PubMed Central

Wang, Shaojun; Zhao, Jixia; Chen, Qibo

2015-01-01

The characteristics of soil respiration (Rs) across different stand ages have not been well investigated. In this study, we identified temporal variation of Rs and its driving factors under three nature forest stands (e.g. 15-yr-old, 30-yr-old, and 45-yr-old) of Pinus yunnanensis in the Plateau of Mid-Yunnan, China. No consistent tendency was found on the change of Rs with the stand ages. Rs was ranked in the order of 30-yr-old > 45-yr-old >15-yr-old. Rs in 15-yr-old stand was the most sensitive to soil temperature (Ts) among the three sites. However, Ts only explained 30-40% of the seasonal dynamics of Rs at the site. Soil water content (Sw) was the major controlling factor of temporal variation at the three sites. Sw explained 88-93% of seasonal variations of Rs in the 30-yr-old stand, and 63.7-72.7% in the 15-yr-old and 79.1-79.6% in the 45-yr-old stands. In addition, we found that pH, available nitrogen (AN), C/N and total phosphorus (TP) contributed significantly to the seasonal variation of Rs. Sw was significantly related with pH, total nitrogen (TN), AN and TP, suggesting that Sw can affect Rs through improving soil acid-base property and soil texture, and increasing availability of soil nutrient. The results indicated that besides soil water, soil properties (e. g. pH, AN, C/N and TP) were also the important in controlling the temporal variations of Rs across different stand ages in the nature forestry. PMID:25996943

Influence of variation in the catechol-O-methyltransferase gene on the clinical outcome after lumbar spine surgery for one-level symptomatic disc disease: a report on 176 cases.

PubMed

Rut, Marcin; Machoy-Mokrzyńska, Anna; Ręcławowicz, Daniel; Słoniewski, Paweł; Kurzawski, Mateusz; Droździk, Marek; Safranow, Krzysztof; Morawska, Michalina; Białecka, Monika

2014-02-01

This study was aimed at the evaluation of the relationship between genetic polymorphisms of catechol-O-methyltransferase (COMT) (rs4680:A > G-Val158Met, rs6269:A > G, rs4633:C > T, rs4818:C > G) and pain sensitivity after lumbar discectomy. All patients had one-level symptomatic disc herniation from L3 to S1. The primary data recorded included visual analogue pain scales assessing back and leg pain, Oswestry Disability Questionnaire assessing quality of life and pain intensity, received/filled pre- and postoperatively. Each subject was genotyped for single-nucleotide polymorphism in the COMT gene. Clinical outcome was measured by difference between pre- and postoperative values and those results were analyzed with genetics findings. Pain intensity was associated with the COMT polymorphism. Carriers of rs6269 AA, rs4633 TT, rs4818 CC, and rs4680 AA genotypes were characterized by the lowest preoperative scores related to pain intensity and lower pain intensity at 1 year after the surgery. The rs4633 CC, rs4680 GG genotypes demonstrated significant clinical improvement in VASBACK score at 1 year after the surgery. Patients with COMT haplotype associated with low metabolic activity of enzyme (A_C_C_G) showed better clinical outcome measured by ODI score and VASBACK score 1 year after surgery. We did not observe any significant correlation between leg pain and single-nucleotide polymorphisms in the COMT gene. The results of our study indicate that polymorphism in the COMT gene may play an important role in the mechanism of pain perception, which may have a potential implication for clinical decision-making in the future.

Receptor protection studies comparing recombinant and native nicotinic receptors: Evidence for a subpopulation of mecamylamine-sensitive native alpha3beta4* nicotinic receptors.

PubMed

Free, R Benjamin; Kaser, Daniel J; Boyd, R Thomas; McKay, Dennis B

2006-01-09

Studies involving receptor protection have been used to define the functional involvement of specific receptor subtypes in tissues expressing multiple receptor subtypes. Previous functional studies from our laboratory demonstrate the feasibility of this approach when applied to neuronal tissues expressing multiple nicotinic acetylcholine receptors (nAChRs). In the current studies, the ability of a variety of nAChR agonists and antagonists to protect native and recombinant alpha3beta4 nAChRs from alkylation were investigated using nAChR binding techniques. Alkylation of native alpha3beta4* nAChRs from membrane preparations of bovine adrenal chromaffin cells resulted in a complete loss of specific [(3)H]epibatidine binding. This loss of binding to native nAChRs was preventable by pretreatment with the agonists, carbachol or nicotine. The partial agonist, cytisine, produced partial protection. Several nAChR antagonists were also tested for their ability to protect. Hexamethonium and decamethonium were without protective activity while mecamylamine and tubocurarine were partially effective. Addition protection studies were performed on recombinant alpha3beta4 nAChRs. As with native alpha3beta4* nAChRs, alkylation produced a complete loss of specific [(3)H]epibatidine binding to recombinant alpha3beta4 nAChRs which was preventable by pretreatment with nicotine. However, unlike native alpha3beta4* nAChRs, cytisine and mecamylamine, provide no protection for alkylation. These results highlight the differences between native alpha3beta4* nAChRs and recombinant alpha3beta4 nAChRs and support the use of protection assays to characterize native nAChR subpopulations.

Negative incidental emotions augment fairness sensitivity.

PubMed

Liu, Cuizhen; Chai, Jing Wen; Yu, Rongjun

2016-04-22

Previous studies have shown that task-unrelated emotions induced incidentally exert carryover effects on individuals' subsequent decisions in financial negotiations. However, the specificity of these emotion effects are not clear. In three experiments, we systematically investigated the role of seven transiently induced basic emotions (disgust, sadness, anger, fear, happiness, surprise and neutral) on rejection of unfair offers using the ultimatum game. We found that all negative emotions (disgust, sadness, anger and fear), but not happiness or surprise, significantly increased rejection rates, suggesting that the effect of incidental negative emotions on fairness is not specific to the type of negative emotion. Our findings highlight the role of fleeting emotions in biasing decision-making processes and suggest that all incidental negative emotions exert similar effects on fairness sensitivity, possibly by potentiating attention towards negative aspects of the situation.

Low-order aberration sensitivity of eighth-order coronagraph masks

NASA Technical Reports Server (NTRS)

Shaklan, Stuart B.; Green, Joseph J.

2005-01-01

In a recent paper, Kuchner, Crepp, and Ge describe new image-plane coronagraph mask designs that reject to eighth order the leakage of starlight caused by image motion at the mask, resulting in a substantial relaxation of image centroiding requirements compared to previous fourth-order and second-order masks. They also suggest that the new masks are effective at rejecting leakage caused by low-order aberrations (e.g., focus, coma, and astigmatism). In this paper, we derive the sensitivity of eighth-order masks to aberrations of any order and provide simulations of coronagraph behavior in the presence of optical aberrations.We find that the masks leak light as the fourth power of focus, astigmatism, coma, and trefoil. This has tremendous performance advantages for the Terrestrial Planet Finder Coronagraph.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biassoni, M.; Brofferio, C.; Bucci, C.

Due to their excellent energy resolution values and the vast choice of possible materials, bolometric detectors are currently widely used in the physics of rare events. A limiting aspect for bolometers rises from their inability to discriminate among radiation types or surface from bulk events. It has been demonstrated that the main limitation to sensitivity for purely bolometric detectors is represented by surface alpha contaminations, causing a continuous background that cannot be discriminated. A new scintillation based technique for the rejection of surface alpha background in non- scintillating bolometric experiments is proposed in this work. The idea is to combinemore » a scintillating and a high sensitivity photon detector with a non- scintillating absorber. Finally, we present results showing the possibility to reject events due to alpha decay at or nearby the surface of the crystal.« less

Parental punishment and peer victimization as developmental precursors to physical dating violence involvement among girls

PubMed Central

Hipwell, Alison E.; Stepp, Stephanie D.; Xiong, Shuangyan; Keenan, Kate; Blokland, Arjan; Loeber, Rolf

2012-01-01

The current study examined harsh punishment and peer victimization as developmental precursors to girls’ involvement in physical dating violence (PDV), and the putative mediating effect of rejection sensitivity. The sample comprised 475 African American and European American participants of the longitudinal Pittsburgh Girls Study who were dating at age 17. About 10% of girls reported significant perpetration and/or victimization of physical aggression in the relationship. Results showed that initial level and escalation in harsh punishment (between 10–13 years) and escalation in peer victimization (10–15 years) predicted PDV involvement, but this relationship was not mediated by rejection sensitivity. The results highlight the need to consider the impact of early experience of different forms of aggression on girls’ risk for PDV involvement. PMID:24591807

Lessons from simultaneous measurements of soil respiration and net ecosystem exchange of CO2 in temperate forests

NASA Astrophysics Data System (ADS)

Renchon, A.; Pendall, E.

2017-12-01

Land-surface exchanges of CO2 play a key role in ameliorating or exacerbating climate change. The eddy-covariance method allows direct measurement of net ecosystem-atmosphere exchange of CO2 (NEE), but partitioning daytime NEE into its components - gross primary productivity (GPP) and ecosystem respiration (RE) - remains challenging. Continuous measurements of soil respiration (RS), along with flux towers, have the potential to better constrain data and models of RE and GPP. We use simultaneous half-hourly NEE and RS data to: (1) compare the short-term (fortnightly) apparent temperature sensitivity (Q10) of nighttime RS and RE; (2) assess whether daytime RS can be estimated using nighttime response functions; and (3) compare the long-term (annual) responses of nighttime RS and nighttime RE to interacting soil moisture and soil temperature. We found that nighttime RS has a lower short-term Q10 than nighttime RE. This suggests that the Q10 of nighttime RE is strongly influenced by the Q10 of nighttime above-ground respiration, or possibly by a bias in RE measurements. The short-term Q10 of RS and RE decreased with increasing temperature. In general, daytime RS could be estimated using nighttime RS temperature and soil moisture (r2 = 0.9). However, this results from little to no diurnal variation in RS, and estimating daytime RS as the average of nighttime RS gave similar results (r2 = 0.9). Furthermore, we observed a day-night hysteresis of RS response to temperature, especially when using air temperature and sometimes when using soil temperature at 5cm depth. In fact, during some months, soil respiration observations were lower during daytime compared to nighttime, despite higher temperature in daytime. Therefore, daytime RS modelled from nighttime RS temperature response was overestimated during these periods. RS and RE responses to the combination of soil moisture and soil temperature were similar, and consistent with the DAMM model of soil-C decomposition. These findings underscore the value of continuous measurements of RS in flux tower footprints. Findings are also relevant to recent research on light inhibition of leaf respiration and contribute to improved understanding of ecosystem carbon cycle - climate feedback processes.

A non-invasive assessment of skin carotenoid status through reflection spectroscopy is a feasible, reliable and potentially valid measure of fruit and vegetable consumption in a diverse community sample.

PubMed

Jilcott Pitts, Stephanie Bell; Jahns, Lisa; Wu, Qiang; Moran, Nancy E; Bell, Ronny A; Truesdale, Kimberly P; Laska, Melissa N

2018-06-01

To assess the feasibility, reliability and validity of reflection spectroscopy (RS) to assess skin carotenoids in a racially diverse sample. Study 1 was a cross-sectional study of corner store customers (n 479) who completed the National Cancer Institute Fruit and Vegetable Screener as well as RS measures. Feasibility was assessed by examining the time it took to complete three RS measures, reliability was assessed by examining the variation between three RS measures, and validity was examined by correlation with self-reported fruit and vegetable consumption. In Study 2, validity was assessed in a smaller sample (n 30) by examining associations between RS measures and dietary carotenoids, fruits and vegetables as calculated from a validated FFQ and plasma carotenoids. Eastern North Carolina, USA. It took on average 94·0 s to complete three RS readings per person. The average variation between three readings for each participant was 6·8 %. In Study 2, in models adjusted for age, race and sex, there were statistically significant associations between RS measures and (i) FFQ-estimated carotenoid intake (P<0·0001); (ii) FFQ-estimated fruit and vegetable consumption (P<0·010); and (iii) plasma carotenoids (P<0·0001). RS is a potentially improved method to approximate fruit and vegetable consumption among diverse participants. RS is portable and easy to use in field-based public health nutrition settings. More research is needed to investigate validity and sensitivity in diverse populations.

Dietary Resistant Starch Supplementation Increases High-Density Lipoprotein Particle Number in Pigs Fed a Western Diet.

PubMed

Rideout, Todd C; Harding, Scott V; Raslawsky, Amy; Rempel, Curtis B

2017-05-04

Resistant starch (RS) has been well characterized for its glycemic control properties; however, there is little consensus regarding the influence of RS on blood lipid concentrations and lipoprotein distribution and size. Therefore, this study aimed to characterize the effect of daily RS supplementation in a controlled capsule delivery on biomarkers of cardiovascular (blood lipids, lipoproteins) and diabetes (glucose, insulin) risk in a pig model. Twelve 8-week-old male Yorkshire pigs were placed on a synthetic Western diet and randomly divided into two groups (n = 6/group) for 30 days: (1) a placebo group supplemented with capsules containing unmodified pre-gelatinized potato starch (0 g/RS/day); and (2) an RS group supplemented with capsules containing resistant potato starch (10 g/RS/day). Serum lipids including total-cholesterol (C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides did not differ (p > 0.05) between the RS and placebo groups. Although the total numbers of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) particles were similar (p > 0.05) between the two groups, total high-density lipoprotein (HDL) particles were higher (+28%, p < 0.05) in the RS group compared with placebo, resulting from an increase (p < 0.05) in the small HDL subclass particles (+32%). Compared with the placebo group, RS supplementation lowered (p < 0.05) fasting serum glucose (-20%) and improved (p < 0.05) insulin resistance as estimated by Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) without a change in insulin. Additionally, total serum glucagon-like-peptide 1 (GLP-1) was higher (+141%, p < 0.05) following RS supplementation compared with placebo. This data suggests that in addition to the more well-characterized effect of RS intake in lowering blood glucose and improving insulin sensitivity, the consumption of RS may be beneficial in lipid management strategies by enhancing total HDL particle number.

Lysine-specific demethylase 1: an epigenetic regulator of salt-sensitive hypertension.

PubMed

Williams, Jonathan S; Chamarthi, Bindu; Goodarzi, Mark O; Pojoga, Luminita H; Sun, Bei; Garza, Amanda E; Raby, Benjamin A; Adler, Gail K; Hopkins, Paul N; Brown, Nancy J; Jeunemaitre, Xavier; Ferri, Claudio; Fang, Rui; Leonor, Thiago; Cui, Jinrui; Guo, Xiuqing; Taylor, Kent D; Ida Chen, Yii-Der; Xiang, Anny; Raffel, Leslie J; Buchanan, Thomas A; Rotter, Jerome I; Williams, Gordon H; Shi, Yujiang

2012-07-01

Hypertension (HTN) represents a complex heritable disease in which environmental factors may directly affect gene function via epigenetic mechanisms. The aim of this study was to test the hypothesis that dietary salt influences the activity of a histone-modifying enzyme, lysine-specific demethylase 1 (LSD-1), which in turn is associated with salt-sensitivity of blood pressure (BP). Animal and human studies were performed. Salt-sensitivity of LSD-1 expression was assessed in wild-type (WT) and LSD-1 heterozygote knockout (LSD-1(+/-)) mice. Clinical relevance was tested by multivariate associations between single-nuclear polymorphisms (SNPs) in the LSD-1 gene and salt-sensitivity of BP, with control of dietary sodium, in a primary African-American hypertensive cohort and two replication hypertensive cohorts (Caucasian and Mexican-American). LSD-1 expression was modified by dietary salt in WT mice with lower levels associated with liberal salt intake. LSD-1(+/-) mice expressed lower LSD-1 protein levels than WT mice in kidney tissue. Similar to LSD-1(+/-) mice, African-American minor allele carriers of two LSD-1 SNPs displayed greater change in systolic BP (SBP) in response to change from low to liberal salt diet (rs671357, P = 0.01; rs587168, P = 0.005). This association was replicated in the Hispanic (rs587168, P = 0.04) but not the Caucasian cohort. Exploratory analyses demonstrated decreased serum aldosterone concentrations in African-American minor allele carriers similar to findings in the LSD-1(+/-) mice, decreased α-EnaC expression in LSD-1(+/-) mice, and impaired renovascular responsiveness to salt loading in minor allele carriers. The results of this translational research study support a role for LSD-1 in the pathogenesis of salt-sensitive HTN.

Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

PubMed

Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

2014-08-01

Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; p<0.001), which significantly correlated to functional connectivity changes observed within the thalamus in relation to the thalamo-prefrontal network, and in the anterior cingulate cortex and insula in relation to the thalamo-parietal network. Enhanced pain sensitivity from spinal deafferentation correlated with functional connectivity changes within brain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

“I Didn’t Know It Existed Before You Called”: Protestant Clergy Experience, Education and Perceptions Regarding Genetics

PubMed Central

Ragsdale, Judy; Vaughn, Lisa; Grossoehme, Daniel

2015-01-01

Despite the intrinsic role religious/spiritual (hereafter, R/S) beliefs have in patient clinical decision-making and crisis coping, there is little research exploring the relationship that exists between clergy (professionals who provide R/S counsel and guidance) and genetic counseling patients. This qualitative, exploratory study was designed to explore Protestant clergy (N=8) perceptions of and experience with genetics-related issues. Data analysis revealed that a wide range of R/S perceptions regarding genetics-related issues exist within Protestantism, Protestant clergy have a basic understanding of genetic testing and conditions, and while directive counseling is inherent to Protestant clergy counseling, there appears to exist two opposing styles: unbiased and biased. Based on this information, there are two main implications for genetic counseling clinical practice. First, R/S assessments need to be increasingly implemented into genetic counseling sessions, so that the psychosocial needs of patients with specific R/S beliefs can be identified and addressed. An increase in R/S assessments may be accomplished by increased exposure in genetic counselor training, continuing education opportunities, and by establishing relationships with board-certified, professional chaplains. Second, genetic counselors can influence the genetic education and experience of clergy by raising awareness within their own R/S assemblies. Doing so can also serve to further educate genetic counselors in the R/S beliefs of their own traditions, thus increasing sensitivity, empathy and the quality of care provided. PMID:23054334

Validity of retrospective disease activity assessment in systemic lupus erythematosus.

PubMed

Arce-Salinas, A; Cardiel, M H; Guzmán, J; Alcocer-Varela, J

1996-05-01

To evaluate the validity of retrospective disease activity assessment derived from clinical charts. We prospectively evaluated 37 patients with systemic lupus erythematosus (SLE) in 90 visits using the SLE Disease Activity Index (SLEDAI), the Mexican SLEDAI (Mex-SLEDAI), and the Lupus Activity Criteria Count (LACC) indices. Routine clinical observations were written by rheumatologists blind to index scores. These notes were reviewed 2 years later to obtain retrospective index scores and their validity was assessed using prospective scores as the standard. Statistical analysis was by Spearman's rank correlation coefficient (rs), Wilcoxon matched pairs test, kappa statistic, and intraclass correlation coefficient (ri). We calculated the sensitivity and specificity of retrospective indices to detect active disease. Median retrospective scores were lower in all indices: SLEDAI (4 VS 2, p =0.004, RS = 0.68, ri = 0.30); Mex-SLEDAI (2 vs 1, p < 0.0003, rs = 0.79, ri = 0.31); and LACC (1 vs 1, p = 0.007, rs = 0.65, ri = 0.21). Used to detect active SLE, the retrospective SLEDAI had a sensitivity of 0.68 and a specificity of 0.86; corresponding values for the Mex-SLEDAI were 0.72 and 0.91, and for the LACC, 0.77 and 0.76. Retrospective disease activity indices tended to provide lower scores than prospective evaluations. They often missed patients with mildly active disease, but when positive they were good predictors of disease activity.

Blueberry antagonism of C-2 ceramide disruption of Ca2+ responses and recovery in MAChR-transfected COS-7 cells involves alterations in stress signaling

USDA-ARS?s Scientific Manuscript database

Muscarinic receptors (MAChRs) show loss of sensitivity in aging and AD, and are selectively sensitive to oxidative stress sensitivity (OSS), transfected (tn) with MAChR subtype M1 showing > OSS [the ability of the cell to extrude or sequester Ca2+ following depolarization (Recovery) by oxotremorine ...

Tropisetron sensitizes α7 containing nicotinic receptors to low levels of acetylcholine in vitro and improves memory-related task performance in young and aged animals.

PubMed

Callahan, Patrick M; Bertrand, Daniel; Bertrand, Sonia; Plagenhoef, Marc R; Terry, Alvin V

2017-05-01

Tropisetron, a 5-HT 3 receptor antagonist commonly prescribed for chemotherapy-induced nausea and vomiting also exhibits high affinity, partial agonist activity at α7 nicotinic acetylcholine receptors (α7 nAChRs). α7 nAChRs are considered viable therapeutic targets for neuropsychiatric disorders such as Alzheimer's disease (AD). Here we further explored the nAChR pharmacology of tropisetron to include the homomeric α7 nAChR and recently characterized heteromeric α7β2 nAChR (1:10 ratio) and we evaluated its cognitive effects in young and aged animals. Electrophysiological studies on human nAChRs expressed in Xenopus oocytes confirmed the partial agonist activity of tropisetron at α7 nAChRs (EC 50 ∼2.4 μM) with a similar effect at α7β2 nAChRs (EC 50 ∼1.5 μM). Moreover, currents evoked by irregular pulses of acetylcholine (40 μM) at α7 and α7β2 nAChRs were enhanced during sustained exposure to low concentrations of tropisetron (10 and 30 nM) indicative of a "priming" or co-agonist effect. Tropisetron (0.1-10 mg/kg) improved novel object recognition performance in young Sprague-Dawley rats and in aged Fischer rats. In aged male and female rhesus monkeys, tropisetron (0.03-1 mg/kg) produced a 17% increase from baseline levels in delayed match to sample long delay accuracy while combination of non-effective doses of donepezil (0.1 mg/kg) and tropisetron (0.03 and 0.1 mg/kg) produced a 24% change in accuracy. Collectively, these animal experiments indicate that tropisetron enhances cognition and has the ability to improve the effective dose range of currently prescribed AD therapy (donepezil). Moreover, these effects may be explained by tropisetron's ability to sensitize α7 containing nAChRs to low levels of acetylcholine. Copyright © 2017 Elsevier Ltd. All rights reserved.

SIRT1 genetic variants associate with the metabolic response of Caucasians to a controlled lifestyle intervention--the TULIP Study.

PubMed

Weyrich, Peter; Machicao, Fausto; Reinhardt, Julia; Machann, Jürgen; Schick, Fritz; Tschritter, Otto; Stefan, Norbert; Fritsche, Andreas; Häring, Hans-Ulrich

2008-11-12

Sirtuin1 (SIRT1) regulates gene expression in distinct metabolic pathways and mediates beneficial effects of caloric restriction in animal models. In humans, SIRT1 genetic variants associate with fasting energy expenditure. To investigate the relevance of SIRT1 for human metabolism and caloric restriction, we analyzed SIRT1 genetic variants in respect to the outcome of a controlled lifestyle intervention in Caucasians at risk for type 2 diabetes. A total of 1013 non-diabetic Caucasians from the Tuebingen Family Study (TUEF) were genotyped for four tagging SIRT1 SNPs (rs730821, rs12413112, rs7069102, rs2273773) for cross-sectional association analyses with prediabetic traits. SNPs that associated with basal energy expenditure in the TUEF cohort were additionally analyzed in 196 individuals who underwent a controlled lifestyle intervention (Tuebingen Lifestyle Intervention Program; TULIP). Multivariate regressions analyses with adjustment for relevant covariates were performed to detect associations of SIRT1 variants with the changes in anthropometrics, weight, body fat or metabolic characteristics (blood glucose, insulin sensitivity, insulin secretion and liver fat, measured by magnetic resonance techniques) after the 9-month follow-up test in the TULIP study. Minor allele (X/A) carriers of rs12413112 (G/A) had a significantly lower basal energy expenditure (p = 0.04) and an increased respiratory quotient (p = 0.02). This group (rs12413112: X/A) was resistant against lifestyle-induced improvement of fasting plasma glucose (GG: -2.01%, X/A: 0.53%; p = 0.04), had less increase in insulin sensitivity (GG: 17.3%, X/A: 9.6%; p = 0.05) and an attenuated decline in liver fat (GG: -38.4%, X/A: -7.5%; p = 0.01). SIRT1 plays a role for the individual lifestyle intervention response, possibly owing to decreased basal energy expenditure and a lower lipid-oxidation rate in rs12413112 X/A allele carriers. SIRT1 genetic variants may, therefore, represent a relevant determinant for the response rate of individuals undergoing caloric restriction and increased physical activity.

Induced pluripotent stem cell-derived gamete-associated proteins incite rejection of induced pluripotent stem cells in syngeneic mice.

PubMed

Kim, Eun-Mi; Manzar, Gohar; Zavazava, Nicholas

2017-06-01

The safety of induced pluripotent stem cells (iPSCs) in autologous recipients has been questioned after iPSCs, but not embryonic stem cells (ESCs), were reported to be rejected in syngeneic mice. This important topic has remained controversial because there has not been a mechanistic explanation for this phenomenon. Here, we hypothesize that iPSCs, but not ESCs, readily differentiate into gamete-forming cells that express meiotic antigens normally found in immune-privileged gonads. Because peripheral blood T cells are not tolerized to these antigens in the thymus, gamete-associated-proteins (GAPs) sensitize T cells leading to rejection. Here, we provide evidence that GAPs expressed in iPSC teratomas, but not in ESC teratomas, are responsible for the immunological rejection of iPSCs. Furthermore, silencing the expression of Stra8, 'the master regulator of meiosis', in iPSCs, using short hairpin RNA led to significant abrogation of the rejection of iPSCs, supporting our central hypothesis that GAPs expressed after initiation of meiosis in iPSCs were responsible for rejection. In contrast to iPSCs, iPSC-derivatives, such as haematopoietic progenitor cells, are able to engraft long-term into syngeneic recipients because they no longer express GAPs. Our findings, for the first time, provide a unifying explanation of why iPSCs, but not ESCs, are rejected in syngeneic recipients, ending the current controversy on the safety of iPSCs and their derivatives. © 2017 John Wiley & Sons Ltd.

Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection.

PubMed

Angaswamy, Nataraju; Tiriveedhi, Venkataswarup; Sarma, Nayan J; Subramanian, Vijay; Klein, Christina; Wellen, Jason; Shenoy, Surendra; Chapman, William C; Mohanakumar, T

2013-11-01

Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Photolabeling a Nicotinic Acetylcholine Receptor (nAChR) with an (α4)3(β2)2 nAChR-Selective Positive Allosteric Modulator

PubMed Central

Deba, Farah; Wang, Ze-Jun; Cohen, Jonathan B.

2016-01-01

Positive allosteric modulators (PAMs) of nicotinic acetylcholine (ACh) receptors (nAChRs) have potential clinical applications in the treatment of nicotine dependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity, and 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole (CMPI) has been identified as a PAM selective for neuronal nAChRs containing the α4 subunit. In this report, we compare CMPI interactions with low-sensitivity (α4)3(β2)2 and high-sensitivity (α4)2(β2)3 nAChRs, and with muscle-type nAChRs. In addition, we use the intrinsic reactivity of [3H]CMPI upon photolysis at 312 nm to identify its binding sites in Torpedo nAChRs. Recording from Xenopus oocytes, we found that CMPI potentiated maximally the responses of (α4)3(β2)2 nAChR to 10 μM ACh (EC10) by 400% and with an EC50 of ∼1 µM. CMPI produced a left shift of the ACh concentration-response curve without altering ACh efficacy. In contrast, CMPI inhibited (∼35% at 10 µM) ACh responses of (α4)2(β2)3 nAChRs and fully inhibited human muscle and Torpedo nAChRs with IC50 values of ∼0.5 µM. Upon irradiation at 312 nm, [3H]CMPI photoincorporated into each Torpedo [(α1)2β1γδ] nAChR subunit. Sequencing of peptide fragments isolated from [3H]CMPI-photolabeled nAChR subunits established photolabeling of amino acids contributing to the ACh binding sites (αTyr190, αTyr198, γTrp55, γTyr111, γTyr117, δTrp57) that was fully inhibitable by agonist and lower-efficiency, state-dependent [3H]CMPI photolabeling within the ion channel. Our results establish that CMPI is a potent potentiator of nAChRs containing an α4:α4 subunit interface, and that its intrinsic photoreactivy makes it of potential use to identify its binding sites in the (α4)3(β2)2 nAChR. PMID:26976945

Association Between the Estrogen Receptor Beta (ESR2) Rs1256120 Single Nucleotide Polymorphism and Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-Analysis.

PubMed

Zhao, Linlu; Roffey, Darren M; Chen, Suzan

2017-06-01

A systematic review and meta-analysis. The aim of this study was to assess and synthesize the current evidence on the association between the rs1256120 single nucleotide polymorphism (SNP) of the estrogen receptor beta gene (ESR2) and adolescent idiopathic scoliosis (AIS). Hormonal disturbance has been postulated as a potential etiological factor in the development of AIS. As estrogen receptors are important mediators of estrogen response, mutations in these genes, including rs1256120 of ESR2, have been chosen as susceptibility candidates for AIS predisposition. The association of rs1256120 with AIS has been investigated in several recent studies, but showed conflicting evidence. We conducted a systematic review to evaluate the strength of this body of evidence and quantitative synthesis to examine sources of heterogeneity. This study conformed to PRISMA guidelines. Using a sensitive search strategy, PubMed (MEDLINE), EMBASE, and HuGE Literature Finder databases were searched to identify relevant studies for inclusion in the systematic review and meta-analysis. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. The inverse variance model was used to calculate summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the allelic (C vs. T) and genotypic comparisons. Planned subgroup and sensitivity analyses were performed. Three studies were included for systematic review and meta-analysis (n = 1264 AIS cases and n=1020 controls). A null relationship was found between rs1256120 and AIS (allelic OR = 1.20, 95% CI: 0.81-1.78, P = 0.36, I = 84.9%), with the first reported association likely to be false-positive and contributing substantially to heterogeneity. Findings from the systematic review and meta-analysis suggest that rs1256120 of ESR2 is unlikely to be a predisposing or disease-modifying genetic risk factor for AIS. 2.

Active disturbance rejection controller for chemical reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Both, Roxana; Dulf, Eva H.; Muresan, Cristina I., E-mail: roxana.both@aut.utcluj.ro

2015-03-10

In the petrochemical industry, the synthesis of 2 ethyl-hexanol-oxo-alcohols (plasticizers alcohol) is of high importance, being achieved through hydrogenation of 2 ethyl-hexenal inside catalytic trickle bed three-phase reactors. For this type of processes the use of advanced control strategies is suitable due to their nonlinear behavior and extreme sensitivity to load changes and other disturbances. Due to the complexity of the mathematical model an approach was to use a simple linear model of the process in combination with an advanced control algorithm which takes into account the model uncertainties, the disturbances and command signal limitations like robust control. However themore » resulting controller is complex, involving cost effective hardware. This paper proposes a simple integer-order control scheme using a linear model of the process, based on active disturbance rejection method. By treating the model dynamics as a common disturbance and actively rejecting it, active disturbance rejection control (ADRC) can achieve the desired response. Simulation results are provided to demonstrate the effectiveness of the proposed method.« less

Genetically modified porcine split-thickness skin grafts as an alternative to allograft for provision of temporary wound coverage: preliminary characterization.

PubMed

Leto Barone, Angelo A; Mastroianni, Melissa; Farkash, Evan A; Mallard, Christopher; Albritton, Alexander; Torabi, Radbeh; Leonard, David A; Kurtz, Josef M; Sachs, David H; Cetrulo, Curtis L

2015-05-01

Temporary coverage of severely burned patients with cadaver allograft skin represents an important component of burn care, but is limited by availability and cost. Porcine skin shares many physical properties with human skin, but is susceptible to hyperacute rejection due to preformed antibodies to α-1,3-galactose (Gal), a carbohydrate on all porcine cells. Our preliminary studies have suggested that skin grafts from α-1,3-galactosyltransferase knock out (GalT-KO) miniature swine might provide temporary wound coverage comparable to allografts, since GalT-KO swine lack this carbohydrate. To further evaluate this possibility, eight non-human primates received primary autologous, allogeneic, GalT-KO, and GalT+xenogeneic skin grafts. Additionally, secondary grafts were placed to assess whether sensitization would affect the rejection time course of identical-type grafts. We demonstrate that both GalT-KO xenografts and allografts provide temporary coverage of partial- and full-thickness wounds for up to 11 days. In contrast, GalT+xenografts displayed hyperacute rejection, with no signs of vascularization and rapid avulsion from wounds. Furthermore, secondary GalT-KO transplants failed to vascularize, demonstrating that primary graft rejection sensitizes the recipient. We conclude that GalT-KO xenografts may provide temporary coverage of wounds for a duration equivalent to allografts, and thus, could serve as a readily available alternative treatment of severe burns. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Biochar-based constructed wetlands to treat reverse osmosis rejected concentrates in chronic kidney disease endemic areas in Sri Lanka.

PubMed

Athapattu, B C L; Thalgaspitiya, T W L R; Yasaratne, U L S; Vithanage, Meththika

2017-12-01

The objectives were to investigate the potential remedial measures for reverse osmosis (RO) rejected water through constructed wetlands (CWs) with low-cost materials in the media established in chronic kidney disease of unknown etiology (CKDu) prevalent area in Sri Lanka. A pilot-scale surface and subsurface water CWs were established at the Medawachchiya community-based RO water supply unit. Locally available soil, calicut tile and biochar were used in proportions of 81, 16.5 and 2.5% (w/w), respectively, as filter materials in the subsurface. Vetiver grass and Scirpus grossus were selected for subsurface wetland while water lettuce and water hyacinth were chosen for free water surface CWs. Results showed that the CKDu sensitive parameters; total dissolved solids, hardness, total alkalinity and fluoride were reduced considerably (20-85%) and most met desirable levels of stipulated ambient standards. Biochar seemed to play a major role in removing fluoride from the system which may be due to the existing and adsorbed K + , Ca +2 , Mg +2 , etc. on the biochar surface via chemisorption. The least reduction was observed for alkalinity. This study indicated potential purification of aforesaid ions in water which are considerably present in RO rejection. Therefore, the invented bio-geo constructed wetland can be considered as a sustainable, economical and effective option for reducing high concentrations of CKDu sensitive parameters in RO rejected water before discharging into the inland waters.

BDNF rs6265 methylation and genotype interact on risk for schizophrenia.

PubMed

Ursini, Gianluca; Cavalleri, Tommaso; Fazio, Leonardo; Angrisano, Tiziana; Iacovelli, Luisa; Porcelli, Annamaria; Maddalena, Giancarlo; Punzi, Giovanna; Mancini, Marina; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Calabrese, Francesca; Rampino, Antonio; Taurisano, Paolo; Di Giorgio, Annabella; Keller, Simona; Tarantini, Letizia; Sinibaldi, Lorenzo; Quarto, Tiziana; Popolizio, Teresa; Caforio, Grazia; Blasi, Giuseppe; Riva, Marco A; De Blasi, Antonio; Chiariotti, Lorenzo; Bollati, Valentina; Bertolino, Alessandro

2016-01-01

Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes.

Multilocus family-based association analysis of seven candidate polymorphisms with essential hypertension in an african-derived semi-isolated brazilian population.

PubMed

Kimura, L; Angeli, C B; Auricchio, M T B M; Fernandes, G R; Pereira, A C; Vicente, J P; Pereira, T V; Mingroni-Netto, R C

2012-01-01

Background. It has been widely suggested that analyses considering multilocus effects would be crucial to characterize the relationship between gene variability and essential hypertension (EH). Objective. To test for the presence of multilocus effects between/among seven polymorphisms (six genes) on blood pressure-related traits in African-derived semi-isolated Brazilian populations (quilombos). Methods. Analyses were carried out using a family-based design in a sample of 652 participants (97 families). Seven variants were investigated: ACE (rs1799752), AGT (rs669), ADD2 (rs3755351), NOS3 (rs1799983), GNB3 (rs5441 and rs5443), and GRK4 (rs1801058). Sensitivity analyses were further performed under a case-control design with unrelated participants only. Results. None of the investigated variants were associated individually with both systolic and diastolic BP levels (SBP and DBP, respectively) or EH (as a binary outcome). Multifactor dimensionality reduction-based techniques revealed a marginal association of the combined effect of both GNB3 variants on DBP levels in a family-based design (P = 0.040), whereas a putative NOS3-GRK4 interaction also in relation to DBP levels was observed in the case-control design only (P = 0.004). Conclusion. Our results provide limited support for the hypothesis of multilocus effects between/among the studied variants on blood pressure in quilombos. Further larger studies are needed to validate our findings.

Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection.

PubMed

Gregson, Aric L; Hoji, Aki; Injean, Patil; Poynter, Steven T; Briones, Claudia; Palchevskiy, Vyacheslav; Weigt, S Sam; Shino, Michael Y; Derhovanessian, Ariss; Sayah, David; Saggar, Rajan; Ross, David; Ardehali, Abbas; Lynch, Joseph P; Belperio, John A

2015-12-15

The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes. To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence. Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed. AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets. Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation.

Altered Exosomal RNA Profiles in Bronchoalveolar Lavage from Lung Transplants with Acute Rejection

PubMed Central

Hoji, Aki; Injean, Patil; Poynter, Steven T.; Briones, Claudia; Palchevskiy, Vyacheslav; Sam Weigt, S.; Shino, Michael Y.; Derhovanessian, Ariss; Saggar, Rajan; Ross, David; Ardehali, Abbas; Lynch, Joseph P.; Belperio, John A.

2015-01-01

Rationale: The mechanism by which acute allograft rejection leads to chronic rejection remains poorly understood despite its common occurrence. Exosomes, membrane vesicles released from cells within the lung allograft, contain a diverse array of biomolecules that closely reflect the biologic state of the cell and tissue from which they are released. Exosome transcriptomes may provide a better understanding of the rejection process. Furthermore, biomarkers originating from this transcriptome could provide timely and sensitive detection of acute cellular rejection (AR), reducing the incidence of severe AR and chronic lung allograft dysfunction and improving outcomes. Objectives: To provide an in-depth analysis of the bronchoalveolar lavage fluid exosomal shuttle RNA population after lung transplantation and evaluate for differential expression between acute AR and quiescence. Methods: Serial bronchoalveolar lavage specimens were ultracentrifuged to obtain the exosomal pellet for RNA extraction, on which RNA-Seq was performed. Measurements and Main Results: AR demonstrates an intense inflammatory environment, skewed toward both innate and adaptive immune responses. Novel, potential upstream regulators identified offer potential therapeutic targets. Conclusions: Our findings validate bronchoalveolar lavage fluid exosomal shuttle RNA as a source for understanding the pathophysiology of AR and for biomarker discovery in lung transplantation. PMID:26308930

Zernike Wavefront Sensor Modeling Development for LOWFS on WFIRST-AFTA

NASA Technical Reports Server (NTRS)

Wang, Xu; Wallace, J. Kent; Shi, Fang

2015-01-01

WFIRST-AFTA design makes use of an existing 2.4m telescope for direct imaging of exoplanets. To maintain the high contrast needed for the coronagraph, wavefront error (WFE) of the optical system needs to be continuously sensed and controlled. Low Order Wavefront Sensing (LOWFS) uses the rejected starlight from an immediate focal plane to sense wavefront changes (mostly thermally induced low order WFE) by combining the LOWFS mask (a phase plate located at the small center region with reflective layer) with the starlight rejection masks, i.e. Hybrid Lyot Coronagraph (HLC)'s occulter or Shaped Pupil Coronagraph (SPC)'s field stop. Zernike wavefront sensor (ZWFS) measures phase via the phase-contrast method and is known to be photon noise optimal for measuring low order aberrations. Recently, ZWFS was selected as the baseline LOWFS technology on WFIST/AFTA for its good sensitivity, accuracy, and its easy integration with the starlight rejection mask. In this paper, we review the theory of ZWFS operation, describe the ZWFS algorithm development, and summarize various numerical sensitivity studies on the sensor performance. In the end, the predicted sensor performance on SPC and HLC configurations are presented.

Peer effects on self-regulation in adolescence depend on the nature and quality of the peer interaction.

PubMed

King, Kevin M; McLaughlin, Katie A; Silk, Jennifer; Monahan, Kathryn C

2017-11-21

Adolescence is a critical period for the development of self-regulation, and peer interactions are thought to strongly influence regulation ability. Simple exposure to peers has been found to alter decisions about risky behaviors and increase sensitivity to rewards. The link between peer exposure and self-regulation is likely to vary as a function of the type and quality of peer interaction (e.g., rejection or acceptance). Little is known about how the nature of interactions with peers influences different dimensions of self-regulation. We examined how randomization to acceptance or rejection by online "virtual" peers influenced multiple dimensions of self-regulation in a multisite community sample of 273 adolescents aged 16-17 years. Compared to a neutral condition, exposure to peers produced increases in cold cognitive control, but decreased hot cognitive control. Relative to peer acceptance, peer rejection reduced distress tolerance and increased sensitivity to losses. These findings suggest that different dimensions of adolescent self-regulation are influenced by the nature of the peer context: basic cognitive functions are altered by mere exposure to peers, whereas more complex decision making and emotion regulation processes are influenced primarily by the quality of that exposure.

Determinants of Prosocial Behavior in Included Versus Excluded Contexts

PubMed Central

Cuadrado, Esther; Tabernero, Carmen; Steinel, Wolfgang

2016-01-01

Prosocial behavior (PSB) is increasingly becoming necessary as more and more individuals experience exclusion. In this context it is important to understand the motivational determinants of PSB. Here we report two experiments which analyzed the influence of dispositional (prosocialness; rejection sensitivity) and motivational variables (prosocial self-efficacy; prosocial collective efficacy; trust; anger; social affiliation motivation) on PSB under neutral contexts (Study 1), and once under inclusion or exclusion conditions (Study 2). Both studies provided evidence for the predicted mediation of PSB. Results in both neutral and inclusion and exclusion conditions supported our predictive model of PSB. In the model dispositional variables predicted motivational variables, which in turn predicted PSB. We showed that the investigated variables predicted PSB; this suggests that to promote PSB one could (1) foster prosocialness, prosocial self and collective efficacy, trust in others and affiliation motivation and (2) try to reduce negative feelings and the tendency to dread rejection in an attempt to reduce the negative impact that these variables have on PSB. Moreover, the few differences that emerged in the model between the inclusion and exclusion contexts suggested that in interventions with excluded individuals special care emphasis should be placed on addressing rejection sensitivity and lack of trust. PMID:26779103

Determinants of Prosocial Behavior in Included Versus Excluded Contexts.

PubMed

Cuadrado, Esther; Tabernero, Carmen; Steinel, Wolfgang

2015-01-01

Prosocial behavior (PSB) is increasingly becoming necessary as more and more individuals experience exclusion. In this context it is important to understand the motivational determinants of PSB. Here we report two experiments which analyzed the influence of dispositional (prosocialness; rejection sensitivity) and motivational variables (prosocial self-efficacy; prosocial collective efficacy; trust; anger; social affiliation motivation) on PSB under neutral contexts (Study 1), and once under inclusion or exclusion conditions (Study 2). Both studies provided evidence for the predicted mediation of PSB. Results in both neutral and inclusion and exclusion conditions supported our predictive model of PSB. In the model dispositional variables predicted motivational variables, which in turn predicted PSB. We showed that the investigated variables predicted PSB; this suggests that to promote PSB one could (1) foster prosocialness, prosocial self and collective efficacy, trust in others and affiliation motivation and (2) try to reduce negative feelings and the tendency to dread rejection in an attempt to reduce the negative impact that these variables have on PSB. Moreover, the few differences that emerged in the model between the inclusion and exclusion contexts suggested that in interventions with excluded individuals special care emphasis should be placed on addressing rejection sensitivity and lack of trust.

Fragrant dioxane derivatives identify beta1-subunit-containing GABAA receptors.

PubMed

Sergeeva, Olga A; Kletke, Olaf; Kragler, Andrea; Poppek, Anja; Fleischer, Wiebke; Schubring, Stephan R; Görg, Boris; Haas, Helmut L; Zhu, Xin-Ran; Lübbert, Hermann; Gisselmann, Günter; Hatt, Hanns

2010-07-30

Nineteen GABA(A) receptor (GABA(A)R) subunits are known in mammals with only a restricted number of functionally identified native combinations. The physiological role of beta1-subunit-containing GABA(A)Rs is unknown. Here we report the discovery of a new structural class of GABA(A)R positive modulators with unique beta1-subunit selectivity: fragrant dioxane derivatives (FDD). At heterologously expressed alpha1betaxgamma2L (x-for 1,2,3) GABA(A)R FDD were 6 times more potent at beta1- versus beta2- and beta3-containing receptors. Serine at position 265 was essential for the high sensitivity of the beta1-subunit to FDD and the beta1N286W mutation nearly abolished modulation; vice versa the mutation beta3N265S shifted FDD sensitivity toward the beta1-type. In posterior hypothalamic neurons controlling wakefulness GABA-mediated whole-cell responses and GABAergic synaptic currents were highly sensitive to FDD, in contrast to beta1-negative cerebellar Purkinje neurons. Immunostaining for the beta1-subunit and the potency of FDD to modulate GABA responses in cultured hypothalamic neurons was drastically diminished by beta1-siRNA treatment. In conclusion, with the help of FDDs we reveal a functional expression of beta1-containing GABA(A)Rs in the hypothalamus, offering a new tool for studies on the functional diversity of native GABA(A)Rs.

Comparison of procalcitonin and different guidelines for first febrile urinary tract infection in children by imaging.

PubMed

Liao, Pei-Fen; Ku, Min-Sho; Tsai, Jeng-Dau; Choa, Yu-Hua; Hung, Tung-Wei; Lue, Ko-Huang; Sheu, Ji-Nan

2014-09-01

We examined the ability of a procalcitonin (PCT) protocol to detect vesicoureteral reflux (VUR) and renal scarring (RS), evaluated procedural costs and radiation burden, and compared four representative guidelines for children with their first febrile urinary tract infection (UTI). Children aged ≤2 years with their first febrile UTI who underwent renal ultrasonography (US), acute and late technetium-99m ((99m)Tc)-dimercaptosuccinic acid scan, and voiding cystourethrography were prospectively studied. The representative guidelines applied in a retrospective simulation included the American Academy of Pediatrics (AAP), National Institute of Clinical Excellence, top-down approach (TDA), and Italian Society of Pediatric Nephrology (ISPN). These were compared in terms of ability to detect abnormalities, procedural costs and radiation. Of 278 children analyzed, 172 (61.9%) had acute pyelonephritis. There was VUR in 101 (36.3%) children, including 73 (26.3%) with grades III-V VUR. RS was identified in 75 (27.0%) children. To detect VUR, TDA and PCT had the highest sensitivity for grades I-V VUR (80.2%) and III-V VUR (94.5%), respectively, whereas AAP had the highest specificity for I-V VUR (77.4%) and III-V VUR (78.0%), respectively. TDA and PCT had the highest sensitivity (100%) for detecting RS. The highest cost and radiation dose was associated with TDA, whereas AAP had the least expenditure and radiation exposure. By multivariate analysis, PCT and VUR, especially grades III-V, were independent predictors of RS. There is no perfect guideline for first febrile UTI children. The PCT protocol has good ability for detecting high-grade VUR and RS. If based on available imaging modalities and reducing cost and radiation burden, clinical suggestions in the AAP guidelines represent a considerable protocol.

Effects of wheat bran extract rich in arabinoxylan oligosaccharides and resistant starch on overnight glucose tolerance and markers of gut fermentation in healthy young adults.

PubMed

Boll, Elin V Johansson; Ekström, Linda M N K; Courtin, Christophe M; Delcour, Jan A; Nilsson, Anne C; Björck, Inger M E; Östman, Elin M

2016-06-01

Specific combinations of dietary fiber (DF) have been observed to result in improved glucose tolerance at a subsequent standardized breakfast. Arabinoxylan oligosaccharides (AXOS) are considered as DF with prebiotic potential, but so far no studies have investigated their metabolic effects in humans. This randomized cross-over study evaluated the overnight impact of breads containing AXOS-rich wheat bran extract and resistant starch (RS, Hi-Maize), separately or combined, on glucose tolerance, related metabolic parameters and markers of gut fermentation in healthy subjects. Evening reference and test products were: (1) reference white wheat flour bread (WWB), WWB supplemented with (2) AXOS and RS (WWB + AXOS + RS), (3) an increased content of either AXOS (WWB + hiAXOS) or (4) RS (WWB + hiRS). At the subsequent standardized breakfast, blood was sampled for 3 h to monitor glucose, insulin, nonesterified fatty acids, glucagon-like peptide (GLP)-1 and GLP-2. Breath hydrogen (H2) and short chain fatty acids (SCFA) were measured as markers of gut fermentation, and subjective appetite was rated using visual analog scales. Dose-dependent decreases in glucose responses were observed with increased AXOS over the duration of 3 h. Insulin sensitivity index was improved in the morning after the WWB + hiAXOS evening meal. An increase in breath H2 concentration and circulating SCFA was observed in the morning after both evening meals containing AXOS. The present study indicates that AXOS have the potential of improving glucose tolerance in an overnight perspective and suggested mechanisms are improved insulin sensitivity and increased gut fermentation.

Expression of m1-type muscarinic acetylcholine receptors by parvalbumin-immunoreactive neurons in the primary visual cortex: a comparative study of rat, guinea pig, ferret, macaque, and human.

PubMed

Disney, Anita A; Reynolds, John H

2014-04-01

Cholinergic neuromodulation is a candidate mechanism for aspects of arousal and attention in mammals. We have reported previously that cholinergic modulation in the primary visual cortex (V1) of the macaque monkey is strongly targeted toward GABAergic interneurons, and in particular that the vast majority of parvalbumin-immunoreactive (PV) neurons in macaque V1 express the m1-type (pirenzepine-sensitive, Gq-coupled) muscarinic ACh receptor (m1AChR). In contrast, previous physiological data indicates that PV neurons in rats rarely express pirenzepine-sensitive muscarinic AChRs. To examine further this apparent species difference in the cholinergic effectors for the primary visual cortex, we have conducted a comparative study of the expression of m1AChRs by PV neurons in V1 of rats, guinea pigs, ferrets, macaques, and humans. We visualize PV- and mAChR-immunoreactive somata by dual-immunofluorescence confocal microscopy and find that the species differences are profound; the vast majority (>75%) of PV-ir neurons in macaques, humans, and guinea pigs express m1AChRs. In contrast, in rats only ∼25% of the PV population is immunoreactive for m1AChRs. Our data reveal that while they do so much less frequently than in primates, PV neurons in rats do express Gq-coupled muscarinic AChRs, which appear to have gone undetected in the previous in vitro studies. Data such as these are critical in determining the species that represent adequate models for the capacity of the cholinergic system to modulate inhibition in the primate cortex. Copyright © 2013 Wiley Periodicals, Inc.

Reliability Sensitivity Analysis and Design Optimization of Composite Structures Based on Response Surface Methodology

NASA Technical Reports Server (NTRS)

Rais-Rohani, Masoud

2003-01-01

This report discusses the development and application of two alternative strategies in the form of global and sequential local response surface (RS) techniques for the solution of reliability-based optimization (RBO) problems. The problem of a thin-walled composite circular cylinder under axial buckling instability is used as a demonstrative example. In this case, the global technique uses a single second-order RS model to estimate the axial buckling load over the entire feasible design space (FDS) whereas the local technique uses multiple first-order RS models with each applied to a small subregion of FDS. Alternative methods for the calculation of unknown coefficients in each RS model are explored prior to the solution of the optimization problem. The example RBO problem is formulated as a function of 23 uncorrelated random variables that include material properties, thickness and orientation angle of each ply, cylinder diameter and length, as well as the applied load. The mean values of the 8 ply thicknesses are treated as independent design variables. While the coefficients of variation of all random variables are held fixed, the standard deviations of ply thicknesses can vary during the optimization process as a result of changes in the design variables. The structural reliability analysis is based on the first-order reliability method with reliability index treated as the design constraint. In addition to the probabilistic sensitivity analysis of reliability index, the results of the RBO problem are presented for different combinations of cylinder length and diameter and laminate ply patterns. The two strategies are found to produce similar results in terms of accuracy with the sequential local RS technique having a considerably better computational efficiency.

Close Positive Correlation between the Lymphocyte Response to Hen Egg White and House Dust Mites in Infants with Atopic Dermatitis.

PubMed

Kimura, Mitsuaki; Meguro, Takaaki; Ito, Yasunori; Tokunaga, Fumika; Hashiguchi, Akihiko; Seto, Shiro

2015-01-01

It was recently hypothesized that food allergens sensitize infants with atopic dermatitis (AD) via the skin. If this is the case, an intimate positive correlation should be observed between immune responses to both food and indoor allergens. One hundred and seven infants with AD and 32 controls were enrolled. The proliferation of lymphocytes stimulated with hen egg white (EW) or house dust mite (HDM) allergens was measured by means of an allergen-specific lymphocyte stimulation test (ALST). Cytokine production was measured in 13 patients and 4 controls. ALST responses for EW (EW-ALST) were significantly higher in AD infants than in control subjects (stimulation index: 7.98 vs. 2.54, p < 0.0001). HDM-ALST responses were also significantly higher in AD infants than in controls (stimulation index: 5.09 vs. 1.44, p < 0.0001). A significant positive correlation was seen between HDM-ALST and EW-ALST responses in AD infants aged 5-6 months (rs = 0.77, p < 0.000001). Serum levels of EW-specific IgE (EW-IgE) were significantly correlated with both EW-ALST (rs = 0.43, p < 0.05) and HDM-ALST levels (rs = 0.47, p < 0.05) in AD patients aged 3-4 months. Serum EW-IgE levels in AD infants were significantly correlated with the ratio of IL-4/IFN-γ production from lymphocytes stimulated with EW (rs = 0.62, p < 0.01) and with HDM (rs = 0.67, p < 0.005). This study describes the close positive correlation between EW- and HDM-specific immune responses in infants with AD. These results may support the hypothesis that both food and indoor allergens concurrently sensitize infants via the skin. © 2015 S. Karger AG, Basel.

Impact of a Common Genetic Variation Associated With Putamen Volume on Neural Mechanisms of Attention-Deficit/Hyperactivity Disorder.

PubMed

Xu, Bing; Jia, Tianye; Macare, Christine; Banaschewski, Tobias; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomáš; Poustka, Luise; Smolka, Michael N; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Desrivières, Sylvane

2017-05-01

In a recent genomewide association study of subcortical brain volumes, a common genetic variation at rs945270 was identified as having the strongest effect on putamen volume, a brain measurement linked to familial risk for attention-deficit/hyperactivity disorder (ADHD). To determine whether rs945270 might be a genetic determinant of ADHD, its effects on ADHD-related symptoms and neural mechanisms of ADHD, such as response inhibition and reward sensitivity, were explored. A large population sample of 1,834 14-year-old adolescents was used to test the effects of rs945270 on ADHD symptoms assessed through the Strengths and Difficulties Questionnaire and region-of-interest analyses of putamen activation by functional magnetic resonance imaging using the stop signal and monetary incentive delay tasks, assessing response inhibition and reward sensitivity, respectively. There was a significant link between rs945270 and ADHD symptom scores, with the C allele associated with lower symptom scores, most notably hyperactivity. In addition, there were sex-specific effects of this variant on the brain. In boys, the C allele was associated with lower putamen activity during successful response inhibition, a brain response that was not associated with ADHD symptoms. In girls, putamen activation during reward anticipation increased with the number of C alleles, most significantly in the right putamen. Remarkably, right putamen activation during reward anticipation tended to negatively correlate with ADHD symptoms. These results indicate that rs945270 might contribute to the genetic risk of ADHD partly through its effects on hyperactivity and reward processing in girls. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Hydroxy-Al and cell-surface negativity are responsible for the enhanced sensitivity of Rhodotorula taiwanensis to aluminum by increased medium pH.

PubMed

Zhao, Xue Qiang; Bao, Xue Min; Wang, Chao; Xiao, Zuo Yi; Hu, Zhen Min; Zheng, Chun Li; Shen, Ren Fang

2017-10-01

Aluminum (Al) is ubiquitous and toxic to microbes. High Al 3+ concentration and low pH are two key factors responsible for Al toxicity, but our present results contradict this idea. Here, an Al-tolerant yeast strain Rhodotorula taiwanensis RS1 was incubated in glucose media containing Al with a continuous pH gradient from pH 3.1-4.2. The cells became more sensitive to Al and accumulated more Al when pH increased. Calculations using an electrostatic model Speciation Gouy Chapman Stern indicated that, the increased Al sensitivity of cells was associated with AlOH 2+ and Al(OH) 2 + rather than Al 3+ . The alcian blue (a positively charged dye) adsorption and zeta potential determination of cell surface indicated that, higher pH than 3.1 increased the negative charge and Al adsorption at the cell surface. Taken together, the enhanced sensitivity of R. taiwanensis RS1 to Al from pH 3.1-4.2 was associated with increased hydroxy-Al and cell-surface negativity.

Genetic variants of FTO influence adiposity, insulin sensitivity, leptin levels, and resting metabolic rate in the Quebec Family Study.

PubMed

Do, Ron; Bailey, Swneke D; Desbiens, Katia; Belisle, Alexandre; Montpetit, Alexandre; Bouchard, Claude; Pérusse, Louis; Vohl, Marie-Claude; Engert, James C

2008-04-01

A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity. Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and expenditure. We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term study of extensively phenotyped individuals designed to investigate factors involved in adiposity. We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated with BMI (P = 0.0014), weight (P = 0.0059), and waist circumference (P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin (P = 0.011), homeostasis model assessment of insulin resistance (P = 0.038), and an insulin sensitivity index derived from an oral glucose tolerance test (P = 0.0091). Associations were also found with resting metabolic rate (RMR) (P = 0.042) and plasma leptin levels (P = 0.036). Adjustment for BMI abolished the associations with insulin sensitivity, RMR, and plasma leptin levels. These results confirm that genetic variation at the FTO locus contributes to the etiology of obesity, insulin resistance, and increased plasma leptin levels.

Variations in the four and a half LIM domains 1 gene (FHL1) are associated with fasting insulin and insulin sensitivity responses to regular exercise.

PubMed

Teran-Garcia, M; Rankinen, T; Rice, T; Leon, A S; Rao, D C; Skinner, J S; Bouchard, C

2007-09-01

The expression of the four and a half LIM domains 1 gene (FHL1) is increased in the muscle of individuals who show an improvement in insulin sensitivity index (S(I)) after 20 weeks of exercise training. The aim of the present study was to investigate associations between three FHL1 single nucleotide polymorphisms (SNPs) and variables derived from an IVGTT, both in the sedentary state and in response to exercise training, in participants in the HERITAGE Family Study. SNPs were typed using fluorescence polarisation methodology. Analyses were performed separately by sex and in black and white individuals. In black participants, no associations were found with any of the SNPs. In white women (n = 207), SNP rs9018 was associated with the disposition index (D(I)), which is calculated as S(I) generated from the MINMOD program (x10(-4) min(-1)[microU/ml](-1)) multiplied by acute insulin response to glucose (AIR(g); pmol/l x 10 min), and the glucose disappearance index (K(g)) training responses (p = 0.016 and p = 0.008, respectively). In white men (n = 222), all SNPs were associated with fasting glucose levels (p < or = 0.05) and SNP rs2180062 with the insulin sensitivity index (S(I)) (p = 0.04) in the sedentary state. Two SNPs were associated with fasting insulin training response. Fasting insulin decreased to a greater extent in carriers of the rs2180062 C allele (p = 0.01) and rs9018 T allele (p = 0.04). With exercise training, S(I) (x10(-4) min(-1)[microU/ml](-1): 0.68 +/- 0.20 vs -0.77 +/- 0.44, p = 0.046), D(I) (319 +/- 123 vs -528 +/- 260, p = 0.006) and K(g) (per 100 min: 0.09 +/- 0.04 vs -0.14 +/- 0.8, p = 0.03) improved more in the C allele carriers at rs2180062 than in the T allele carriers. Fasting insulin and S(I) responses to exercise training were associated with DNA sequence variation in FHL1 in white men. Whether these associations exist only in white men remains to be investigated.

Why don't you like me? Midfrontal theta power in response to unexpected peer rejection feedback.

PubMed

van der Molen, M J W; Dekkers, L M S; Westenberg, P M; van der Veen, F M; van der Molen, M W

2017-02-01

Social connectedness theory posits that the brain processes social rejection as a threat to survival. Recent electrophysiological evidence suggests that midfrontal theta (4-8Hz) oscillations in the EEG provide a window on the processing of social rejection. Here we examined midfrontal theta dynamics (power and inter-trial phase synchrony) during the processing of social evaluative feedback. We employed the Social Judgment paradigm in which 56 undergraduate women (mean age=19.67 years) were asked to communicate their expectancies about being liked vs. disliked by unknown peers. Expectancies were followed by feedback indicating social acceptance vs. rejection. Results revealed a significant increase in EEG theta power to unexpected social rejection feedback. This EEG theta response could be source-localized to brain regions typically reported during activation of the saliency network (i.e., dorsal anterior cingulate cortex, insula, inferior frontal gyrus, frontal pole, and the supplementary motor area). Theta phase dynamics mimicked the behavior of the time-domain averaged feedback-related negativity (FRN) by showing stronger phase synchrony for feedback that was unexpected vs. expected. Theta phase, however, differed from the FRN by also displaying stronger phase synchrony in response to rejection vs. acceptance feedback. Together, this study highlights distinct roles for midfrontal theta power and phase synchrony in response to social evaluative feedback. Our findings contribute to the literature by showing that midfrontal theta oscillatory power is sensitive to social rejection but only when peer rejection is unexpected, and this theta response is governed by a widely distributed neural network implicated in saliency detection and conflict monitoring. Copyright © 2016 Elsevier Inc. All rights reserved.

Life stories of young women who experience rejection from their mothers.

PubMed

Mosman, Selina C; Poggenpoel, Marie; Myburgh, Chris

2015-08-12

When a daughter perceives rejection from her mother, she is bound to be sensitive to rejection for most if not all of her life. Such an experience influences almost all future relationships. The purpose of this research was to explore and describe the life stories of young women who perceived rejection from their mothers and to formulate guidelines to assist them. A phenomenological interpretive method that is explorative, descriptive, and contextual was used to explore everyday life experiences. Network sampling was used. In-depth phenomenological interviews were conducted with the young women so that they could define the most important dimensions of their life stories and elaborate on what is relevant to them. They were asked: 'Tell me your life story.' One of the authors also had a life story of perceived maternal rejection; hence an auto-ethnography was critical and was included in the study. Thematic data analysis was applied. Themes that emerged from the data were that the young women: (1) perceive ongoing challenges in forming and sustaining relationships in their lives; (2) experience their lives as conflicted because their relationship with the central core of their existence, their mother, is perceived as tumultuous; and (3) experience fundamental links to be missing in their 'mother-daughter relationship'. Only a few women were interviewed regarding perceived rejection from their mothers. Further research in this regard is imperative.

Gender, body mass index, and PPARγ polymorphism are good indicators in hyperuricemia prediction for Han Chinese.

PubMed

Lee, Ming-Fen; Liou, Tsan-Hon; Wang, Weu; Pan, Wen-Harn; Lee, Wei-Jei; Hsu, Chung-Tan; Wu, Suh-Fen; Chen, Hsin-Hung

2013-01-01

Hyperuricemia is closely associated with obesity and metabolic abnormalities, which is also an independent risk factor for cardiovascular diseases. The PPARγ gene, which is linked to obesity and metabolic abnormalities in Han Chinese, might be considered a top candidate gene that is involved in hyperuricemia. This study recruited 457 participants, aged 20-40 years old, to investigate the associations of the PPARγ gene and metabolic parameters with hyperuricemia. Three tag-single nucleotide polymorphisms, rs2292101, rs4684846, and rs1822825, of the PPARγ gene were selected to explore their association with hyperuricemia. Risk genotypes on rs1822825 of the PPARγ gene exhibited statistical significance with hyperuricemia (odds ratio: 1.9; 95% confidence interval: 1.05-3.57). Although gender, body mass index (BMI), serum total cholesterol concentration, or protein intake per day were statistically associated with hyperuricemia, the combination of BMI, gender, and rs1822825, rather than that of age, serum lipid profile, blood pressure, and protein intake per day, satisfied the predictability for hyperuricemia (sensitivity: 69.3%; specificity: 83.7%) in Taiwan-born obese Han Chinese. BMI, gender, and the rs1822825 polymorphism in the PPARγ gene appeared good biomarkers in hyperuricemia; therefore, these powerful indicators may be included in the prediction of hyperuricemia to increase the accuracy of the analysis.

How does Pseudomonas fluorescens avoid suicide from its antibiotic pseudomonic acid?: Evidence for two evolutionarily distinct isoleucyl-tRNA synthetases conferring self-defense.

PubMed

Yanagisawa, Tatsuo; Kawakami, Makoto

2003-07-11

Two isoleucyl-tRNA synthetases (IleRSs) encoded by two distinct genes (ileS1 and ileS2) were identified in pseudomonic acid (mupirocin)-producing Pseudomonas fluorescens. The most striking difference between the two IleRSs (IleRS-R1 and IleRS-R2) is the difference in their abilities to resist pseudomonic acid. Purified IleRS-R2 showed no sensitivity to pseudomonic acid even at a concentration of 5 mm, 105 times higher than the Ki value of IleRS-R1. The amino acid sequence of IleRS-R2 exhibits eukaryotic features that are originally found in eukaryotic proteins. Escherichia coli cells transformed with the ileS2 gene exerted pseudomonic acid resistance more than did those transformed with ileS1. Cells transformed with both genes became almost as resistant as P. fluorescens. These results suggest that the presence of IleRS-R2 could be the major reason why P. fluorescens is intrinsically resistant to the antibiotic. Here we suggest that the evolutionary scenario of the eukaryotic ileS2 gene can be explained by gene acquisition and that the pseudomonic acid producer may have maintained the ileS2 gene to protect itself from pseudomonic acid.

Glycine and GABAA Ultra-Sensitive Ethanol Receptors as Novel Tools for Alcohol and Brain Research

PubMed Central

Naito, Anna; Muchhala, Karan H.; Asatryan, Liana; Trudell, James R.; Homanics, Gregg E.; Perkins, Daya I.; Alkana, Ronald L.

2014-01-01

A critical obstacle to developing effective medications to prevent and/or treat alcohol use disorders is the lack of specific knowledge regarding the plethora of molecular targets and mechanisms underlying alcohol (ethanol) action in the brain. To identify the role of individual receptor subunits in ethanol-induced behaviors, we developed a novel class of ultra-sensitive ethanol receptors (USERs) that allow activation of a single receptor subunit population sensitized to extremely low ethanol concentrations. USERs were created by mutating as few as four residues in the extracellular loop 2 region of glycine receptors (GlyRs) or γ-aminobutyric acid type A receptors (GABAARs), which are implicated in causing many behavioral effects linked to ethanol abuse. USERs, expressed in Xenopus oocytes and tested using two-electrode voltage clamp, demonstrated an increase in ethanol sensitivity of 100-fold over wild-type receptors by significantly decreasing the threshold and increasing the magnitude of ethanol response, without altering general receptor properties including sensitivity to the neurosteroid, allopregnanolone. These profound changes in ethanol sensitivity were observed across multiple subunits of GlyRs and GABAARs. Collectively, our studies set the stage for using USER technology in genetically engineered animals as a unique tool to increase understanding of the neurobiological basis of the behavioral effects of ethanol. PMID:25245406

Fatty acid translocase gene CD36 rs1527483 variant influences oral fat perception in Malaysian subjects.

PubMed

Ong, Hing-Huat; Tan, Yen-Nee; Say, Yee-How

2017-01-01

We determined whether single nucleotide polymorphisms (SNPs; rs1761667 and rs1527483) in the fatty acid translocase CD36 gene - a receptor for fatty acids - is associated with oral fat perception (OFP) of different fat contents in custards and commercially-available foods, and obesity measures in Malaysian subjects (n=313; 118 males, 293 ethnic Chinese; 20 ethnic Indians). A 170-mm visual analogue scale was used to assess the ratings of perceived fat content, oiliness and creaminess of 0%, 2%, 6% and 10% fat content-by-weight custards and low-fat/regular versions of commercially-available milk, mayonnaise and cream crackers. Overall, the subjects managed to significantly discriminate the fat content, oiliness and creaminess between low-fat/regular versions of milk and mayonnaise. Females rated the perception of fat content and oiliness of both milks higher, but ethnicity, obesity and adiposity status did not seem to play a role in influencing most of OFP. The overall minor allele frequencies for rs1761667 and rs1527483 were 0.30 and 0.26, respectively. Females and individuals with rs1527483 TT genotype significantly perceived greater creaminess of 10% fat-by-weight custard. Also, individuals with rs1527483 TT genotype and T allele significantly perceived greater fat content of cream crackers, independent of fat concentration. rs1761667 SNP did not significantly affect OFP, except for cream crackers. Both gene variants were also not associated with obesity measures. Taken together, this study supports the notion that CD36 - specifically rs1527483, plays a role in OFP, but not in influencing obesity in Malaysian subjects. Besides, gender is an important factor for OFP, where females had higher sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Gene Variants of TCF7L2 Influence Weight Loss and Body Composition During Lifestyle Intervention in a Population at Risk for Type 2 Diabetes

PubMed Central

Haupt, Axel; Thamer, Claus; Heni, Martin; Ketterer, Caroline; Machann, Jürgen; Schick, Fritz; Machicao, Fausto; Stefan, Norbert; Claussen, Claus D.; Häring, Hans-Ulrich; Fritsche, Andreas; Staiger, Harald

2010-01-01

OBJECTIVE The impact of the diabetes risk gene transcription factor 7-like 2 (TCF7L2) on body weight is unclear. As TCF7L2 is expressed in adipose tissue and involved in Wnt-dependent regulation of adipogenesis, we studied the impact of TCF7L2 variants on body composition and weight loss during lifestyle intervention. RESEARCH DESIGN AND METHODS We genotyped 309 German subjects at increased risk for type 2 diabetes for single nucleotide polymorphisms (SNPs) rs7903146, rs12255372, rs11196205, and rs7895340 in TCF7L2 and performed oral glucose tolerance tests before and after a 9-month lifestyle intervention. Fat distribution was quantified using whole-body magnetic resonance imaging/spectroscopy in a subgroup of 210 subjects. RESULTS After adjustment for confounding variables, we observed a negative impact of the type 2 diabetes allele of SNP rs7903146 on change in BMI (P = 0.0034) and on changes in nonvisceral (P = 0.0032) and visceral fat (P = 0.0165) during lifestyle intervention. An association of rs7903146 with lifestyle intervention-induced changes in insulin secretion, glucose concentrations, liver fat, or insulin sensitivity were not detected (all P > 0.2). Essentially the same results were obtained with SNP rs1255372. In contrast, we found no effects of SNPs rs11196205 and rs7895340 on change in BMI (all P ≥ 0.5). CONCLUSIONS Our data reveal that diabetes-associated alleles of TCF7L2 are associated with less weight loss in response to lifestyle intervention. Thus, diabetes-associated TCF7L2 gene variation predicts the success of lifestyle intervention in terms of weight loss and determines individual susceptibility toward environmental factors. PMID:20028944

Extending the Minority Stress Model to Incorporate HIV-Positive Gay and Bisexual Men's Experiences: a Longitudinal Examination of Mental Health and Sexual Risk Behavior.

PubMed

Rendina, H Jonathon; Gamarel, Kristi E; Pachankis, John E; Ventuneac, Ana; Grov, Christian; Parsons, Jeffrey T

2017-04-01

Minority stress theory represents the most plausible conceptual framework for explaining health disparities for gay and bisexual men (GBM). However, little focus has been given to including the unique stressors experienced by HIV-positive GBM. We explored the role of HIV-related stress within a minority stress model of mental health and condomless anal sex. Longitudinal data were collected on a diverse convenience sample of 138 highly sexually active, HIV-positive GBM in NYC regarding sexual minority (internalized homonegativity and gay-related rejection sensitivity) and HIV-related stressors (internalized HIV stigma and HIV-related rejection sensitivity), emotion dysregulation, mental health (symptoms of depression, anxiety, sexual compulsivity, and hypersexuality), and sexual behavior (condomless anal sex with all male partners and with serodiscordant male partners). Across both sexual minority and HIV-related stressors, internalized stigma was significantly associated with mental health and sexual behavior outcomes while rejection sensitivity was not. Moreover, path analyses revealed that emotion dysregulation mediated the influence of both forms of internalized stigma on symptoms of depression/anxiety and sexual compulsivity/hypersexuality as well as serodiscordant condomless anal sex. We identified two targets of behavioral interventions that may lead to improvements in mental health and reductions in sexual transmission risk behaviors-maladaptive cognitions underlying negative self-schemas and difficulties with emotion regulation. Techniques for cognitive restructuring and emotion regulation may be particularly useful in the development of interventions that are sensitive to the needs of this population while also highlighting the important role that structural interventions can have in preventing these disparities for future generations.

Extending the minority stress model to incorporate HIV-positive gay and bisexual men’s experiences: A longitudinal examination of mental health and sexual risk behavior

PubMed Central

Rendina, H. Jonathon; Gamarel, Kristi E.; Pachankis, John E.; Ventuneac, Ana; Grov, Christian; Parsons, Jeffrey T.

2016-01-01

Background Minority stress theory represents the most plausible conceptual framework for explaining health disparities for gay and bisexual men (GBM). However, little focus has been given to including the unique stressors experienced by HIV-positive GBM. Purpose We explored the role of HIV-related stress within a minority stress model of mental health and condomless anal sex. Methods Longitudinal data were collected on a diverse convenience sample of 138 highly sexually active, HIV-positive GBM in NYC regarding sexual minority (internalized homonegativity, gay-related rejection sensitivity) and HIV-related stressors (internalized HIV stigma, HIV-related rejection sensitivity), emotion dysregulation, mental health (symptoms of depression, anxiety, sexual compulsivity, and hypersexuality), and sexual behavior (condomless anal sex with all male partners and with serodiscordant male partners). Results Across both sexual minority and HIV-related stressors, internalized stigma was significantly associated with mental health and sexual behavior outcomes while rejection sensitivity was not. Moreover, path analyses revealed that emotion dysregulation mediated the influence of both forms of internalized stigma on symptoms of depression/anxiety and sexual compulsivity/hypersexuality as well as serodiscordant condomless anal sex. Conclusions We identified two targets of behavioral interventions that may lead to improvements in mental health and reductions in sexual transmission risk behaviors—maladaptive cognitions underlying negative self-schemas and difficulties with emotion regulation. Techniques for cognitive restructuring and emotion regulation may be particularly useful in the development of interventions that are sensitive to the needs of this population while also highlighting the important role that structural interventions can have in preventing these disparities for future generations. PMID:27502073

Negative incidental emotions augment fairness sensitivity

PubMed Central

Liu, Cuizhen; Chai, Jing Wen; Yu, Rongjun

2016-01-01

Previous studies have shown that task-unrelated emotions induced incidentally exert carryover effects on individuals’ subsequent decisions in financial negotiations. However, the specificity of these emotion effects are not clear. In three experiments, we systematically investigated the role of seven transiently induced basic emotions (disgust, sadness, anger, fear, happiness, surprise and neutral) on rejection of unfair offers using the ultimatum game. We found that all negative emotions (disgust, sadness, anger and fear), but not happiness or surprise, significantly increased rejection rates, suggesting that the effect of incidental negative emotions on fairness is not specific to the type of negative emotion. Our findings highlight the role of fleeting emotions in biasing decision-making processes and suggest that all incidental negative emotions exert similar effects on fairness sensitivity, possibly by potentiating attention towards negative aspects of the situation. PMID:27101931

Abnormal Social Reward Responses in Anorexia Nervosa: An fMRI Study.

PubMed

Via, Esther; Soriano-Mas, Carles; Sánchez, Isabel; Forcano, Laura; Harrison, Ben J; Davey, Christopher G; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Menchón, José M; Fernández-Aranda, Fernando; Cardoner, Narcís

2015-01-01

Patients with anorexia nervosa (AN) display impaired social interactions, implicated in the development and prognosis of the disorder. Importantly, social behavior is modulated by reward-based processes, and dysfunctional at-brain-level reward responses have been involved in AN neurobiological models. However, no prior evidence exists of whether these neural alterations would be equally present in social contexts. In this study, we conducted a cross-sectional social-judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive-subtype AN patients and 20 matched healthy controls. Brain activity during acceptance and rejection was investigated and correlated with severity measures (Eating Disorder Inventory -EDI-2) and with personality traits of interest known to modulate social behavior (The Sensitivity to Punishment and Sensitivity to Reward Questionnaire). Patients showed hypoactivation of the dorsomedial prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual areas during social rejection. Ventral striatum activation during rejection was positively correlated in patients with clinical severity scores. During acceptance, activation of the frontal opercula-anterior insula and dorsomedial/dorsolateral prefrontal cortices was differentially associated with reward sensitivity between groups. These results suggest an abnormal motivational drive for social stimuli, and involve overlapping social cognition and reward systems leading to a disruption of adaptive responses in the processing of social reward. The specific association of reward-related regions with clinical and psychometric measures suggests the putative involvement of reward structures in the maintenance of pathological behaviors in AN.

A Stress-Coping Model of Mental Illness Stigma: I. Predictors of Cognitive Stress Appraisal

PubMed Central

Rüsch, Nicolas; Corrigan, Patrick W.; Wassel, Abigail; Michaels, Patrick; Olschewski, Manfred; Wilkniss, Sandra; Batia, Karen

2009-01-01

Stigma can be a major stressor for individuals with schizophrenia and other mental illnesses. It is unclear, however, why some stigmatized individuals appraise stigma as more stressful, while others feel they can cope with the potential harm posed by public prejudice. We tested the hypothesis that the level of perceived public stigma and personal factors such as rejection sensitivity, perceived legitimacy of discrimination and ingroup perceptions (group value; group identification; entitativity, or the perception of the ingroup of people with mental illness as a coherent unit) predict the cognitive appraisal of stigma as a stressor. Stigma stress appraisal refers to perceived stigma-related harm exceeding perceived coping resources. Stress appraisal, stress predictors and social cue recognition were assessed in 85 people with schizophrenia, schizoaffective or affective disorders. Stress appraisal did not differ between diagnostic subgroups, but was positively correlated with rejection sensitivity. Higher levels of perceived societal stigma and holding the group of people with mental illness in low regard (low group value) independently predicted high stigma stress appraisal. These predictors remained significant after controlling for social cognitive deficits, depressive symptoms and diagnosis. Our findings support the model that public and personal factors predict stigma stress appraisal among people with mental illness, independent of diagnosis and clinical symptoms. Interventions that aim to reduce the impact of stigma on people with mental illness could focus on variables such as rejection sensitivity, a personal vulnerability factor, low group value and the cognitive appraisal of stigma as a stressor. PMID:19269140

A position-sensitive X-ray detector for the HEAO-A satellite.

NASA Technical Reports Server (NTRS)

Held, D.; Weisskopf, M. C.

1973-01-01

A position-sensitive, low-energy proportional counter system is described which will be used on the High-Energy Astronomical Observatory, Mission A, spacecraft. The associated system incorporates the capability to employ pulse-shape discrimination for background rejection and interpolation circuitry to locate the centroid of an X-ray event with an accuracy of approximately one eighth the cathode-wire spacing.

Combined measurement of directional Raman scattering and surface-plasmon-polariton cone from adsorbates on smooth planar gold surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nyamekye, Charles K. A.; Weibel, Stephen C.; Bobbitt, Jonathan M.

Directional-surface-plasmon-coupled Raman scattering (directional RS) has the combined benefits of surface plasmon resonance and Raman spectroscopy, and provides the ability to measure adsorption and monolayer-sensitive chemical information. Directional RS is performed by optically coupling a 50-nm gold film to a Weierstrass prism in the Kretschmann configuration and scanning the angle of the incident laser under total internal reflection. The collected parameters on the prism side of the interface include a full surface-plasmon-polariton cone and the full Raman signal radiating from the cone as a function of incident angle. An instrument for performing directional RS and a quantitative study of themore » instrumental parameters are herein reported. To test the sensitivity and quantify the instrument parameters, self-assembled monolayers and 10 to 100-nm polymer films are studied. The signals are found to be well-modeled by two calculated angle-dependent parameters: three-dimensional finite-difference time-domain calculations of the electric field generated in the sample layer and projected to the far-field, and Fresnel calculations of the reflected light intensity. This is the first report of the quantitative study of the full surface-plasmon-polariton cone intensity, cone diameter, and directional Raman signal as a function of incident angle. We propose that directional RS is a viable alternative to surface plasmon resonance when added chemical information is beneficial.« less

Functional brain abnormalities in major depressive disorder using the Hilbert-Huang transform.

PubMed

Yu, Haibin; Li, Feng; Wu, Tong; Li, Rui; Yao, Li; Wang, Chuanyue; Wu, Xia

2018-02-09

Major depressive disorder is a common disease worldwide, which is characterized by significant and persistent depression. Non-invasive accessory diagnosis of depression can be performed by resting-state functional magnetic resonance imaging (rs-fMRI). However, the fMRI signal may not satisfy linearity and stationarity. The Hilbert-Huang transform (HHT) is an adaptive time-frequency localization analysis method suitable for nonlinear and non-stationary signals. The objective of this study was to apply the HHT to rs-fMRI to find the abnormal brain areas of patients with depression. A total of 35 patients with depression and 37 healthy controls were subjected to rs-fMRI. The HHT was performed to extract the Hilbert-weighted mean frequency of the rs-fMRI signals, and multivariate receiver operating characteristic analysis was applied to find the abnormal brain regions with high sensitivity and specificity. We observed differences in Hilbert-weighted mean frequency between the patients and healthy controls mainly in the right hippocampus, right parahippocampal gyrus, left amygdala, and left and right caudate nucleus. Subsequently, the above-mentioned regions were included in the results obtained from the compared region homogeneity and the fractional amplitude of low frequency fluctuation method. We found brain regions with differences in the Hilbert-weighted mean frequency, and examined their sensitivity and specificity, which suggested a potential neuroimaging biomarker to distinguish between patients with depression and healthy controls. We further clarified the pathophysiological abnormality of these regions for the population with major depressive disorder.

Combined measurement of directional Raman scattering and surface-plasmon-polariton cone from adsorbates on smooth planar gold surfaces

DOE PAGES

Nyamekye, Charles K. A.; Weibel, Stephen C.; Bobbitt, Jonathan M.; ...

2017-09-15

Directional-surface-plasmon-coupled Raman scattering (directional RS) has the combined benefits of surface plasmon resonance and Raman spectroscopy, and provides the ability to measure adsorption and monolayer-sensitive chemical information. Directional RS is performed by optically coupling a 50-nm gold film to a Weierstrass prism in the Kretschmann configuration and scanning the angle of the incident laser under total internal reflection. The collected parameters on the prism side of the interface include a full surface-plasmon-polariton cone and the full Raman signal radiating from the cone as a function of incident angle. An instrument for performing directional RS and a quantitative study of themore » instrumental parameters are herein reported. To test the sensitivity and quantify the instrument parameters, self-assembled monolayers and 10 to 100-nm polymer films are studied. The signals are found to be well-modeled by two calculated angle-dependent parameters: three-dimensional finite-difference time-domain calculations of the electric field generated in the sample layer and projected to the far-field, and Fresnel calculations of the reflected light intensity. This is the first report of the quantitative study of the full surface-plasmon-polariton cone intensity, cone diameter, and directional Raman signal as a function of incident angle. We propose that directional RS is a viable alternative to surface plasmon resonance when added chemical information is beneficial.« less

A Test of the Homogeneous versus Heterogeneous Categories of the Repression-Sensitization Dimension

ERIC Educational Resources Information Center

Millimet, C. Raymond; Cohen, Howard J.

1973-01-01

A study was designed to examine further the psychometric relationships between the Marlowe-Crown Social Desirability Scale (MC-SDS) and a Repression-Sensitization (R-S) scale in order to affirm or deny the meaningfulness of pairing these two personality measures. The relationships between these measures was considered to be of sufficiently high…

Method variation in the impact of missing data on response shift detection.

PubMed

Schwartz, Carolyn E; Sajobi, Tolulope T; Verdam, Mathilde G E; Sebille, Veronique; Lix, Lisa M; Guilleux, Alice; Sprangers, Mirjam A G

2015-03-01

Missing data due to attrition or item non-response can result in biased estimates and loss of power in longitudinal quality-of-life (QOL) research. The impact of missing data on response shift (RS) detection is relatively unknown. This overview article synthesizes the findings of three methods tested in this special section regarding the impact of missing data patterns on RS detection in incomplete longitudinal data. The RS detection methods investigated include: (1) Relative importance analysis to detect reprioritization RS in stroke caregivers; (2) Oort's structural equation modeling (SEM) to detect recalibration, reprioritization, and reconceptualization RS in cancer patients; and (3) Rasch-based item-response theory-based (IRT) models as compared to SEM models to detect recalibration and reprioritization RS in hospitalized chronic disease patients. Each method dealt with missing data differently, either with imputation (1), attrition-based multi-group analysis (2), or probabilistic analysis that is robust to missingness due to the specific objectivity property (3). Relative importance analyses were sensitive to the type and amount of missing data and imputation method, with multiple imputation showing the largest RS effects. The attrition-based multi-group SEM revealed differential effects of both the changes in health-related QOL and the occurrence of response shift by attrition stratum, and enabled a more complete interpretation of findings. The IRT RS algorithm found evidence of small recalibration and reprioritization effects in General Health, whereas SEM mostly evidenced small recalibration effects. These differences may be due to differences between the two methods in handling of missing data. Missing data imputation techniques result in different conclusions about the presence of reprioritization RS using the relative importance method, while the attrition-based SEM approach highlighted different recalibration and reprioritization RS effects by attrition group. The IRT analyses detected more recalibration and reprioritization RS effects than SEM, presumably due to IRT's robustness to missing data. Future research should apply simulation techniques in order to make conclusive statements about the impacts of missing data according to the type and amount of RS.

The Gustin (CA6) Gene Polymorphism, rs2274333 (A/G), as a Mechanistic Link between PROP Tasting and Fungiform Taste Papilla Density and Maintenance

PubMed Central

Melis, Melania; Atzori, Elena; Cabras, Stefano; Zonza, Andrea; Calò, Carla; Muroni, Patrizia; Nieddu, Mariella; Padiglia, Alessandra; Sogos, Valeria; Tepper, Beverly J.; Tomassini Barbarossa, Iole

2013-01-01

Taste sensitivity to PROP varies greatly among individuals and is associated with polymorphisms in the bitter receptor gene TAS2R38, and with differences in fungiform papilla density on the anterior tongue surface. Recently we showed that the PROP non-taster phenotype is strongly associated with the G variant of polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic factor, gustin. The aims of this study were 1) to investigate the role of gustin gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla density and morphology, and 2) to investigate the effect of this gustin gene polymorphism on cell proliferation and metabolic activity. Sixty-four subjects were genotyped for both genes by PCR techniques, their PROP sensitivity was assessed by scaling and threshold methods, and their fungiform papilla density, diameter and morphology were determined. In vitro experiments examined cell proliferation and metabolic activity, following treatment with saliva of individuals with and without the gustin gene mutation, and with isolated protein, in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but papilla morphology was a function of gustin alone (p<0.0012). Treatment of isolated cells with saliva from individuals with the AA form of gustin or direct application of the active iso-form of gustin protein increased cell proliferation and metabolic activity (p<0.0135). These novel findings suggest that the rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on fungiform papilla development and maintenance, and could provide the first mechanistic explanation for why PROP super-tasters are more responsive to a broad range of oral stimuli. PMID:24040192

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

PubMed Central

Ursini, Gianluca; Cavalleri, Tommaso; Fazio, Leonardo; Angrisano, Tiziana; Iacovelli, Luisa; Porcelli, Annamaria; Maddalena, Giancarlo; Punzi, Giovanna; Mancini, Marina; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Calabrese, Francesca; Rampino, Antonio; Taurisano, Paolo; Giorgio, Annabella Di; Keller, Simona; Tarantini, Letizia; Sinibaldi, Lorenzo; Quarto, Tiziana; Popolizio, Teresa; Caforio, Grazia; Blasi, Giuseppe; Riva, Marco A.; De Blasi, Antonio; Chiariotti, Lorenzo; Bollati, Valentina; Bertolino, Alessandro

2016-01-01

Abstract Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val66Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes. PMID:26889735

Reasons for Smoking Among Tri-Ethnic Daily and Nondaily Smokers

PubMed Central

Scheuermann, Taneisha S.; Emami, Ashley S.; Basora, Brittany; Luo, Xianghua; Khariwala, Samir S.; Ahluwalia, Jasjit S.

2014-01-01

Introduction: Nondaily smokers experience adverse effects from tobacco use, yet they have been understudied compared to daily smokers. Understanding how reasons for smoking (RS) differ by smoking level, gender, and race/ethnicity could inform tailored interventions. Methods: A cross-sectional survey was administered through an online panel survey service to 2,376 current smokers who were at least 25 years of age. The sample was stratified to obtain equal numbers of 3 racial/ethnic groups (African American [AA], Latino, and White) across smoking level (native nondaily, converted nondaily, daily light, and daily moderate/heavy). Results: A 7-factor structure of a 20-item Modified Reasons for Smoking Scale (MRSS) was confirmed (each subscale alpha > 0.80). Each factor of the MRSS varied by smoking level, with nondaily smokers endorsing all RS less frequently than daily smokers (p < .0001). The 4 smoker subgroups incrementally differed from one another (p < .05) with several exceptions between converted nondaily and daily light smokers. Males reported stronger RS on 5 out of 7 reasons (p < .05). Females had higher scores on tension reduction/relaxation (p < .0001). Latinos reported stronger RS than Whites and AAs on all reasons (p < .05) except for tension reduction/relaxation (p > .05). AAs and Whites were comparable on all RS (p > .05). Conclusions: The present study highlights considerable variability across smoking level, gender, and race/ethnicity in strength of RS. Addressing subgroup differences in RS may contribute to more sensitive and effective prevention and treatment efforts. PMID:25011469

The effect of water table fluctuation on soil respiration in a lower coastal plain forested wetland in the southeastern U.S.

NASA Astrophysics Data System (ADS)

Miao, Guofang; Noormets, Asko; Domec, Jean-Christophe; Trettin, Carl C.; McNulty, Steve G.; Sun, Ge; King, John S.

2013-12-01

and environmental pressures on wetland hydrology may trigger changes in carbon (C) cycling, potentially exposing vast amounts of soil C to rapid decomposition. We measured soil CO2 efflux (Rs) continuously from 2009 to 2010 in a lower coastal plain forested wetland in North Carolina, U.S., to characterize its main environmental drivers. To understand and quantify the spatial variation due to microtopography and associated differences in hydrology, measurements were conducted at three microsites along a microtopographic gradient. The seasonal hysteresis in Rs differed by microtopographic location and was caused by the transitions between flooded and nonflooded conditions. Because flooded Rs was small, we reported Rs dynamics mainly during nonflooded periods. A nested model, modified from conventional Q10 (temperature sensitivity) model with dynamic parameters, provided a significantly better simulation on the observed variation of Rs. The model performed better with daily data, indicating that soil temperature (Ts) and water table depth (WTD) were the primary drivers for seasonal variation. The diel variation of Rs was high and independent of Ts and WTD, which both had small diel variations, suggesting the likely association with plant activity. Overall, the site-average soil CO2 efflux was approximately 960-1103 g C m-2 yr-1 in 2010, of which 93% was released during nonflooded periods. Our study indicates that Rs is highly linked to hydroperiod and microtopography in forested wetlands and droughts in wetlands will accelerate soil C loss.

Serum matrix metalloproteinase 3 in detecting remitting seronegative symmetrical synovitis with pitting edema syndrome: A case report.

PubMed

Kenzaka, Tsuneaki; Goda, Ken

2018-05-16

We report a case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen -B7 antigen was positive. Moreover, matrix metalloproteinase 3 (MMP-3) was high. She was diagnosed with RS3PE syndrome, and treatment with prednisolone (15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3PE syndrome symptoms.

Serum matrix metalloproteinase 3 in detecting remitting seronegative symmetrical synovitis with pitting edema syndrome: A case report

PubMed Central

Kenzaka, Tsuneaki; Goda, Ken

2018-01-01

We report a case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome in a 71-year-old woman. She referred to our hospital with finger stiffness, edema of both hands and feet, pain of bilateral shoulder, wrist, metacarpophalangeal, proximal interphalangeal, and ankle joints. Rheumatoid factor was negative, human leukocyte antigen -B7 antigen was positive. Moreover, matrix metalloproteinase 3 (MMP-3) was high. She was diagnosed with RS3PE syndrome, and treatment with prednisolone (15 mg/d) was started. One week after prednisolone treatment initiation, CRP decreased to negative, and joint pain was almost completely resolved. However, hand stiffness persisted, and MMP-3 level was still high. Thus, prednisolone dose was increased to 20 mg/d, and the stiffness resolved. Twenty days after treatment initiation, MMP-3 was normalized. MMP-3 was more indicative of RS3PE syndrome symptoms than CRP. Thus, MMP-3 seems to be more sensitive to RS3PE syndrome symptoms. PMID:29774220

Religiosity, magical ideation, and paranormal beliefs in anxiety disorders and obsessive-compulsive disorder: a cross-sectional study.

PubMed

Agorastos, Agorastos; Metscher, Tanja; Huber, Christian G; Jelinek, Lena; Vitzthum, Francesca; Muhtz, Christoph; Kellner, Michael; Moritz, Steffen

2012-10-01

The relation between religiosity/spirituality (R/S), personal beliefs, and mental health has been extensively studied. However, concerning anxiety disorders (ADs), empirical evidence is scarce. This study investigated the differences in R/S and magical/paranormal ideation among obsessive-compulsive disorder patients (OCD; n = 49), patients with other ADs (n = 36), and healthy controls (HCs; n = 35). Our results suggest negative religious coping as being the only parameter showing significantly higher scores in OCD and AD participants in comparison with HCs. Negative religious coping reflects negative functional expressions of R/S in stressful situations. Logistic regression also suggested negative religious coping as the strongest predictor of group affiliation to the nonhealthy group. Further results show no significant differences between other R/S, magical, and paranormal ideation traits among groups. This study underlines an important role of negative religious coping in ADs yet does not clearly indicate a specific causality. Religious-sensitive treatment targeting cognitive aspects of negative religious coping are discussed.

The C allele of ATM rs11212617 does not associate with metformin response in the Diabetes Prevention Program.

PubMed

Florez, Jose C; Jablonski, Kathleen A; Taylor, Andrew; Mather, Kieren; Horton, Edward; White, Neil H; Barrett-Connor, Elizabeth; Knowler, William C; Shuldiner, Alan R; Pollin, Toni I

2012-09-01

The C allele at the rs11212617 polymorphism in the ataxia-telangiectasia-mutated (ATM) gene has been associated with greater clinical response to metformin in people with type 2 diabetes. We tested whether this variant modified the effect of metformin in the Diabetes Prevention Program (DPP), in which metformin reduced diabetes incidence by 31% in volunteers with impaired glucose tolerance. We genotyped rs11212617 in 2,994 DPP participants and analyzed its effects on diabetes incidence and related traits. Contrary to expectations, C carriers enjoyed no preventive advantage on metformin; their hazard ratio, compared with A carriers, was 1.17 ([95% CI 0.96-1.42], P = 0.13) under metformin. There were no significant differences by genotype in metformin's effects on insulin sensitivity, fasting glucose, glycated hemoglobin, or disposition index. The reported association of rs11212617 with metformin response was not confirmed for diabetes prevention or for effects on relevant physiologic parameters in the DPP.

Immune mechanisms in organ allograft rejection. V. Pivotal role of the cytotoxic-suppressor T cell subset in the rejection of heart grafts bearing isolated class I disparities in the inbred rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowry, R.P.; Forbes, R.D.; Blackburn, J.H.

1985-11-01

The cellular requirements for rejection of heart grafts bearing isolated major histocompatibility complex (MHC) subregion RT1A-encoded class I disparities was assessed by adoptive transfer. Sublethally irradiated (780 rads) (PVG X WF)F1 recipients of irradiated PVG-RT1r1 heart grafts were selectively reconstituted with spleen cells from syngeneic donors previously sensitized with two sequential PVG-RT1r1 skin grafts. PVG-RT1r1 heart grafts were rejected acutely in recipients reconstituted with 10 X 10(6) unfractionated immune spleen cells or inocula (5 X 10(6) cells) depleted of SIg+ cells, but additional depletion of cytotoxic T cells and their precursors resulted in marked prolongation of graft survival. Reducing themore » reconstituting inocula from 4 X 10(6) to 2.5 X 10(6) spleen cells prolonged graft survival to that observed in unreconstituted recipients. Additional studies were performed to define the immunologic basis for prolonged survival of PVG-RT1r1 heart grafts in homozygous PVG recipients. Although lymphoid cells of naive PVG failed to proliferate on coculture with irradiated PVG-RT1r1, bulk cultures yielding but weak and variable CTL generation, lymphoid cells from specifically sensitized PVG proliferated and generated greater cytotoxic T lymphocyte (CTL) activity under identical conditions, strongly suggesting, therefore, that prolonged heart graft survival in this strain combination is related to low CTL precursor frequency.« less

Association between genetic variants of the ADD1 and GNB3 genes and blood pressure response to the cold pressor test in a Chinese Han population: the GenSalt Study.

PubMed

Wang, Laiyuan; Chen, Shufeng; Zhao, Qi; Hixson, James E; Rao, Dabeeru C; Jaquish, Cashell E; Huang, Jianfeng; Lu, Xiangfeng; Chen, Jichun; Cao, Jie; Li, Jianxin; Li, Hongfan; He, Jiang; Liu, De-Pei; Gu, Dongfeng

2012-08-01

Genetic factors influence blood pressure (BP) response to the cold pressor test (CPT), which is a phenotype related to hypertension risk. We examined the association between variants of the α-adducin (ADD1) and guanine nucleotide binding protein (G protein) β-polypeptide 3 (GNB3) genes and BP response to the CPT. A total of 1998 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity completed the CPT. The area under the curve (AUC) above the baseline BP during the CPT was used to measure the BP response. Twelve single-nucleotide polymorphisms (SNPs) of the ADD1 and GNB3 genes were selected and genotyped. Both single-marker and haplotype association analyses were conducted using linear mixed models. The rs17833172 and rs3775067 SNPs of the ADD1 gene and the rs4963516 SNP of the GNB3 gene were significantly associated with the BP response to CPT, even after adjusting for multiple testing. For the ADD1 gene, the AA genotype of SNP rs17833172 was associated with lower systolic BP (SBP) reactivity (P<0.0001) and faster BP recovery (P=0.0003). The TT genotype of rs3775067 was associated with slower SBP recovery (P=0.004). For the GNB3 gene, the C allele of SNP rs4963516 was associated with faster diastolic BP recovery (P=0.002) and smaller overall AUC (P=0.003). Haplotype analysis indicated that the CCGC haplotype of ADD1 constructed by rs1263359, rs3775067, rs4961 and rs4963 was significantly associated with the BP response to CPT. These data suggest that genetic variants of the ADD1 and GNB3 genes may have important roles in BP response to the CPT. Future studies aimed at replicating these novel findings are warranted.

Polymorphisms of endotoxin pathway and endotoxin exposure: in vitro IgE synthesis and replication in a birth cohort.

PubMed

Sahiner, U M; Semic-Jusufagic, A; Curtin, J A; Birben, E; Belgrave, D; Sackesen, C; Simpson, A; Yavuz, T S; Akdis, C A; Custovic, A; Kalayci, O

2014-12-01

Genetic variants in endotoxin signaling pathway are important in modulating the effect of environmental endotoxin on asthma and atopic phenotypes. Our objective was to determine the single nucleotide polymorphisms (SNPs) in the endotoxin signaling pathway that may influence in vitro IgE synthesis and to investigate the relationship between these variants and endotoxin exposure in relation to the development of asthma and atopy in a birth cohort. Peripheral blood mononuclear cells from 45 children with asthma were stimulated with 2 and 200 ng/ml lipopolysaccharide in vitro and IgE was measured in the culture supernatants. Children were genotyped for 121 SNPs from 30 genes in the endotoxin signaling pathway. Variants with a dose-response IgE production in relation to lipopolysaccharide (LPS) were selected for replication in a population-based birth cohort, in which we investigated the interaction between these SNPs and endotoxin exposure in relation to airway hyper-responsiveness, wheeze, and atopic sensitization. Twenty-one SNPs in nine genes (CD14, TLR4, IRF3, TRAF-6, TIRAP, TRIF, IKK-1, ST-2, SOCS1) were found to modulate the effect of endotoxin on in vitro IgE synthesis, with six displaying high linkage disequilibrium. Of the remaining 15 SNPs, for seven we found significant relationships between genotype and endotoxin exposure in the genetic association study in relation to symptomatic airway hyper-responsiveness (CD14-rs2915863 and rs2569191, TRIF-rs4807000), current wheeze (ST-2-rs17639215, IKK-1-rs2230804, and TRIF-rs4807000), and atopy (CD14-rs2915863 and rs2569192, TRAF-6-rs5030411, and IKK-1-rs2230804). Variants in the endotoxin signaling pathway are important determinants of asthma and atopy. The genotype effect is a function of the environmental endotoxin exposure. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reactivation of epigenetically silenced miR-512 and miR-373 sensitizes lung cancer cells to cisplatin and restricts tumor growth

PubMed Central

Adi Harel, S; Bossel Ben-Moshe, N; Aylon, Y; Bublik, D R; Moskovits, N; Toperoff, G; Azaiza, D; Biagoni, F; Fuchs, G; Wilder, S; Hellman, A; Blandino, G; Domany, E; Oren, M

2015-01-01

MicroRNAs (miRs) regulate a variety of cellular processes, and their impaired expression is involved in cancer. Silencing of tumor-suppressive miRs in cancer can occur through epigenetic modifications, including DNA methylation and histone deacetylation. We performed comparative miR profiling on cultured lung cancer cells before and after treatment with 5′aza-deoxycytidine plus Trichostatin A to reverse DNA methylation and histone deacetylation, respectively. Several tens of miRs were strongly induced by such ‘epigenetic therapy'. Two representatives, miR-512-5p (miR-512) and miR-373, were selected for further analysis. Both miRs were secreted in exosomes. Re-expression of both miRs augmented cisplatin-induced apoptosis and inhibited cell migration; miR-512 also reduced cell proliferation. TEAD4 mRNA was confirmed as a direct target of miR-512; likewise, miR-373 was found to target RelA and PIK3CA mRNA directly. Our results imply that miR-512 and miR-373 exert cell-autonomous and non-autonomous tumor-suppressive effects in lung cancer cells, where their re-expression may benefit epigenetic cancer therapy. PMID:25591738

Adoptive immunotherapy against kidney targets in dog-leukocyte antigen-identical mixed hematopoietic canine chimeras.

PubMed

Junghanss, Christian; Takatu, Alessandra; Little, Marie-Terese; Maciej Zaucha, J; Zellmer, Eustacia; Yunusov, Murad; Sale, George; Georges, George E; Storb, Rainer

2003-02-15

Stable mixed-donor-host-hematopoietic chimerism can serve as a platform for adoptive immunotherapy. Infusions of donor lymphocytes (DLI) sensitized against hematopoietic cells converted mixed hematopoietic into full-donor chimerism in dog-leukocyte antigen (DLA)-identical littermates. Whether sensitization against tissue of solid organs leads to organ-specific immunity that can be transferred by DLI was unknown and was investigated in these experiments using the kidney as target. DLA-identical recipients with established stable mixed-donor-host-hematopoietic chimerism were used. In five pairs, hematopoietic stem-cell transplant (HSCT) donors were sensitized by kidney transplantation from the respective chimeras. In a second group, five HSCT donors received vaccinations that were generated from kidney cells of the respective mixed chimeras. Twenty-eight days after sensitization, DLI were administered to the mixed-hematopoietic chimeras. All HSCT donors rejected their kidney grafts from their mixed-chimeric recipients within 22 to 45 days. DLI caused no sustained graft-versus-kidney effects in the mixed-chimeric recipients. However, DLI donors sensitized by kidney transplantation converted 4 of 5 mixed chimeras into virtually complete (>95%) donor-type chimeras, compared with 1 of 5 mixed chimeras given DLI by vaccination from sensitized donors. Although DLA-identical kidney grafts from mixed-hematopoietic chimeras were readily rejected by their HSCT donors, subsequent transfusions of sensitized-donor lymphocytes into mixed chimeras converted mixed to all-donor chimerism but failed to induce graft-versus-kidney effects. Vaccination strategies in lieu of kidney grafts failed to convert mixed chimerism.

Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation.

PubMed

Chruscinski, Andrzej; Huang, Flora Y Y; Nguyen, Albert; Lioe, Jocelyn; Tumiati, Laura C; Kozuszko, Stella; Tinckam, Kathryn J; Rao, Vivek; Dunn, Shannon E; Persinger, Michael A; Levy, Gary A; Ross, Heather J

2016-01-01

Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has increased sensitivity, and can detect autoantibodies in a multiplex fashion. Furthermore, our results suggest that this autoantibody array technology may help to identify patients at risk of rejection following heart transplantation and identify heart transplant recipients with AMR.

Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation

PubMed Central

Chruscinski, Andrzej; Huang, Flora Y. Y.; Nguyen, Albert; Lioe, Jocelyn; Tumiati, Laura C.; Kozuszko, Stella; Tinckam, Kathryn J.; Rao, Vivek; Dunn, Shannon E.; Persinger, Michael A.; Levy, Gary A.; Ross, Heather J.

2016-01-01

Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen). Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation) compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR) compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient sample, has increased sensitivity, and can detect autoantibodies in a multiplex fashion. Furthermore, our results suggest that this autoantibody array technology may help to identify patients at risk of rejection following heart transplantation and identify heart transplant recipients with AMR. PMID:26967734

Increased Loss Aversion in Unmedicated Patients with Obsessive-Compulsive Disorder.

PubMed

Sip, Kamila E; Gonzalez, Richard; Taylor, Stephan F; Stern, Emily R

2017-01-01

Obsessive-compulsive disorder (OCD) patients show abnormalities in decision-making and, clinically, appear to show heightened sensitivity to potential negative outcomes. Despite the importance of these cognitive processes in OCD, few studies have examined the disorder within an economic decision-making framework. Here, we investigated loss aversion, a key construct in the prospect theory that describes the tendency for individuals to be more sensitive to potential losses than gains when making decisions. Across two study sites, groups of unmedicated OCD patients ( n  = 14), medicated OCD patients ( n  = 29), and healthy controls ( n  = 34) accepted or rejected a series of 50/50 gambles containing varying loss/gain values. Loss aversion was calculated as the ratio of the likelihood of rejecting a gamble with increasing potential losses to the likelihood of accepting a gamble with increasing potential gains. Decision times to accept or reject were also examined and correlated with loss aversion. Unmedicated OCD patients exhibited significantly more loss aversion compared to medicated OCD or controls, an effect that was replicated across both sites and remained significant even after controlling for OCD symptom severity, trait anxiety, and sex. Post hoc analyses further indicated that unmedicated patients' increased likelihood to reject a gamble as its loss value increased could not be explained solely by greater risk aversion among patients. Unmedicated patients were also slower to accept than reject gambles, effects that were not found in the other two groups. Loss aversion was correlated with decision times in unmedicated patients but not in the other two groups. These data identify abnormalities of decision-making in a subgroup of OCD patients not taking psychotropic medication. The findings help elucidate the cognitive mechanisms of the disorder and suggest that future treatments could aim to target abnormalities of loss/gain processing during decision-making in this population.

Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.

PubMed

Knowles, Joshua W; Xie, Weijia; Zhang, Zhongyang; Chennamsetty, Indumathi; Chennemsetty, Indumathi; Assimes, Themistocles L; Paananen, Jussi; Hansson, Ola; Pankow, James; Goodarzi, Mark O; Carcamo-Orive, Ivan; Morris, Andrew P; Chen, Yii-Der I; Mäkinen, Ville-Petteri; Ganna, Andrea; Mahajan, Anubha; Guo, Xiuqing; Abbasi, Fahim; Greenawalt, Danielle M; Lum, Pek; Molony, Cliona; Lind, Lars; Lindgren, Cecilia; Raffel, Leslie J; Tsao, Philip S; Schadt, Eric E; Rotter, Jerome I; Sinaiko, Alan; Reaven, Gerald; Yang, Xia; Hsiung, Chao A; Groop, Leif; Cordell, Heather J; Laakso, Markku; Hao, Ke; Ingelsson, Erik; Frayling, Timothy M; Weedon, Michael N; Walker, Mark; Quertermous, Thomas

2015-04-01

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.

Interpersonal sensitivity and functioning impairment in youth at ultra-high risk for psychosis.

PubMed

Masillo, A; Valmaggia, L R; Saba, R; Brandizzi, M; Lindau, J F; Solfanelli, A; Curto, M; Narilli, F; Telesforo, L; Kotzalidis, G D; Di Pietro, D; D'Alema, M; Girardi, P; Fiori Nastro, P

2016-01-01

A personality trait that often elicits poor and uneasy interpersonal relationships is interpersonal sensitivity. The aim of the present study was to explore the relationship between interpersonal sensitivity and psychosocial functioning in individuals at ultra-high risk for psychosis as compared to help-seeking individuals who screened negative for an ultra-high risk of psychosis. A total sample of 147 adolescents and young adult who were help seeking for emerging mental health problems participated in the study. The sample was divided into two groups: 39 individuals who met criteria for an ultra-high-risk mental state (UHR), and 108 (NS). The whole sample completed the Interpersonal Sensitivity Measure (IPSM) and the Global Functioning: Social and Role Scale (GF:SS; GF:RS). Mediation analysis was used to explore whether attenuated negative symptoms mediated the relationship between interpersonal sensitivity and social functioning. Individuals with UHR state showed higher IPSM scores and lower GF:SS and GF:RS scores than NS participants. A statistically negative significant correlation between two IPSM subscales (Interpersonal Awareness and Timidity) and GF:SS was found in both groups. Our results also suggest that the relationship between the aforementioned aspects of interpersonal sensitivity and social functioning was not mediated by negative prodromal symptoms. This study suggests that some aspects of interpersonal sensitivity were associated with low level of social functioning. Assessing and treating interpersonal sensitivity may be a promising therapeutic target to improve social functioning in young help-seeking individuals.

Severing corneal nerves in one eye induces sympathetic loss of immune privilege and promotes rejection of future corneal allografts placed in either eye

PubMed Central

Paunicka, Kathryn J.; Mellon, Jessamee; Robertson, Danielle; Petroll, Matthew; Brown, Joseph R.; Niederkorn, Jerry Y.

2015-01-01

Less than 10% of corneal allografts undergo rejection even though HLA matching is not performed. However, second corneal transplants experience a three-fold increase in rejection, which is not due to prior sensitization to histocompatibility antigens shared by the first and second transplants since corneal grafts are selected at random without histocompatibility matching. Using a mouse model of penetrating keratoplasty we found that 50% of the initial corneal transplants survived, yet 100% of the subsequent corneal allografts (unrelated to the first graft) placed in the opposite eye underwent rejection. The severing of corneal nerves that occurs during surgery induced substance P (SP) secretion in both eyes, which disabled T regulatory cells that are required for allograft survival. Administration of an SP antagonist restored immune privilege and promoted graft survival. Thus, corneal surgery produces a sympathetic response that permanently abolishes immune privilege of subsequent corneal allografts, even those placed in the opposite eye and expressing a completely different array of foreign histocompatibility antigens from the first corneal graft. PMID:25872977

Can editors save peer review from peer reviewers?

PubMed

D'Andrea, Rafael; O'Dwyer, James P

2017-01-01

Peer review is the gold standard for scientific communication, but its ability to guarantee the quality of published research remains difficult to verify. Recent modeling studies suggest that peer review is sensitive to reviewer misbehavior, and it has been claimed that referees who sabotage work they perceive as competition may severely undermine the quality of publications. Here we examine which aspects of suboptimal reviewing practices most strongly impact quality, and test different mitigating strategies that editors may employ to counter them. We find that the biggest hazard to the quality of published literature is not selfish rejection of high-quality manuscripts but indifferent acceptance of low-quality ones. Bypassing or blacklisting bad reviewers and consulting additional reviewers to settle disagreements can reduce but not eliminate the impact. The other editorial strategies we tested do not significantly improve quality, but pairing manuscripts to reviewers unlikely to selfishly reject them and allowing revision of rejected manuscripts minimize rejection of above-average manuscripts. In its current form, peer review offers few incentives for impartial reviewing efforts. Editors can help, but structural changes are more likely to have a stronger impact.

Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

PubMed Central

McQuaid, Robyn J.; McInnis, Opal A.; Matheson, Kimberly; Anisman, Hymie

2016-01-01

Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243), conducted among white university students, examined the relation of trauma, depressive symptoms including suicidal ideation in relation to a single nucleotide polymorphism (SNP) within the oxytocin receptor gene (OXTR), rs53576, and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals with the polymorphism on both alleles (AA genotype) of the CD38 SNP had previously been linked to elevated plasma oxytocin levels. Consistent with the social sensitivity perspective, however, in the current study, individuals carrying the AA genotype displayed elevated feelings of alienation from parents and peers as well as increased levels of suicidal ideation. Moreover, they tended to report elevated depressive symptoms compared to CC homozygotes. It was also observed that the CD38 genotype moderated the relation between trauma and suicidal ideation scores, such that high levels of trauma were associated with elevated suicidal ideation among all CD38 genotypes, but this relationship was stronger among individuals with the AA genotype. In contrast, there was no relationship between the OXTR SNP, rs53576, depression or suicidal ideation. These findings support a social sensitivity hypothesis of oxytocin, wherein the AA genotype of the CD38 SNP, which has been considered the “protective allele” was associated with increased sensitivity and susceptibility to disturbed social relations and suicidal ideation. PMID:27486392

Isoflurane modulates excitability in the mouse thalamus via GABA-dependent and GABA-independent mechanisms

PubMed Central

Ying, Shui-Wang; Werner, David F.; Homanics, Gregg E.; Harrison, Neil L.; Goldstein, Peter A.

2009-01-01

Summary GABAergic neurons in the reticular thalamic nucleus (RTN) synapse onto thalamocortical neurons in the ventrobasal (VB) thalamus, and this reticulo-thalamocortical pathway is considered an anatomic target for general anesthetic-induced unconsciousness. A mutant mouse was engineered to harbor two amino acid substitutions (S270H, L277A) in the GABAA receptor (GABAA-R) α1 subunit; this mutation abolished sensitivity to the volatile anesthetic isoflurane in recombinant GABAA-Rs, and reduced in vivo sensitivity to isoflurane in the loss-of-righting-reflex assay. We examined the effects of the double mutation on GABAA-R-mediated synaptic currents and isoflurane sensitivity by recording from thalamic neurons in brain slices. The double mutation accelerated the decay, and decreased the ½ width of, evoked inhibitory postsynaptic currents (eIPSCs) in VB neurons and attenuated isoflurane-induced prolongation of the eIPSC. The hypnotic zolpidem, a selective modulator of GABAA-Rs containing the α1 subunit, prolonged eIPSC duration regardless of genotype, indicating that mutant mice incorporate α1-subunit containing GABAA-Rs into synapses. In RTN neurons, which lack the α1 subunit, eIPSC duration was longer than in VB, regardless of genotype. Isoflurane reduced the efficacy of GABAergic transmission from RTN to VB, independent of genotype, suggesting a presynaptic action in RTN neurons. Consistent with this observation, isoflurane inhibited both tonic action potential and rebound burst firing in the presence of GABAA-R blockade. The suppressed excitability in RTN neurons is likely mediated by isoflurane-enhanced Ba2+-sensitive, but 4-aminopyridine-insenstive, potassium conductances. We conclude that isoflurane enhances inhibition of thalamic neurons in VB via GABAA-R-dependent, but in RTN via GABAA-R-independent, mechanisms. PMID:18948126

PCB 136 Atropselectively Alters Morphometric and Functional Parameters of Neuronal Connectivity in Cultured Rat Hippocampal Neurons via Ryanodine Receptor-Dependent Mechanisms

PubMed Central

Yang, Dongren; Kania-Korwel, Izabela; Ghogha, Atefeh; Chen, Hao; Stamou, Marianna; Bose, Diptiman D.; Pessah, Isaac N.; Lehmler, Hans-Joachim; Lein, Pamela J.

2014-01-01

We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca2+-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (−)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (−)-PCB 136 is observed at concentrations ranging from 0.1 to 100nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca2+-sensitive dye demonstrates that (−)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca2+ oscillations. Similarly, (−)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure. PMID:24385416

Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition

PubMed Central

Kachel, Hamid S.; Patel, Rohit N.; Franzyk, Henrik; Mellor, Ian R.

2016-01-01

Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes. Whole-cell currents in response to application of acetylcholine alone or co-applied with PhTX analogue were studied by using two-electrode voltage-clamp. α3β4 nAChRs were most sensitive to PhTX-343 (IC50 = 12 nM at −80 mV) with α4β4, α4β2, α3β2, α7 and α1β1γδ being 5, 26, 114, 422 and 992 times less sensitive. In contrast α1β1γδ was most sensitive to PhTX-12 along with α3β4 (IC50 values of 100 nM) with α4β4, α4β2, α3β2 and α7 being 3, 3, 26 and 49 times less sensitive. PhTX-343 inhibition was strongly voltage-dependent for all subunit combinations except α7, whereas this was not the case for PhTX-12 for which weak voltage dependence was observed. We conclude that PhTX-343 mainly acts as an open-channel blocker of nAChRs with strong subtype selectivity. PMID:27901080

Rejection of atrial sensing artifacts by a pacing lead with short tip-to-ring spacing.

PubMed

Nash, A; Fröhlig, G; Taborsky, M; Stammwitz, E; Maru, F; Bouwens, L H M; Celiker, C

2005-01-01

The ability of a new pacing lead design, with a 10 mm tip-to-ring spacing, to facilitate rejection of sensed far field R-waves and myopotentials was evaluated. Measurements were performed in 66 patients. The occurrence of far field R-wave sensing and myopotential sensing was determined by means of the surface ECG and the ECG markers provided by the pacemaker. At an atrial sensitivity of 0.25 mV and an atrial blanking of 50 ms far field R-wave sensing was observed in 12 patients (18.2%) and at an atrial sensitivity of 1.0 mV no far-field R-wave sensing was observed. Myopotentials were sensed in 3 patients. In all patients the measured P-wave amplitude was at least twice the estimated amplitude of the far field R-wave at an atrial blanking of 50 ms. The results from this study show that a small tip-to-ring spacing allows for programming of a high atrial sensitivity and short atrial blanking with an acceptably low risk for atrial artifact sensing.

Dark matter search results from the PICO-2L C$$_3$$F$$_8$$ bubble chamber

DOE PAGES

Amole, C.

2015-06-11

New data are reported from the operation of a 2 liter C 3F 8 bubble chamber in the SNOLAB underground laboratory, with a total exposure of 211.5 kg days at four different energy thresholds below 10 keV. These data show that C 3F 8 provides excellent electron-recoil and alpha rejection capabilities at very low thresholds. The chamber exhibits an electron-recoil sensitivity of < 3.5 × 10 –10 and an alpha rejection factor of > 98.2%. These data also include the first observation of a dependence of acoustic signal on alpha energy. Twelve single nuclear recoil event candidates were observed duringmore » the run. The candidate events exhibit timing characteristics that are not consistent with the hypothesis of a uniform time distribution, and no evidence for a dark matter signal is claimed. Lastly, these data provide the most sensitive direct detection constraints on WIMP-proton spin-dependent scattering to date, with significant sensitivity at low WIMP masses for spin-independent WIMP-nucleon scattering.« less

Hollow-Fiber Spacesuit Water Membrane Evaporator

NASA Technical Reports Server (NTRS)

Bue, Grant; Trevino, Luis; Tsioulos, Gus; Mitchell, Keith; Settles, Joseph

2013-01-01

The hollow-fiber spacesuit water membrane evaporator (HoFi SWME) is being developed to perform the thermal control function for advanced spacesuits and spacecraft to take advantage of recent advances in micropore membrane technology in providing a robust, heat-rejection device that is less sensitive to contamination than is the sublimator. After recent contamination tests, a commercial-off-the-shelf (COTS) micro porous hollow-fiber membrane was selected for prototype development as the most suitable candidate among commercial hollow-fiber evaporator alternatives. An innovative design that grouped the fiber layers into stacks, which were separated by small spaces and packaged into a cylindrical shape, was developed into a full-scale prototype for the spacesuit application. Vacuum chamber testing has been performed to characterize heat rejection as a function of inlet water temperature and water vapor back-pressure, and to show contamination resistance to the constituents expected to be found in potable water produced by the wastewater reclamation distillation processes. Other tests showed tolerance to freezing and suitability to reject heat in a Mars pressure environment. In summary, HoFi SWME is a lightweight, compact evaporator for heat rejection in the spacesuit that is robust, contamination- insensitive, freeze-tolerant, and able to reject the required heat of spacewalks in microgravity, lunar, and Martian environments. The HoFi is packaged to reject 810 W of heat through 800 hours of use in a vacuum environment, and 370 W in a Mars environment. The device also eliminates free gas and dissolved gas from the coolant loop.

Isolated v-lesion represents a benign phenotype of vascular rejection of the kidney allograft- a retrospective study.

PubMed

Novotny, Marek; Hruba, Petra; Vichova, Petra; Maluskova, Jana; Honsova, Eva; Viklicky, Ondrej; Wohlfahrtova, Mariana

2018-05-31

While the detrimental impact of the humoral acute vascular rejection (AVR) phenotype is recognized, the prognostic significance of isolated v-lesion (IV) remains unclear. In this retrospective single-centre study, AVR was found in 98 out of 1015 patients (9.7%) who had undergone kidney transplantation in 2010-2014, with donor-specific antibodies (DSA) evaluated in all of them. The outcome of four AVR phenotypes was evaluated during median follow-up of 59 months; in 25 patients with IV, 18 with T cell-mediated vascular rejection (TCMRV), 19 with antibody-mediated vascular rejection (AMRV) and 36 with suspected antibody-mediated rejection (sAMRV). AVR was diagnosed mainly by for-cause biopsy (81%) early after transplantation (median 19 POD) and appeared as mild grade intimal arteritis. IV occurred in low sensitized patients after the first transplantation (96%) in the absence of DSA. IV responded satisfactorily to treatment (88%), showed no persistence of rejection in surveillance biopsy, had stable graft function, minimal proteinuria and excellent DCGS (96%). Contrary to that, Kaplan-Meier estimate of 3-year DCGS of AMRV was 66% (log rank=0.0004). Early IV represents a benign phenotype of AVR with a favourable outcome. This study prompts further research to evaluate the nature of IV before considering any change in the classification and management. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Appearance-based rejection sensitivity as a mediator of the relationship between symptoms of social anxiety and disordered eating cognitions and behaviors.

PubMed

Linardon, Jake; Braithwaite, Rachel; Cousins, Rachel; Brennan, Leah

2017-12-01

Previous research has established a robust relationship between symptoms of social anxiety and disordered eating. However, the mechanisms that may underpin this relationship are unclear. Appearance-based rejection sensitivity (ABRS)-the tendency to anxiously expect and overreact to signs of appearance-based rejection-may be a crucial explanatory mechanism, as ABRS has been shown to maintain social anxiety symptoms and predict disordered eating. We therefore tested whether ABRS mediated the relationship between social anxiety symptoms and various indices of disordered eating (over-evaluation of weight/shape, restraint, binge eating, compulsive exercise, and vomiting). Data from community-based females (n=299) and males (n=87) were analyzed. ABRS was shown to mediate the relationship between social anxiety and the over-evaluation, restraint, binge eating, and compulsive exercise frequency, but not vomiting. These effects also occurred for both females and males separately. Findings demonstrated that ABRS may be an important mechanism explaining why socially anxious individuals report elevated symptoms of disordered eating. Future research testing all proposed mediating variables of the social anxiety-disordered eating link in a single, integrative model is required to identify the most influential mechanisms driving this relationship. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chitosan coated carbon fiber microelectrode for selective in vivo detection of neurotransmitters in live zebrafish embryos

PubMed Central

Özel, Rıfat Emrah; Wallace, Kenneth N.; Andreescu, Silvana

2011-01-01

We report the development of a chitosan modified carbon fiber microelectrode for in vivo detection of serotonin. We find that chitosan has the ability to reject physiological levels of ascorbic acid interferences and facilitate selective and sensitive detection of in vivo levels of serotonin, a common catecholamine neurotransmitter. Presence of chitosan on the microelectrode surface was investigated using scanning electron microscopy (SEM) and cyclic voltammetry (CV). The electrode was characterized using differential pulse voltammetry (DPV). A detection limit of 1.6 nM serotonin with a sensitivity of 5.12 nA/µM, a linear range from 2 to 100 nM and a reproducibility of 6.5 % for n=6 electrodes were obtained. Chitosan modified microelectrodes selectively measure serotonin in presence of physiological levels of ascorbic acid. In vivo measurements were performed to measure concentration of serotonin in the live embryonic zebrafish intestine. The sensor quantifies in vivo intestinal levels of serotonin while successfully rejecting ascorbic acid interferences. We demonstrate that chitosan can be used as an effective coating to reject ascorbic acid interferences at carbon fiber microelectrodes, as an alternative to Nafion, and that chitosan modified microelectrodes are reliable tools for in vivo monitoring of changes in neurotransmitter levels. PMID:21601035

Genetic association of RIT2 rs12456492 polymorphism and Parkinson's disease susceptibility in Asian populations: a meta-analysis.

PubMed

Lu, Yanjun; Liu, Wei; Tan, Kun; Peng, Jing; Zhu, Yaowu; Wang, Xiong

2015-09-03

Recent studies investigating the association of the Ras-like without CAAX 2 (RIT2) polymorphism, rs12456492, with Parkinson's disease (PD) are controversial. We performed a meta-analysis to study the association between rs12456492 and PD susceptibility in Asian populations. Literature searches of PubMed and Embase were performed up to June 3, 2015, and the strength of the association between rs12456492 and PD was evaluated by odds ratios (OR) and 95% confidence intervals (CI). Four studies conducted between 2013 and 2015, comprising 2017 PD cases and 2010 controls, were included in the meta-analysis. Significant association of rs12456492 with PD was found in the dominant (GG + AG vs. AA: OR = 1.26, 95% CI = 1.20-1.44, P = 0.00) and additive models (GG vs. AA: OR = 1.38, 95% CI = 1.03-1.83, P = 0.030). Although sensitivity analysis found that the overall result was stable only in the dominant genetic model, a publication bias was also detected. Therefore, the results should be treated with caution. The current meta-analysis suggested that rs12456492 might be associated with increased PD risk in Asian populations, but studies using larger sample sizes and different ethnic populations will be needed to further confirm this association.

Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation, and child autistic traits: The moderating role of OXTR rs53576 genotype.

PubMed

Rijlaarsdam, Jolien; van IJzendoorn, Marinus H; Verhulst, Frank C; Jaddoe, Vincent W V; Felix, Janine F; Tiemeier, Henning; Bakermans-Kranenburg, Marian J

2017-03-01

Findings of studies investigating OXTR SNP rs53576 (G-A) variation in social behavior have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. Our goal was to examine OXTR rs53576 allele-specific sensitivity for neonatal OXTR DNA methylation in relation to (1) a prenatal maternal stress composite, and (2) child autistic traits. Prospective data from fetal life to age 6 years were collected in a total of 743 children participating in the Generation R Study. Prenatal maternal stress exposure was uniquely associated with child autistic traits but was unrelated to OXTR methylation across both OXTR rs53576 G-allele homozygous children and A-allele carriers. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction in the absence of main effects, suggesting that opposing effects cancelled each other out. Indeed, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G-allele homozygous children but not for A-allele carriers. These results highlight the importance of incorporating epi-allelic information and support the role of OXTR methylation in child autistic traits. Autism Res 2017, 10: 430-438. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Diurnal and seasonal change in stem respiration of Larix principis-rupprechtii trees, northern China.

PubMed

Yang, Yan; Zhao, Miao; Xu, Xiangtao; Sun, Zhenzhong; Yin, Guodong; Piao, Shilong

2014-01-01

Stem respiration is a critical and uncertain component of ecosystem carbon cycle. Few studies reported diurnal change in stem respiration as well as its linkage with climate. In this study, we investigated the diurnal and seasonal change in stem respiration and its linkage with environmental factors, in larch plantations of northern China from 2010 to 2012. The stem respiration per unit surface area (RS) showed clear diurnal cycles, ranging from 1.65±0.10 to 2.69±0.15 µmol m(-2) s(-1), increased after 6∶00, peaked at 15∶00 and then decreased. Both stem temperature and air temperature show similar diurnal pattern, while the diurnal pattern of air relative humidity is just the opposite to Rs. Similar to the diurnal cycles, seasonal change in RS followed the pattern of stem temperature. RS increased from May (1.28±0.07 µmol m(-2) s(-1)) when the stem temperature was relatively low and peaked in July (3.02±0.10 µmol m(-2) s(-1)) when the stem temperature was also the highest. Further regression analyses show that RS exponentially increases with increasing temperature, and the Q10 of Rs at mid daytime (1.97±0.17 at 12∶00 and 1.96±0.10 at 15∶00) is significantly lower than that of mid nighttime (2.60±0.14 at 00∶00 and 2.71±0.25 at 03∶00) Q10. This result not only implies that Rs is more sensitive to night than day warming, but also highlights that temperature responses of Rs estimated by only daytime measurement can lead to underestimated stem respiration increase under global warming, especially considering that temperature increase is faster during nighttime.

Genetic polymorphisms in pre-miRNAs predict the survival of non-small-cell lung cancer in Chinese population: a cohort study and a meta-analysis

PubMed Central

Xia, Lingzi; Yin, Zhihua; Li, Xuelian; Ren, Yangwu; Zhang, Haibo; Zhao, Yuxia; Zhou, Baosen

2017-01-01

Background To explore the association of genetic polymorphisms in pre-miRNA 30c-1 rs928508 and pre-miRNA 27a rs895819 with non-small-cell lung cancer prognosis. Materials and Methods 480 patients from five hospitals were enrolled in this prospective cohort study. They were followed up for five years. The association between genotypes and overall survival was assessed by Cox proportional hazards regression models. A meta-analysis was conducted to provide evidence for the effect of microRNA 27a rs895819 on cancer survival. Results G-allele containing genotypes of microRNA 30c-1 polymorphisms and C-allele containing genotypes of microRNA 27a were significantly associated with poorer overall survival. Multivariate Cox regression models indicated that these genetic polymorhpisms were independently predictive factors of poorer overall survival. In stratified analysis, the effect was observed in many strata. The significant joint effect was also observed in our study. Patients with G allele of microRNA 30c-1 rs928508 and C allele of microRNA 27a rs895819 had the poorer overall survival than patients with C allele of rs928508 and T allele of rs895819. The effect of the microRNA 27a rs895819 on non-small cell lung cancer overall survival was supported by the meta-analysis results. Conclusions The two single nucleotide polymorphisms in microRNA 30c-1 and microRNA 27a can predict the outcome of non-small cell lung cancer patients and they may decrease the sensitivity to anti-cancer drugs. PMID:29100439

Association between the oxytocin receptor (OXTR) gene and children's social cognition at 18 months.

PubMed

Wade, M; Hoffmann, T J; Wigg, K; Jenkins, J M

2014-09-01

At 18 months, children engage in a variety of social behaviors that reflect their nascent ability to understand the intentions of other people (e.g. joint attention, empathy, cooperation and self-recognition). Although numerous contextual factors have been shown to predict social cognition in young children, the genetic underpinnings of social-cognitive traits has been understudied in this age group. Owing to the known effects of oxytocin on adult social cognition and psychopathology, this study hypothesized that variability in the oxytocin receptor gene (OXTR) would be associated with social cognition in children at 18 months. Participants consisted of 350 children (182 males; 168 females) who were part of an ongoing longitudinal study that aimed to assess environmental and genetic contributions to children's cognitive and socio-emotional functioning. At 18 months, social cognition was measured using previously validated and developmentally sensitive tasks assessing children's joint attention, empathy, cooperation and self-recognition. Five potentially functional OXTR variants were genotyped: rs1042778, rs2254298, rs11131149, rs237897 and rs237899. A family-based association design was used to control for population admixture and stratification, and additional non-genomic covariates were controlled. Results showed that variability in rs11131149 was significantly associated with social cognition (P=0.009), with more copies of the major allele related to higher social cognition, and more copies of the minor (risk) allele associated with lower social cognition. A haplotype consisting of rs11131149-rs2254298 was also associated with social cognition (P=0.020). Implications for normative and pathological development are discussed, and key areas for future research are proposed. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Impact of elevated precipitation, nitrogen deposition and warming on soil respiration in a temperate desert

NASA Astrophysics Data System (ADS)

Yue, Ping; Cui, Xiaoqing; Gong, Yanming; Li, Kaihui; Goulding, Keith; Liu, Xuejun

2018-04-01

Soil respiration (Rs) is the most important source of carbon dioxide emissions from soil to atmosphere. However, it is unclear what the interactive response of Rs would be to environmental changes such as elevated precipitation, nitrogen (N) deposition and warming, especially in unique temperate desert ecosystems. To investigate this an in situ field experiment was conducted in the Gurbantunggut Desert, northwest China, from September 2014 to October 2016. The results showed that precipitation and N deposition significantly increased Rs, but warming decreased Rs, except in extreme precipitation events, which was mainly through its impact on the variation of soil moisture at 5 cm depth. In addition, the interactive response of Rs to combinations of the factors was much less than that of any single-factor, and the main response was a positive effect, except for the response from the interaction of increased precipitation and high N deposition (60 kg N ha-1 yr-1). Although Rs was found to show a unimodal change pattern with the variation of soil moisture, soil temperature and soil NH4+-N content, and it was significantly positively correlated to soil dissolved organic carbon (DOC) and pH, a structural equation model found that soil temperature was the most important controlling factor. Those results indicated that Rs was mainly interactively controlled by the soil multi-environmental factors and soil nutrients, and was very sensitive to elevated precipitation, N deposition and warming. However, the interactions of multiple factors largely reduced between-year variation of Rs more than any single-factor, suggesting that the carbon cycle in temperate deserts could be profoundly influenced by positive carbon-climate feedback.

Exploration of time-course combinations of outcome scales for use in a global test of stroke recovery.

PubMed

Goldie, Fraser C; Fulton, Rachael L; Dawson, Jesse; Bluhmki, Erich; Lees, Kennedy R

2014-08-01

Clinical trials for acute ischemic stroke treatment require large numbers of participants and are expensive to conduct. Methods that enhance statistical power are therefore desirable. We explored whether this can be achieved by a measure incorporating both early and late measures of outcome (e.g. seven-day NIH Stroke Scale combined with 90-day modified Rankin scale). We analyzed sensitivity to treatment effect, using proportional odds logistic regression for ordinal scales and generalized estimating equation method for global outcomes, with all analyses adjusted for baseline severity and age. We ran simulations to assess relations between sample size and power for ordinal scales and corresponding global outcomes. We used R version 2·12·1 (R Development Core Team. R Foundation for Statistical Computing, Vienna, Austria) for simulations and SAS 9·2 (SAS Institute Inc., Cary, NC, USA) for all other analyses. Each scale considered for combination was sensitive to treatment effect in isolation. The mRS90 and NIHSS90 had adjusted odds ratio of 1·56 and 1·62, respectively. Adjusted odds ratio for global outcomes of the combination of mRS90 with NIHSS7 and NIHSS90 with NIHSS7 were 1·69 and 1·73, respectively. The smallest sample sizes required to generate statistical power ≥80% for mRS90, NIHSS7, and global outcomes of mRS90 and NIHSS7 combined and NIHSS90 and NIHSS7 combined were 500, 490, 400, and 380, respectively. When data concerning both early and late outcomes are combined into a global measure, there is increased sensitivity to treatment effect compared with solitary ordinal scales. This delivers a 20% reduction in required sample size at 80% power. Combining early with late outcomes merits further consideration. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Evidence of Interaction Between PPARG2 and HNF4A Contributing to Variation in Insulin Sensitivity in Mexican Americans

PubMed Central

Black, Mary Helen; Fingerlin, Tasha E.; Allayee, Hooman; Zhang, Weiming; Xiang, Anny H.; Trigo, Enrique; Hartiala, Jaana; Lehtinen, Allison B.; Haffner, Steven M.; Bergman, Richard N.; McEachin, Richard C.; Kjos, Siri L.; Lawrence, Jean M.; Buchanan, Thomas A.; Watanabe, Richard M.

2015-01-01

OBJECTIVE We hypothesized that interaction between PPARG2 Pro12Ala and variants in the promoter region of HNF4A are associated with type 2 diabetes–related quantitative traits in Mexican-American families of a proband with previous gestational diabetes. RESEARCH DESIGN AND METHODS The BetaGene project genotyped PPARG2 Pro12Ala and nine HNF4A single nucleotide polymorphisms (SNPs) in 473 individuals in 89 families. Members of the proband generation had fasting glucose <126 mg/dl and were phenotyped by oral and intravenous glucose tolerance tests. RESULTS Neither PPARG2 Pro12Ala nor any of the nine HNF4A SNPs were independently associated with type 2 diabetes–related quantitative traits. However, the interaction between PPARG2 Pro12Ala and HNF4A rs2144908 was significantly associated with both insulin sensitivity (SI) (Bonferroni P = 0.0006) and 2-h insulin (Bonferroni P = 0.039). Subjects with at least one PPARG2 Ala allele and homozygous for the HNF4A rs2144908 A allele had 40% higher SI compared with individuals with at least one G allele. SI did not vary by rs2144908 genotype among PPARG2 Pro/Pro. The interaction result for SI was replicated by the Insulin Resistance Atherosclerosis Family Study (P = 0.018) in their San Antonio sample (n = 484) where subjects with at least one PPARG2 Ala allele and homozygous for the HNF4A rs2144908 A allele had a 29% higher SI compared with individuals with at least one G allele. However, the interaction was not replicated in their San Luis Valley sample (n = 496; P = 0.401). CONCLUSIONS Together, these results suggest that variation in PPARG2 and HNF4A may interact to regulate insulin sensitivity in Mexican Americans at risk for type 2 diabetes. PMID:18162503

Triglyceride to high-density lipoprotein cholesterol ratio predicts worse outcomes after acute ischaemic stroke.

PubMed

Deng, Q-W; Wang, H; Sun, C-Z; Xing, F-L; Zhang, H-Q; Zuo, L; Gu, Z-T; Yan, F-L

2017-02-01

The effect of the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) on clinical outcomes of acute ischaemic stroke (AIS) patients is unclear. This study sought to determine whether the TG/HDL-C ratio in AIS patients is associated with worse outcomes at 3 months. Acute ischaemic stroke patients who were admitted from 2011 to 2014 were enrolled in this study. TG, total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) were collected on admission. Three end-points were defined according to the modified Rankin scale (mRS) score at 3 months after symptom onset (excellent outcome, mRS 0-1; good outcome, mRS 0-2; and death, mRS 6). In all, 1006 patients were included (median age 68.5 years; 58.2% male). Higher TG, non-HDL-C and TG/HDL-C were strongly associated with the three end-points after adjustments: excellent [odds ratio (OR) = 1.39, OR 1.89 and OR 2.34, respectively] and good (OR 1.48, OR 2.90 and OR 4.12) outcomes, and death (OR 0.59, OR 0.29 and OR 0.26). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a TG/HDL-C ≥ 0.87 for excellent outcomes [area under the ROC curve (AUC) 0.596; sensitivity 73.3%; specificity 42.7%] and non-death (AUC 0.674; sensitivity 67.8%; specificity 60.6%) as well as a TG/HDL-C ≥ 1.01 for a good outcome (AUC 0.652; sensitivity 61.6%; specificity 63.2%). Patients with a TG/HDL-C < 0.87 had a 2.94-fold increased risk of death (95% confidence interval 1.89-4.55) compared with patients with a TG/HDL-C ≥ 0.87. A lower TG/HDL-C was independently associated with death and worse outcome at 3 months in AIS. © 2016 EAN.

Genome-wide interaction with the insulin secretion locus MTNR1B reveals CMIP as a novel type 2 diabetes susceptibility gene in African Americans.

PubMed

Keaton, Jacob M; Gao, Chuan; Guan, Meijian; Hellwege, Jacklyn N; Palmer, Nicholette D; Pankow, James S; Fornage, Myriam; Wilson, James G; Correa, Adolfo; Rasmussen-Torvik, Laura J; Rotter, Jerome I; Chen, Yii-Der I; Taylor, Kent D; Rich, Stephen S; Wagenknecht, Lynne E; Freedman, Barry I; Ng, Maggie C Y; Bowden, Donald W

2018-04-24

Although type 2 diabetes (T2D) results from metabolic defects in insulin secretion and insulin sensitivity, most of the genetic risk loci identified to date relates to insulin secretion. We reported that T2D loci influencing insulin sensitivity may be identified through interactions with insulin secretion loci, thereby leading to T2D. Here, we hypothesize that joint testing of variant main effects and interaction effects with an insulin secretion locus increases power to identify genetic interactions leading to T2D. We tested this hypothesis with an intronic MTNR1B SNP, rs10830963, which is associated with acute insulin response to glucose, a dynamic measure of insulin secretion. rs10830963 was tested for interaction and joint (main + interaction) effects with genome-wide data in African Americans (2,452 cases and 3,772 controls) from five cohorts. Genome-wide genotype data (Affymetrix Human Genome 6.0 array) was imputed to a 1000 Genomes Project reference panel. T2D risk was modeled using logistic regression with rs10830963 dosage, age, sex, and principal component as predictors. Joint effects were captured using the Kraft two degrees of freedom test. Genome-wide significant (P < 5 × 10 -8 ) interaction with MTNR1B and joint effects were detected for CMIP intronic SNP rs17197883 (P interaction  = 1.43 × 10 -8 ; P joint  = 4.70 × 10 -8 ). CMIP variants have been nominally associated with T2D, fasting glucose, and adiponectin in individuals of East Asian ancestry, with high-density lipoprotein, and with waist-to-hip ratio adjusted for body mass index in Europeans. These data support the hypothesis that additional genetic factors contributing to T2D risk, including insulin sensitivity loci, can be identified through interactions with insulin secretion loci. © 2018 WILEY PERIODICALS, INC.

Variability of soil CO2 efflux in a semi-arid grassland in Arizona

NASA Astrophysics Data System (ADS)

Krishnan, P.; Meyers, T. P.; Heuer, M.

2017-12-01

Soil surface CO2 efflux or soil respiration (RS) is one of the most important components of the global carbon cycle. So it is critical to evaluate the response of soil respiration to environmental conditions to predict how future climate and land cover changes influence the ecosystem carbon balance. Continuous half-hourly measurements of RS were made between the end of March to December 2015 in a semi-arid temperate grassland located on the Audubon Research Ranch in south western Arizona (31.5907N, 110.5104W, elevation 1496 m), USA. This first time measurements of Rs over this site using an automated soil chamber were used to investigate the seasonal and diurnal variation of Rs and its relationship to environmental variables. The mean annual air temperature and precipitation at this site were 16 deg C and 370 mm with more than 60% of the annual precipitation was received during the North American monsoon period (July-September). Following the onset of the monsoon, drastic changes in vegetation growth occured turning the ecosystem to a carbon sink by August. Temporal variability in Rs was closely related to the changes in near surface soil temperature at 2 cm (Ts) and soil water content at 5 cm (θ). Half -hourly Rs varied from nearly 0.1 μmol m-2 s-1 in the winter months to a maximum of 5 μmol m-2 s-1 in the peak growing season in August. During the dry pre-monsoon period (May -June), Rs was relatively low (<2 μmol m-2 s-1) even though soil temperature was the highest at the site. Rs significantly increased following rain events during the warm growing season reaching its peak in August. With the end of the growing season Rs continue to decrease following the temporal variation in Ts. Results show that there is a threshold of θ below which Rs were significantly reduced. For θ > 0.0.08 m3 m-3, RS was positively correlated to soil temperature at the 2 cm depth following an exponential relationship. Below this value of θ, RS was largely decoupled from TS dropping to less than half of their maximum values during wet soil conditions. Analysis of daily mean nighttime Rs for the year showed that for periods with θ below the threshold, the sensitivity of RS to temperature were substantially reduced resulting in a Q10 significantly < 2, thereby confirming that RS was less affected by soil temperature under low soil water conditions at this site.

Effects of Task Familiarity on Stress Responses of Repressors and Sensitizers

ERIC Educational Resources Information Center

Pagano, Don F.

1973-01-01

R.S. Lazarus's theory of coping was used to investigate appraisal and reappraisal of threat in repressors and sensitizers. Two indexes of stress, self-report ratings of affect and palmar skin conductance, were measured prior to performance on a reaction time task, after one-third of the task was completed and after two-thirds of the task was…

Role of resistant starch on diabetes risk factors in people with prediabetes: Design, conduct, and baseline results of the STARCH trial.

PubMed

Marlatt, Kara L; White, Ursula A; Beyl, Robbie A; Peterson, Courtney M; Martin, Corby K; Marco, Maria L; Keenan, Michael J; Martin, Roy J; Aryana, Kayanush J; Ravussin, Eric

2018-02-01

Dietary resistant starch (RS) might alter gastrointestinal tract function in a manner that improves human health, particularly among adults at risk for diabetes. Here, we report the design and baseline results (with emphasis on race differences) from the STARCH trial, the first comprehensive metabolic phenotyping of people with prediabetes enrolled in a randomized clinical trial testing the effect of RS on risk factors for diabetes. Overweight/obese participants (BMI≥27kg/m 2 and weight≤143kg), age 35-75y, with confirmed prediabetes were eligible. Participants were randomized to consume 45g/day of RS (RS=amylose) or amylopectin (Control) for 12weeks. The study was designed to evaluate the effect of RS on insulin sensitivity and secretion, ectopic fat, and inflammatory markers. Secondary outcomes included energy expenditure, substrate oxidation, appetite, food intake, colonic microbial composition, fecal and plasma levels of short-chain fatty acids, fecal RS excretion, and gut permeability. Out of 280 individuals screened, 68 were randomized, 65 started the intervention, and 63 were analyzed at baseline (mean age 55y, BMI 35.6kg/m 2 ); 2 were excluded from baseline analyses due to abnormal insulin and diabetes. Sex and race comparisons at baseline were reported. African-Americans had higher baseline acute insulin response to glucose (AIRg measured by frequently sampled intravenous glucose tolerance test) compared to Caucasians, despite having less visceral adipose tissue mass and intrahepatic lipid; all other glycemic variables were similar between races. Sleep energy expenditure was ~90-100kcal/day lower in African-Americans after adjusting for insulin sensitivity and secretion. This manuscript provides an overview of the strategy used to enroll people with prediabetes into the STARCH trial and describes methodologies used in the assessment of risk factors for diabetes. Clinicaltrials.gov identifier: STARCH (NCT01708694). The present study reference can be found here: https://clinicaltrials.gov/ct2/show/NCT01708694. Submission Category: "Study Design, Statistical Design, Study Protocols". Copyright © 2017. Published by Elsevier Inc.

Vulnerability-specific stress generation: Childhood emotional abuse and the mediating role of depressogenic interpersonal processes.

PubMed

Hernandez, Evelyn M; Trout, Zoë M; Liu, Richard T

2016-12-01

Stress generation in depression (i.e. the tendency for depression-prone individuals to experience more life stress that is in part influenced by the individual) has been well established. However, more research is necessary to clarify the role of specific types of life stress in this effect. The current study extends the stress generation hypothesis by examining whether the type of stress involved is contingent upon the nature of the individual's particular vulnerability. Childhood emotional abuse and interpersonal vulnerability factors were predicted to be associated with prospective interpersonal dependent but not non-interpersonal or independent stress. These interpersonal factors were examined as mediators of the association between childhood emotional abuse and interpersonal stress generation. Data were collected from 185 undergraduate participants at two time-points, four months apart. At baseline, participants completed assessments of depressive symptoms, childhood abuse history, interpersonal risk factors (rejection sensitivity, excessive reassurance-seeking, and negative feedback-seeking), and a diagnostic interview for depression. At the follow-up assessment, participants completed a life stress interview. Childhood emotional abuse prospectively predicted greater interpersonal dependent stress, but not non-interpersonal dependent or independent stress. Only rejection sensitivity mediated this relationship. Consistent with the stress generation hypothesis, neither childhood emotional abuse nor the three interpersonal risk factors predicted independent stress. These findings suggest that targeting interpersonal vulnerabilities in clinical settings, particularly rejection sensitivity, among individuals with a history of childhood emotional abuse, may help to reduce the occurrence of interpersonal dependent stress, thus possibly decreasing risk for depression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in reference evapotranspiration and its driving factors in the middle reaches of Yellow River Basin, China.

PubMed

She, Dunxian; Xia, Jun; Zhang, Yongyong

2017-12-31

Reference evapotranspiration (ET 0 ) is important for agricultural, environmental and other studies, and understanding the attribution of its change is helpful to provide information for irrigation scheduling and water resources management. The present study investigates the attribution of the change of ET 0 at 49 meteorological stations in the middle reaches of Yellow River basin (MRYRB) of China from 1960 to 2012. Results show that annual ET 0 increases from the northwest to the southeast of MRYRB in space. We find that annual ET 0 clearly presents a zigzag change pattern rather than a monotonically change during the whole period. The detected three breakpoints at 1972, 1988 and 1997 divide the whole period into four subperiods. The sensitivity analysis indicates that the ET 0 is the most sensitive to surface solar radiation (Rs), followed by relative humidity (RH) and mean air temperature (T), and the least sensitive to wind speed (u) in our study area. Furthermore, we find that ET 0 is becoming less sensitive to RH and more sensitive to T during 1960-2012. The attributions of the change in ET 0 vary largely at different regions and subperiods. The declined wind speed is the dominant factor, followed by Rs to the ET 0 reduction during 1960-2012. Further analysis shows that Rs and u are the two major contributing factors that control the change of ET 0 at most stations and during most subperiods. Our study confirms that the change of ET 0 is influenced by the complex interactions of climatic factors, and the dominant factor to the change of ET 0 is different in various regions and time periods. The results presented here can provide a reference for agricultural production and water resources management in MRYRB as well as other semi-arid and semi-humid regions. Copyright © 2017 Elsevier B.V. All rights reserved.

ACh-induced hyperpolarization and decreased resistance in mammalian type II vestibular hair cells.

PubMed

Poppi, Lauren A; Tabatabaee, Hessam; Drury, Hannah R; Jobling, Phillip; Callister, Robert J; Migliaccio, Americo A; Jordan, Paivi M; Holt, Joseph C; Rabbitt, Richard D; Lim, Rebecca; Brichta, Alan M

2018-01-01

In the mammalian vestibular periphery, electrical activation of the efferent vestibular system (EVS) has two effects on afferent activity: 1) it increases background afferent discharge and 2) decreases afferent sensitivity to rotational stimuli. Although the cellular mechanisms underlying these two contrasting afferent responses remain obscure, we postulated that the reduction in afferent sensitivity was attributed, in part, to the activation of α9- containing nicotinic acetylcholine (ACh) receptors (α9*nAChRs) and small-conductance potassium channels (SK) in vestibular type II hair cells, as demonstrated in the peripheral vestibular system of other vertebrates. To test this hypothesis, we examined the effects of the predominant EVS neurotransmitter ACh on vestibular type II hair cells from wild-type (wt) and α9-subunit nAChR knockout (α9 -/- ) mice. Immunostaining for choline acetyltransferase revealed there were no obvious gross morphological differences in the peripheral EVS innervation among any of these strains. ACh application onto wt type II hair cells, at resting potentials, produced a fast inward current followed by a slower outward current, resulting in membrane hyperpolarization and decreased membrane resistance. Hyperpolarization and decreased resistance were due to gating of SK channels. Consistent with activation of α9*nAChRs and SK channels, these ACh-sensitive currents were antagonized by the α9*nAChR blocker strychnine and SK blockers apamin and tamapin. Type II hair cells from α9 -/- mice, however, failed to respond to ACh at all. These results confirm the critical importance of α9nAChRs in efferent modulation of mammalian type II vestibular hair cells. Application of exogenous ACh reduces electrical impedance, thereby decreasing type II hair cell sensitivity. NEW & NOTEWORTHY Expression of α9 nicotinic subunit was crucial for fast cholinergic modulation of mammalian vestibular type II hair cells. These findings show a multifaceted efferent mechanism for altering hair cell membrane potential and decreasing membrane resistance that should reduce sensitivity to hair bundle displacements.

rs3212227 SNP in the IL12B Gene Prevents Delayed Graft Function after Kidney Transplantation.

PubMed

Perovic, Vladimir; Markovic, Milos; Kravljaca, Milica; Milosevic, Emina; Djoric, Milica; Pravica, Vera; Naumovic, Radomir

2018-05-10

Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients. Our study involved 152 kidney transplant recipients on standard immunosuppressive regimen which included calcineurin inhibitors, mycophenolic acid derivatives and corticosteroids. Genotyping of IFNG, TNFA, IL10 and IL12B was performed using commercial TaqMan assays. We found association between the carriers of AA genotype of IL12B +1188A/C polymorphism (rs3212227) and a lower rate of DGF (p = 0.037, OR = 0.45, 95% CI = 0.21-0.96), implying protective role of A allele in the pathogenesis of DGF in kidney transplant recipients, whereas no such association was observed with AR. None of the analyzed SNPs in TNFA (-308G/A), IFNG (+874T/A), IL10 (-1082G/A, -819T/C, -592C/A) were associated with AR or DGF in our patients. Our study shows a preliminary evidence that the AA genotype of rs3212227 SNP in the IL12B gene might be associated with a lower risk for DGF after kidney transplantation. In the future, additional well-designed large studies are required for the validation of our results. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process.

PubMed

Aalaei-Andabili, Seyed Hossein; Rezaei, Nima

2016-01-01

Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

The sensitivity of soil respiration to soil temperature, moisture, and carbon supply at the global scale.

PubMed

Hursh, Andrew; Ballantyne, Ashley; Cooper, Leila; Maneta, Marco; Kimball, John; Watts, Jennifer

2017-05-01

Soil respiration (Rs) is a major pathway by which fixed carbon in the biosphere is returned to the atmosphere, yet there are limits to our ability to predict respiration rates using environmental drivers at the global scale. While temperature, moisture, carbon supply, and other site characteristics are known to regulate soil respiration rates at plot scales within certain biomes, quantitative frameworks for evaluating the relative importance of these factors across different biomes and at the global scale require tests of the relationships between field estimates and global climatic data. This study evaluates the factors driving Rs at the global scale by linking global datasets of soil moisture, soil temperature, primary productivity, and soil carbon estimates with observations of annual Rs from the Global Soil Respiration Database (SRDB). We find that calibrating models with parabolic soil moisture functions can improve predictive power over similar models with asymptotic functions of mean annual precipitation. Soil temperature is comparable with previously reported air temperature observations used in predicting Rs and is the dominant driver of Rs in global models; however, within certain biomes soil moisture and soil carbon emerge as dominant predictors of Rs. We identify regions where typical temperature-driven responses are further mediated by soil moisture, precipitation, and carbon supply and regions in which environmental controls on high Rs values are difficult to ascertain due to limited field data. Because soil moisture integrates temperature and precipitation dynamics, it can more directly constrain the heterotrophic component of Rs, but global-scale models tend to smooth its spatial heterogeneity by aggregating factors that increase moisture variability within and across biomes. We compare statistical and mechanistic models that provide independent estimates of global Rs ranging from 83 to 108 Pg yr -1 , but also highlight regions of uncertainty where more observations are required or environmental controls are hard to constrain. © 2016 John Wiley & Sons Ltd.

Variation in PPARG is associated with longitudinal change in insulin resistance in Mexican Americans at risk for type 2 diabetes.

PubMed

Black, Mary Helen; Wu, Jun; Takayanagi, Miwa; Wang, Nan; Taylor, Kent D; Haritunians, Talin; Trigo, Enrique; Lawrence, Jean M; Watanabe, Richard M; Buchanan, Thomas A; Xiang, Anny H

2015-03-01

Peroxisome proliferator-activated receptor gamma (PPARG) is a susceptibility locus for type 2 diabetes mellitus (T2DM). Although cross-sectional associations have been reported, primarily for Pro12Ala, few longitudinal studies in nondiabetic populations have been conducted. This study aimed to examine whether and to what extent variation in PPARG is associated with longitudinal changes in anthropometric and metabolic traits in Mexican Americans at risk for T2DM. Subjects were participants of BetaGene, a family-based study of obesity, insulin resistance, and β-cell function, who completed a baseline and follow-up study visit (n = 378; mean followup, 4.6 ± 1.5 y). Phenotypes included body fat assessed by dual-energy x-ray absorptiometry; insulin sensitivity (SI), acute insulin response, and β-cell function (disposition index; DI) were estimated from iv glucose tolerance tests with Minimal Model analysis. Eighteen tag single nucleotide polymorphisms (SNPs) capturing variation in a 156-kb region surrounding PPARG were tested for association with changes in longitudinal traits. P-values were Bonferroni-corrected for multiple testing. Six SNPs (rs2972164, rs11128598, rs17793951, rs1151996, rs1175541, rs3856806) were significantly associated with rate of change in SI after adjustment for age, sex, and body fat percentage, but not with changes in adiposity. rs17793951 also had a significant effect on change in DI over time. Association between rs1175541 and change in SI varied by changes in adiposity such that only carriers of the minor allele who reduced body fat over followup improved SI. rs1306470 (captured Pro12Ala, r(2) = 0.9) was not associated with rates of change in any traits and its effects were not modified by changes in adiposity. Variation in PPARG, but not Pro12Ala, contributes to declining SI and concomitant deterioration in β-cell function in Mexican Americans at risk for T2DM.

Posttransplant soluble CD30 as a predictor of acute renal allograft rejection.

PubMed

Kamali, Koosha; Abbasi, Mohammad Amin; Farokhi, Babak; Abbasi, Ata; Fallah, Parvane; Seifee, Mohammad Hasan; Ghadimi, Naime; Rezaie, Alireza R

2009-12-01

Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P < .001), while sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 -/+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.

Diagnostic significance of rib series in minor thorax trauma compared to plain chest film and computed tomography.

PubMed

Hoffstetter, Patrick; Dornia, Christian; Schäfer, Stephan; Wagner, Merle; Dendl, Lena M; Stroszczynski, Christian; Schreyer, Andreas G

2014-01-01

Rib series (RS) are a special radiological technique to improve the visualization of the bony parts of the chest. The aim of this study was to evaluate the diagnostic accuracy of rib series in minor thorax trauma. Retrospective study of 56 patients who received RS, 39 patients where additionally evaluated by plain chest film (PCF). All patients underwent a computed tomography (CT) of the chest. RS and PCF were re-read independently by three radiologists, the results were compared with the CT as goldstandard. Sensitivity, specificity, negative and positive predictive value were calculated. Significance in the differences of findings was determined by McNemar test, interobserver variability by Cohens kappa test. 56 patients were evaluated (34 men, 22 women, mean age =61 y.). In 22 patients one or more rib fracture could be identified by CT. In 18 of these cases (82%) the correct diagnosis was made by RS, in 16 cases (73%) the correct number of involved ribs was detected. These differences were significant (p = 0.03). Specificity was 100%, negative and positive predictive value were 85% and 100%. Kappa values for the interobserver agreement was 0.92-0.96. Sensitivity of PCF was 46% and was significantly lower (p = 0.008) compared to CT. Rib series does not seem to be an useful examination in evaluating minor thorax trauma. CT seems to be the method of choice to detect rib fractures, but the clinical value of the radiological proof has to be discussed and investigated in larger follow up studies.

Raman spectroscopy reveals biophysical markers in skin cancer surgical margins

NASA Astrophysics Data System (ADS)

Feng, Xu; Moy, Austin J.; Nguyen, Hieu T. M.; Zhang, Yao; Fox, Matthew C.; Sebastian, Katherine R.; Reichenberg, Jason S.; Markey, Mia K.; Tunnell, James W.

2018-02-01

The recurrence rate of nonmelanoma skin cancer is highly related to the residual tumor after surgery. Although tissueconserving surgery, such as Mohs surgery, is a standard method for the treatment of nonmelanoma skin cancer, they are limited by lengthy and costly frozen-section histopathology. Raman spectroscopy (RS) is proving to be an objective, sensitive, and non-destructive tool for detecting skin cancer. Previous studies demonstrated the high sensitivity of RS in detecting tumor margins of basal cell carcinoma (BCC). However, those studies rely on statistical classification models and do not elucidate the skin biophysical composition. As a result, we aim to discover the biophysical differences between BCC and primary normal skin structures (including epidermis, dermis, hair follicle, sebaceous gland and fat). We obtained freshly resected ex vivo skin samples from fresh resection specimens from 14 patients undergoing Mohs surgery. Raman images were acquired from regions containing one or more structures using a custom built 830nm confocal Raman microscope. The spectra were grouped using K-means clustering analysis and annotated as either BCC or each of the five normal structures by comparing with the histopathology image of the serial section. The spectral data were then fit by a previously established biophysical model with eight primary skin constituents. Our results show that BCC has significant differences in the fit coefficients of nucleus, collagen, triolein, keratin and elastin compared with normal structures. Our study reveals RS has the potential to detect biophysical changes in resection margins, and supports the development of diagnostic algorithms for future intraoperative implementation of RS during Mohs surgery.

Using a teaching OSCE to prompt learners to engage with patients who talk about religion and/or spirituality.

PubMed

Ledford, Christy J W; Seehusen, Dean A; Canzona, Mollie Rose; Cafferty, Lauren A

2014-01-01

The objective structured clinical examination (OSCE) has only occasionally been used as a teaching tool. The authors describe the initial use of an educational innovation consisting of a teaching OSCE used as "sensitizing practice," followed by personal, guided, and group reflection. Staff and resident physicians and one medical student (N = 28) at a community hospital's family medicine residency participated in the innovation during August 2012. The initial use of the educational innovation allowed learners to engage in a potentially challenging conversation with a standardized patient about religion and/or spirituality (R/S). The aim of the innovation was not to equip learners with a particular tactic to introduce or discuss R/S but, rather, to prompt learners to engage in mindful practice with patients who identify R/S as part of their biopsychosocial contexts. Written, dyadic, and group reflection added value to the OSCE by allowing participants to reflect on a difficult learning objective over time. Participants moved along the stages-of-change continuum when engaging in guided reflection compared with personal reflection. Additionally, all participants provided evidence of at least the preparation stage at the time of guided reflection. By following the OSCE's sensitizing practice with three periods of reflection, learners were enabled first, to recognize the need for readiness to address challenging communication topics (in this case, R/S) and, second, to reflect on practiced strategies for those conversations. The educational innovation can help learners become more aware of and skillful in dealing with difficult physician-patient communication topics.

Sodium bicarbonate cotransporter NBCe2 gene variants increase sodium and bicarbonate transport in human renal proximal tubule cells.

PubMed

Gildea, John J; Xu, Peng; Kemp, Brandon A; Carlson, Julia M; Tran, Hanh T; Bigler Wang, Dora; Langouët-Astrié, Christophe J; McGrath, Helen E; Carey, Robert M; Jose, Pedro A; Felder, Robin A

2018-01-01

Salt sensitivity of blood pressure affects >30% of the hypertensive and >15% of the normotensive population. Variants of the electrogenic sodium bicarbonate cotransporter NBCe2 gene, SLC4A5, are associated with increased blood pressure in several ethnic groups. SLC4A5 variants are also highly associated with salt sensitivity, independent of hypertension. However, little is known about how NBCe2 contributes to salt sensitivity, although NBCe2 regulates renal tubular sodium bicarbonate transport. We hypothesized that SLC4A5 rs10177833 and rs7571842 increase NBCe2 expression and human renal proximal tubule cell (hRPTC) sodium transport and may be a cause of salt sensitivity of blood pressure. To characterize the hRPTC ion transport of wild-type (WT) and homozygous variants (HV) of SLC4A5. The expressions of NBCe2 mRNA and protein were not different between hRPTCs carrying WT or HV SLC4A5 before or after dopaminergic or angiotensin (II and III) stimulation. However, luminal to basolateral sodium transport, NHE3 protein, and Cl-/HCO3- exchanger activity in hRPTCs were higher in HV than WT SLC4A5. Increasing intracellular sodium enhanced the apical location of NBCe2 in HV hRPTCs (4.24±0.35% to 11.06±1.72% (P<0.05, N = 3, 2-way ANOVA, Holm-Sidak test)) as determined by Total Internal Reflection Fluorescence Microscopy (TIRFM). In hRPTCs isolated from kidney tissue, increasing intracellular sodium enhanced bicarbonate-dependent pH recovery rate and increased NBCe2 mRNA and protein expressions to a greater extent in HV than WT SLC4A5 (+38.00±6.23% vs HV normal salt (P<0.01, N = 4, 2-way ANOVA, Holm-Sidak test)). In hRPTCs isolated from freshly voided urine, bicarbonate-dependent pH recovery was also faster in those from salt-sensitive and carriers of HV SLC4A5 than from salt-resistant and carriers of WT SLC4A5. The faster NBCe2-specific bicarbonate-dependent pH recovery rate in HV SCL4A5 was normalized by SLC4A5- but not SLC4A4-shRNA. The binding of purified hepatocyte nuclear factor type 4A (HNF4A) to DNA was increased in hRPTCs carrying HV SLC4A5 rs7571842 but not rs10177833. The faster NBCe2-specific bicarbonate-dependent pH recovery rate in HV SCL4A5 was abolished by HNF4A antagonists. NBCe2 activity is stimulated by an increase in intracellular sodium and is hyper-responsive in hRPTCs carrying HV SLC4A5 rs7571842 through an aberrant HNF4A-mediated mechanism.

Impact of climate change on potential evapotranspiration under a historical and future climate scenario in the Huang-Huai-Hai Plain, China

NASA Astrophysics Data System (ADS)

Liu, Qin; Yan, Changrong; Ju, Hui; Garré, Sarah

2018-04-01

Climate change is widely accepted to be one of the most critical problems faced by the Huang-Huai-Hai Plain (3H Plain), which is a region in which there is an over-exploitation of groundwater and where future warmer and drought conditions might intensify crop water demand. In this study, the spatiotemporal patterns of ET0 and primary driving meteorological variables were investigated based on a historical and RCP 8.5 scenario daily data set from 40 weather stations over the 3H Plain using linear regression, spline interpolation method, a partial derivative analysis, and multivariate regression. The results indicated a negative trend in all the analysed periods (except spring) of the past 54 years of which only summer and the entire year were statistically significant ( p < 0.01) with slopes of -1.09 and -1.29 mm a-1, respectively. In contrast, a positive trend was observed in all four seasons and the entire year under the RCP 8.5 scenario, with the biggest increment equal to 1.36 mm a-1 in summer and an annual increment of 3.37 mm a-1. The spatial patterns of the seasonal and annual ET0 exhibited the lowest values in southeastern regions and the highest values in northeastern parts of Shandong Province, probably because of the combined effects of various meteorological variables over the past 54 years. Relative humidity (RH) together with solar radiation (RS) were detected to be the main climatic factors controlling the reduction of ET0 in summer, autumn, and the entire year on the 3H Plain. ET0 in spring was mainly sensitive to changes in RS and RH, whereas ET0 in winter was most sensitive to changes in wind speed (WS) and decreased due to declining RH. Under the future RCP 8.5 scenario, the annual ET0 distribution displays a rich spatial structure with a clear northeast-west gradient and an area with low values in the southern regions, which is similarly detected in spring and summer. The most sensitive and primary controlling variables with respect to the increment of future ET0 are in the first place RS and then mean temperature in spring, while they turn to be mean temperature and then RS in summer. In autumn, future ET0 is most sensitive to RH changes. WS and RH are the controlling variables for ET0 in winter. Annual future ET0 is most sensitive to RH changes, and accordingly, RS is responsible for the predicted increment of the annual ET0. Better understanding of current and future spatiotemporal patterns of ET0 and of the regional response of ET0 to climate change can contribute to the establishment of a policy to realize a more efficient use of water resources and a sustainable agricultural production in the 3H Plain.

The Advanced Gamma-ray Imaging System (AGIS): Simulation Studies

NASA Astrophysics Data System (ADS)

Fegan, Stephen; Buckley, J. H.; Bugaev, S.; Funk, S.; Konopelko, A.; Maier, G.; Vassiliev, V. V.; Simulation Studies Working Group; AGIS Collaboration

2008-03-01

The Advanced Gamma-ray Imaging System (AGIS) is a concept for the next generation instrument in ground-based very high energy gamma-ray astronomy. It has the goal of achieving significant improvement in sensitivity over current experiments. We present the results of simulation studies of various possible designs for AGIS. The primary characteristics of the array performance, collecting area, angular resolution, background rejection, and sensitivity are discussed.

Microchannel plate special nuclear materials sensor

NASA Astrophysics Data System (ADS)

Feller, W. B.; White, P. L.; White, P. B.; Siegmund, O. H. W.; Martin, A. P.; Vallerga, J. V.

2011-10-01

Nova Scientific Inc., is developing for the Domestic Nuclear Detection Office (DNDO SBIR #HSHQDC-08-C-00190), a solid-state, high-efficiency neutron detection alternative to 3He gas tubes, using neutron-sensitive microchannel plates (MCPs) containing 10B and/or Gd. This work directly supports DNDO development of technologies designed to detect and interdict nuclear weapons or illicit nuclear materials. Neutron-sensitized MCPs have been shown theoretically and more recently experimentally, to be capable of thermal neutron detection efficiencies equivalent to 3He gas tubes. Although typical solid-state neutron detectors typically have an intrinsic gamma sensitivity orders of magnitude higher than that of 3He gas detectors, we dramatically reduce gamma sensitivity by combining a novel electronic coincidence rejection scheme, employing a separate but enveloping gamma scintillator. This has already resulted in a measured gamma rejection ratio equal to a small 3He tube, without in principle sacrificing neutron detection efficiency. Ongoing improvements to the MCP performance as well as the coincidence counting geometry will be described. Repeated testing and validation with a 252Cf source has been underway throughout the Phase II SBIR program, with ongoing comparisons to a small commercial 3He gas tube. Finally, further component improvements and efforts toward integration maturity are underway, with the goal of establishing functional prototypes for SNM field testing.

Resistant Starch from High-Amylose Maize Increases Insulin Sensitivity in Overweight and Obese Men123

PubMed Central

Maki, Kevin C.; Pelkman, Christine L.; Finocchiaro, E. Terry; Kelley, Kathleen M.; Lawless, Andrea L.; Schild, Arianne L.; Rains, Tia M.

2012-01-01

This study evaluated the effects of 2 levels of intake of high-amylose maize type 2 resistant starch (HAM-RS2) on insulin sensitivity (SI) in participants with waist circumference ≥89 (women) or ≥102 cm (men). Participants received 0 (control starch), 15, or 30 g/d (double-blind) of HAM-RS2 in random order for 4-wk periods separated by 3-wk washouts. Minimal model SI was assessed at the end of each period using the insulin-modified i.v. glucose tolerance test. The efficacy evaluable sample included 11 men and 22 women (mean ± SEM) age 49.5 ± 1.6 y, with a BMI of 30.6 ± 0.5 kg/m2 and waist circumference 105.3 ± 1.3 cm. A treatment main effect (P = 0.018) and a treatment × sex interaction (P = 0.033) were present. In men, least squares geometric mean analysis for SI did not differ after intake of 15 g/d HAM-RS2 (6.90 × 10−5 pmol−1 · L−1 × min−1) and 30 g/d HAM-RS2 (7.13 × 10−5 pmol−1 · L−1 × min−1), but both were higher than after the control treatment (4.66 × 10−5 pmol−1 · L−1 × min−1) (P < 0.05). In women, there was no difference among the treatments (overall least squares ln-transformed mean ± pooled SEM = 1.80 ± 0.08; geometric mean = 6.05 × 10−5 pmol−1 · L−1 × min−1). These results suggest that consumption of 15–30 g/d of HAM-RS2 improves SI in men. Additional research is needed to understand the mechanisms that might account for the treatment × sex interaction observed. PMID:22357745

Soil CO2 efflux from two mountain forests in the eastern Himalayas, Bhutan: components and controls

NASA Astrophysics Data System (ADS)

Wangdi, Norbu; Mayer, Mathias; Prasad Nirola, Mani; Zangmo, Norbu; Orong, Karma; Uddin Ahmed, Iftekhar; Darabant, Andras; Jandl, Robert; Gratzer, Georg; Schindlbacher, Andreas

2017-01-01

The biogeochemistry of mountain forests in the Hindu Kush Himalaya range is poorly studied, although climate change is expected to disproportionally affect the region. We measured the soil CO2 efflux (Rs) at a high-elevation (3260 m) mixed forest and a lower-elevation (2460 m) broadleaf forest in Bhutan, eastern Himalayas, during 2015. Trenching was applied to estimate the contribution of autotrophic (Ra) and heterotrophic (Rh) soil respiration. The temperature (Q10) and the moisture sensitivities of Rh were determined under controlled laboratory conditions and were used to model Rh in the field. The higher-elevation mixed forest had a higher standing tree stock, reflected in higher soil C stocks and basal soil respiration. Annual Rs was similar between the two forest sites (14.5 ± 1.2 t C ha-1 for broadleaf; 12.8 ± 1.0 t C ha-1 for mixed). Modelled annual contribution of Rh was ˜ 65 % of Rs at both sites with a higher heterotrophic contribution during winter and lower contribution during the monsoon season. Rh, estimated from trenching, was in the range of modelled Rh but showed higher temporal variability. The measured temperature sensitivity of Rh was similar at the mixed and broadleaf forest sites (Q10 2.2-2.3) under intermediate soil moisture but decreased (Q10 1.5 at both sites) in dry soil. Rs closely followed the annual course of field soil temperature at both sites. Covariation between soil temperature and moisture (cold dry winters and warm wet summers) was likely the main cause for this close relationship. Under the prevailing weather conditions, a simple temperature-driven model was able to explain more than 90 % of the temporal variation in Rs. A longer time series and/or experimental climate manipulations are required to understand the effects of eventually occurring climate extremes such as monsoon failures.

Nicotine and ethanol cooperate to enhance ventral tegmental area AMPA receptor function via α6-containing nicotinic receptors.

PubMed

Engle, Staci E; McIntosh, J Michael; Drenan, Ryan M

2015-04-01

Nicotine + ethanol co-exposure results in additive and/or synergistic effects in the ventral tegmental area (VTA) to nucleus accumbens (NAc) dopamine (DA) pathway, but the mechanisms supporting this are unclear. We tested the hypothesis that nAChRs containing α6 subunits (α6* nAChRs) are involved in the response to nicotine + ethanol co-exposure. Exposing VTA slices from C57BL/6 WT animals to drinking-relevant concentrations of ethanol causes a marked enhancement of α-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA) receptor (AMPAR) function in VTA neurons. This effect was sensitive to α-conotoxin MII (an α6β2* nAChR antagonist), suggesting that α6* nAChR function is required. In mice expressing hypersensitive α6* nAChRs (α6L9S mice), we found that lower concentrations (relative to C57BL/6 WT) of ethanol were sufficient to enhance AMPAR function in VTA neurons. Exposure of live C57BL/6 WT mice to ethanol also produced AMPAR functional enhancement in VTA neurons, and studies in α6L9S mice strongly suggest a role for α6* nAChRs in this response. We then asked whether nicotine and ethanol cooperate to enhance VTA AMPAR function. We identified low concentrations of nicotine and ethanol that were capable of strongly enhancing VTA AMPAR function when co-applied to slices, but that did not enhance AMPAR function when applied alone. This effect was sensitive to both varenicline (an α4β2* and α6β2* nAChR partial agonist) and α-conotoxin MII. Finally, nicotine + ethanol co-exposure also enhanced AMPAR function in VTA neurons from α6L9S mice. Together, these data identify α6* nAChRs as important players in the response to nicotine + ethanol co-exposure in VTA neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

Social Interpretation Bias in Children and Adolescents with Anxiety Disorders: Psychometric Examination of the Self-report of Ambiguous Social Situations for Youth (SASSY) Scale.

PubMed

Gonzalez, Araceli; Rozenman, Michelle; Langley, Audra K; Kendall, Philip C; Ginsburg, Golda S; Compton, Scott; Walkup, John T; Birmaher, Boris; Albano, Anne Marie; Piacentini, John

2017-06-01

Anxiety disorders are among the most common mental health problems in youth, and faulty interpretation bias has been positively linked to anxiety severity, even within anxiety-disordered youth. Quick, reliable assessment of interpretation bias may be useful in identifying youth with certain types of anxiety or assessing changes on cognitive bias during intervention. This study examined the factor structure, reliability, and validity of the Self-report of Ambiguous Social Situations for Youth (SASSY) scale, a self-report measure developed to assess interpretation bias in youth. Participants (N=488, age 7 to 17) met diagnostic criteria for Social Phobia, Generalized Anxiety Disorder, and/or Separation Anxiety Disorder. An exploratory factor analysis was performed on baseline data from youth participating in a large randomized clinical trial. Exploratory factor analysis yielded two factors (Accusation/Blame, Social Rejection). The SASSY full scale and Social Rejection factor demonstrated adequate internal consistency, convergent validity with social anxiety, and discriminant validity as evidenced by non-significant correlations with measures of non-social anxiety. Further, the SASSY Social Rejection factor accurately distinguished children and adolescents with Social Phobia from those with other anxiety disorders, supporting its criterion validity, and revealed sensitivity to changes with treatment. Given the relevance to youth with social phobia, pre- and post-intervention data were examined for youth social phobia to test sensitivity to treatment effects; results suggested that SASSY scores reduced for treatment responders. Findings suggest the potential utility of the SASSY Social Rejection factor as a quick, reliable, and efficient way of assessing interpretation bias in anxious youth, particularly as related to social concerns, in research and clinical settings.

Outcomes of Highly Sensitized Patients Undergoing Simultaneous Liver and Kidney Transplantation: A Single-Center Experience With Desensitization.

PubMed

Steggerda, J A; Kang, A; Pan, S-H; Sundaram, V; Nissen, N N; Klein, A S; Todo, T; Annamalai, A; Vo, A; Jordan, S C; Kim, I K

Preformed donor-specific human leukocyte antigen antibodies (DSAs) in patients undergoing simultaneous liver and kidney transplantation (SLKT) are an independent risk factor for poorer patient and renal allograft survival. The outcomes of patients highly sensitized (HS) against HLA antigens undergoing SLKT and select HS SLKT recipients undergoing desensitization at a high-volume desensitization center were investigated. Seventy-five patients undergoing SLKT at a high-volume desensitization center between January 1, 2001, and December 31, 2015, were retrospectively reviewed. HS patients were defined by panel-reactive antibody (PRA) >30% (n = 17 patients), 11 of whom received pre- or perioperative desensitization with high-dose intravenous immunoglobulin (IVIG) ± rituximab. HS patients had significantly higher class I and class II PRA (class I = 41.3% ± 40.0% vs 2.5% ± 6.3%; class II = 45.7% ± 36.4% vs 1.0% ± 2.9%; P < .001), were more likely to be female (P = .05), and more likely to have had a prior transplant (P = .03). HS patients demonstrated greater susceptibility to renal cell-mediated rejection (CMR) (23.5% vs 5.2%, P = .02) compared to nonsensitized patients. Higher renal antibody-mediated rejection (ABMR) was also observed in HS patients, 11.8% vs 3.4%, but did not reach significance (P = .18). Desensitization in select HS SLKT patients was well tolerated but did not improve patient and allograft survival or significantly curtail rejection. HS SLKT recipients demonstrated increased allograft rejection, particularly CMR, but patient and graft survival were not impacted in the first year post-transplant. Select HS SLKT patients tolerated desensitization with high-dose IVIG ± rituximab and may have received additional immunoprotection against ABMR but survival was not affected. Copyright © 2017 Elsevier Inc. All rights reserved.

Improved spatial resolution in PET scanners using sampling techniques

PubMed Central

Surti, Suleman; Scheuermann, Ryan; Werner, Matthew E.; Karp, Joel S.

2009-01-01

Increased focus towards improved detector spatial resolution in PET has led to the use of smaller crystals in some form of light sharing detector design. In this work we evaluate two sampling techniques that can be applied during calibrations for pixelated detector designs in order to improve the reconstructed spatial resolution. The inter-crystal positioning technique utilizes sub-sampling in the crystal flood map to better sample the Compton scatter events in the detector. The Compton scatter rejection technique, on the other hand, rejects those events that are located further from individual crystal centers in the flood map. We performed Monte Carlo simulations followed by measurements on two whole-body scanners for point source data. The simulations and measurements were performed for scanners using scintillators with Zeff ranging from 46.9 to 63 for LaBr3 and LYSO, respectively. Our results show that near the center of the scanner, inter-crystal positioning technique leads to a gain of about 0.5-mm in reconstructed spatial resolution (FWHM) for both scanner designs. In a small animal LYSO scanner the resolution improves from 1.9-mm to 1.6-mm with the inter-crystal technique. The Compton scatter rejection technique shows higher gains in spatial resolution but at the cost of reduction in scanner sensitivity. The inter-crystal positioning technique represents a modest acquisition software modification for an improvement in spatial resolution, but at a cost of potentially longer data correction and reconstruction times. The Compton scatter rejection technique, while also requiring a modest acquisition software change with no increased data correction and reconstruction times, will be useful in applications where the scanner sensitivity is very high and larger improvements in spatial resolution are desirable. PMID:19779586

Soluble CD30 and ELISA-detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients.

PubMed

Billing, Heiko; Sander, Anja; Süsal, Caner; Ovens, Jörg; Feneberg, Reinhard; Höcker, Britta; Vondrak, Karel; Grenda, Ryszard; Friman, Stybjorn; Milford, David V; Lucan, Mihai; Opelz, Gerhard; Tönshoff, Burkhard

2013-03-01

Biomarker-based post-transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well-controlled prospective randomized trial was analyzed pre- and post-transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T-cell reactivity, and anti-human leukocyte antigen (anti-HLA) antibody reactivity, a biomarker for B-cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy-proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut-off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut-off (P = 0.004). For pre- and post-transplant anti-HLA class II reactivities by enzyme-linked immunosorbent assay, a cut-off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti-HLA reactivities. An increased post-transplant sCD30 serum concentration and positive pre- and post-transplant anti-HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG-506-02-43). © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

21 CFR 211.165 - Testing and release for distribution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... products meet each appropriate specification and appropriate statistical quality control criteria as a condition for their approval and release. The statistical quality control criteria shall include appropriate acceptance levels and/or appropriate rejection levels. (e) The accuracy, sensitivity, specificity, and...

Using Television Commercials to Develop Reading Comprehension.

ERIC Educational Resources Information Center

Bowman, James D.; Bowman, S. Ray

1991-01-01

Suggests that teachers can use reluctant readers' sensitivity to and sophistication with "musicomedy" to both assess and develop reading comprehension. Discusses several class activities using the musical and humorous expressions in television commercials for fulfilling this objective. (RS)

Spectrophotometric total reducing sugars assay based on cupric reduction.

PubMed

Başkan, Kevser Sözgen; Tütem, Esma; Akyüz, Esin; Özen, Seda; Apak, Reşat

2016-01-15

As the concentration of reducing sugars (RS) is controlled by European legislation for certain specific food and beverages, a simple and sensitive spectrophotometric method for the determination of RS in various food products is proposed. The method is based on the reduction of Cu(II) to Cu(I) with reducing sugars in alkaline medium in the presence of 2,9-dimethyl-1,10-phenanthroline (neocuproine: Nc), followed by the formation of a colored Cu(I)-Nc charge-transfer complex. All simple sugars tested had the linear regression equations with almost equal slope values. The proposed method was successfully applied to fresh apple juice, commercial fruit juices, milk, honey and onion juice. Interference effect of phenolic compounds in plant samples was eliminated by a solid phase extraction (SPE) clean-up process. The method was proven to have higher sensitivity and precision than the widely used dinitrosalicylic acid (DNS) colorimetric method. Copyright © 2015 Elsevier B.V. All rights reserved.

The RAD24 (= Rs1) Gene Product of Saccharomyces cerevisiae Participates in Two Different Pathways of DNA Repair

PubMed Central

Eckardt-Schupp, Friederike; Siede, Wolfram; Game, John C.

1987-01-01

The moderately UV- and X-ray-sensitive mutant of Saccharomyces cerevisiae originally designated rs1 complements all rad and mms mutants available. Therefore, the new nomination rad24-1 according to the RAD nomenclature is suggested. RAD24 maps on chromosome V, close to RAD3 (1.3 cM). In order to associate the RAD24 gene with one of the three repair pathways, double mutants of rad24 and various representative genes of each pathway were constructed. The UV and X-ray sensitivities of the double mutants compared to the single mutants indicate that RAD24 is involved in excision repair of UV damage (RAD3 epistasis group), as well as in recombination repair of UV and X-ray damage (RAD52 epistasis group). Properties of the mutant are discussed which hint at the control of late steps in the pathways. PMID:3549445

Dissociation of thirst and sodium appetite in the furo/cap model of extracellular dehydration and a role for N-methyl-D-aspartate receptors in the sensitization of sodium appetite

PubMed Central

Hurley, Seth. W.; Johnson, Alan Kim

2015-01-01

Depletion of extracellular fluids motivates many animals to seek out and ingest water and sodium. Animals with a history of extracellular dehydration display enhanced sodium appetite and in some cases thirst. The progressive increase in sodium intake induced by repeated sodium depletions is known as sensitization of sodium appetite. Administration of the diuretic and natriuretic drug, furosemide, along with a low dose of captopril (furo/cap), elicits thirst and a rapid onset of sodium appetite. In the present studies the furo/cap model was used to explore the physiological mechanisms of sensitization of sodium appetite. However, when thirst and sodium appetite were measured concurrently in the furo/cap model, individual rats exhibited sensitization of either thirst or sodium appetite. In subsequent studies, thirst and sodium appetite were dissociated by offering either water prior to sodium or sodium before water. When water and sodium intake were dissociated in time, the furo/cap model reliably produced sensitization of sodium appetite. It is likely that neuroplasticity mediates this sensitization. Glutamatergic N-methyl-d-aspartate receptor (NMDA-R) activation is critical for the development of most forms of neuroplasticity. Therefore, we hypothesized that integrity of NMDA-R function is necessary for the sensitization of sodium appetite. Pharmacological blockade of NMDA-Rs with systemic administration of MK-801 (0.15mg/kg) prevented the sensitization of fluid intake in general when water and sodium were offered concurrently, and prevented sensitization of sodium intake specifically when water and sodium intake were dissociated. The involvement of NMDA-Rs provides support for the possibility that sensitization of sodium appetite is mediated by neuroplasticity. PMID:24341713

The Credibility Revolution in Empirical Economics: How Better Research Design is Taking the Con out of Econometrics. NBER Working Paper No. 15794

ERIC Educational Resources Information Center

Angrist, Joshua; Pischke, Jorn-Steffen

2010-01-01

This essay reviews progress in empirical economics since Leamer'rs (1983) critique. Leamer highlighted the benefits of sensitivity analysis, a procedure in which researchers show how their results change with changes in specification or functional form. Sensitivity analysis has had a salutary but not a revolutionary effect on econometric practice.…

Breastfeeding and its relation to maternal sensitivity and infant attachment.

PubMed

Tharner, Anne; Luijk, Maartje P C M; Raat, Hein; Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J; Moll, Henriette A; Jaddoe, Vincent W V; Hofman, Albert; Verhulst, Frank C; Tiemeier, Henning

2012-06-01

To examine the association of breastfeeding with maternal sensitive responsiveness and infant-mother attachment security and disorganization. We included 675 participants of a prospective cohort study. Questionnaires about breastfeeding practices were administered at 2 and 6 months postpartum. At 14 months, maternal sensitive responsiveness was assessed in a 13-minute laboratory procedure using Ainsworth's sensitivity scales, and attachment quality was assessed with the Strange Situation Procedure. Mothers were genotyped for oxytocin receptor genes OXTR rs53576 and OXTR rs2254298. Linear regressions and analyses of covariance adjusted for various background variables were conducted. We tested for mediation and moderation by maternal sensitive responsiveness and maternal oxytocin receptor genotype. Continuous analyses showed that longer duration of breastfeeding was associated with more maternal sensitive responsiveness (B = 0.11, 95% confidence interval [CI] 0.02; 0.20, p < .05), more attachment security (B = 0.24, 95% CI = 0.02; 0.46, p < .05), and less attachment disorganization (B = -0.20, 95% CI -0.36; -0.03, p < .05). Duration of breastfeeding was not related to the risk of insecure-avoidant or insecure-resistant versus secure attachment classification, but longer duration of breastfeeding predicted a lower risk of disorganized versus secure attachment classification (n = 151; odds ratio [OR] = 0.81, 95% CI 0.66 to 0.99, p = .04). Maternal sensitive responsiveness did not mediate the associations, and maternal oxytocin receptor genotype was not a significant moderator. Although duration of breastfeeding was not associated with differences in infant-mother attachment classifications, we found subtle positive associations between duration of breastfeeding and sensitive responsiveness, attachment security, and disorganization.

Arbuscular mycorrhizal fungi enhance soil carbon sequestration in the coalfields, northwest China

NASA Astrophysics Data System (ADS)

Wang, Zhi-Gang; Bi, Yin-Li; Jiang, Bin; Zhakypbek, Yryszhan; Peng, Su-Ping; Liu, Wen-Wen; Liu, Hao

2016-10-01

Carbon storage is affected by photosynthesis (Pn) and soil respiration (Rs), which have been studied extensively in natural and agricultural systems. However, the effects of Pn and Rs on carbon storages in the presence of arbuscular mycorrhizal fungi (AMF) in coalfields remain unclear. A field experiment was established in 2014 in Shendong coal mining subsidence area. The treatments comprised two inoculation levels (inoculated with or without 100 g AMF inoculums per seedlings) and four plant species [wild cherry (Prunus discadenia Koebne L.), cerasus humilis (Prunus dictyneura Diels L.), shiny leaf Yellow horn (Xanthoceras sorbifolium Bunge L.) and apricot (Armeniaca sibirica L.)]. AMF increased Pn of four species ranging from 15.3% to 33.1% and carbon storage, averaged by 17.2% compared to controls. Soil organic carbon (OC), easily extractable glomalin-relation soil protein (EE-GRSP), and total glomalin-relation soil protein (T-GRSP) were significantly increased by AMF treatment. The effect of AMF on the sensitivity of Rs depended on soil temperature. The results highlighted the exponential models to explain the responses of Rs to soil temperature, and for the first time quantified AMF caused carbon sequestration and Rs. Thus, to our knowledge, AMF is beneficial to ecosystems through facilitating carbon conservation in coalfield soils.

Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI study.

PubMed

Agosta, Federica; Caso, Francesca; Ječmenica-Lukić, Milica; Petrović, Igor N; Valsasina, Paola; Meani, Alessandro; Copetti, Massimiliano; Kostić, Vladimir S; Filippi, Massimo

2018-01-18

In this prospective, longitudinal, multiparametric MRI study, we investigated clinical as well as brain grey matter and white matter (WM) regional changes in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). Twenty-one patients with PSP-RS were evaluated at baseline relative to 36 healthy controls and after a mean follow-up of 1.4 years with clinical rating scales, neuropsychological tests and MRI scans. Relative to controls, patients with PSP-RS showed at baseline a typical pattern of brain damage, including midbrain atrophy, frontal cortical thinning and widespread WM involvement of the main infratentorial and supratentorial tracts that exceeded cortical damage. Longitudinal study showed that PSP-RS exhibited no further changes in cortical thinning, which remained relatively focal, while midbrain atrophy and WM damage significantly progressed. Corpus callosum and frontal WM tract changes correlated with the progression of both disease severity and behavioural dysfunction. This study demonstrated the feasibility of carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its sensitivity to identifying the progression of pathology. Longitudinal midbrain volume loss and WM changes are associated with PSP disease course. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Perfusion information extracted from resting state functional magnetic resonance imaging.

PubMed

Tong, Yunjie; Lindsey, Kimberly P; Hocke, Lia M; Vitaliano, Gordana; Mintzopoulos, Dionyssios; Frederick, Blaise deB

2017-02-01

It is widely known that blood oxygenation level dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) is an indirect measure for neuronal activations through neurovascular coupling. The BOLD signal is also influenced by many non-neuronal physiological fluctuations. In previous resting state (RS) fMRI studies, we have identified a moving systemic low frequency oscillation (sLFO) in BOLD signal and were able to track its passage through the brain. We hypothesized that this seemingly intrinsic signal moves with the blood, and therefore, its dynamic patterns represent cerebral blood flow. In this study, we tested this hypothesis by performing Dynamic Susceptibility Contrast (DSC) MRI scans (i.e. bolus tracking) following the RS scans on eight healthy subjects. The dynamic patterns of sLFO derived from RS data were compared with the bolus flow visually and quantitatively. We found that the flow of sLFO derived from RS fMRI does to a large extent represent the blood flow measured with DSC. The small differences, we hypothesize, are largely due to the difference between the methods in their sensitivity to different vessel types. We conclude that the flow of sLFO in RS visualized by our time delay method represents the blood flow in the capillaries and veins in the brain.

Effects of Soil Temperature and Moisture on Soil Respiration on the Tibetan Plateau

PubMed Central

Chang, Xiaofeng; Wang, Shiping; Xu, Burenbayin; Luo, Caiyun; Zhang, Zhenhua; Wang, Qi; Rui, Yichao; Cui, Xiaoying

2016-01-01

Understanding of effects of soil temperature and soil moisture on soil respiration (Rs) under future warming is critical to reduce uncertainty in predictions of feedbacks to atmospheric CO2 concentrations from grassland soil carbon. Intact cores with roots taken from a full factorial, 5-year alpine meadow warming and grazing experiment in the field were incubated at three different temperatures (i.e. 5, 15 and 25°C) with two soil moistures (i.e. 30 and 60% water holding capacity (WHC)) in our study. Another experiment of glucose-induced respiration (GIR) with 4 h of incubation was conducted to determine substrate limitation. Our results showed that high temperature increased Rs and low soil moisture limited the response of Rs to temperature only at high incubation temperature (i.e. 25°C). Temperature sensitivity (Q10) did not significantly decrease over the incubation period, suggesting that substrate depletion did not limit Rs. Meanwhile, the carbon availability index (CAI) was higher at 5°C compared with 15 and 25°C incubation, but GIR increased with increasing temperature. Therefore, our findings suggest that warming-induced decrease in Rs in the field over time may result from a decrease in soil moisture rather than from soil substrate depletion, because warming increased root biomass in the alpine meadow. PMID:27798671

A Novel Multiplex HRM Assay to Detect Clopidogrel Resistance.

PubMed

Zhang, Lichen; Ma, Xiaowei; You, Guoling; Zhang, Xiaoqing; Fu, Qihua

2017-11-22

Clopidogrel is an antiplatelet medicine used to prevent blood clots in patients who have had a heart attack, stroke, or other symptoms. Variability in the clinical response to clopidogrel treatment has been attributed to genetic factors. In particular, five SNPs of rs4244285, rs4986893, rs12248560, rs662 and rs1045642 have been associated with resistance to clopidogrel therapy in Chinese population. This work involves the development of a multiplex high-resolution melting (HRM) assay to genotype all five of these loci in 2 tubes. Amplicons corresponding to distinct SNPs in a common tube were designed with the aid of uMelt prediction software to have different melting temperatures Tm by addition of a GC-rich tail to the 5' end of the certain primers. Two kinds of commercial methods, Digital Fluorescence Molecular Hybridization (DFMH) and Sanger sequencing, were used as a control. Three hundred sixteen DFMH pretested samples from consecutive acute coronary syndrome patients were used for a blinded study of multiplex HRM. The sensitivity of HRM was 100% and the specificity was 99.93% reflecting detection of variants other than the known resistance SNPs. Multiplex HRM is an effective closed-tube, highly accurate, fast, and inexpensive method for genotyping the 5 clopidogrel resistance associated SNPs.

S100A8 protein attenuates airway hyperresponsiveness by suppressing the contraction of airway smooth muscle.

PubMed

Xu, Yu-Dong; Wang, Yu; Yin, Lei-Miao; Park, Gyoung-Hee; Ulloa, Luis; Yang, Yong-Qing

2017-02-26

Airway hyperresponsiveness (AHR) is a major clinical problem in allergic asthma mainly caused by the hypercontractility of airway smooth muscles (ASM). S100A8 is an important member of the S100 calcium-binding protein family with a potential to regulate cell contractility. Here, we analyze the potential of S100A8 to regulate allergen-induced AHR and ASM contraction. Treatment with recombinant S100A8 (rS100A8) diminished airway hyperresponsiveness in OVA-sensitized rats. ASM contraction assays showed that rS100A8 reduced hypercontractility in both isolated tracheal rings and primary ASM cells treated by acetylcholine. rS100A8 markedly rescued the phosphorylation level of myosin light chain induced by acetylcholine in ASM cells. These results show that rS100A8 plays a protective role in regulating AHR in asthma by inhibiting ASM contraction. These results support S100A8 as a novel therapeutic target to control ASM contraction in asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The impact of a parkinsonian lesion on dynamic striatal dopamine transmission depends on nicotinic receptor activation

PubMed Central

Jennings, Katie A.; Platt, Nicola J.; Cragg, Stephanie J.

2015-01-01

Dopamine function is disturbed in Parkinson's disease (PD), but whether and how release of dopamine from surviving neurons is altered has long been debated. Nicotinic acetylcholine receptors (nAChRs) on dopamine axons powerfully govern dopamine release and could be critical contributing factors. We revisited whether fundamental properties of dopamine transmission are changed in a parkinsonian brain and tested the potentially profound masking effects of nAChRs. Using real-time detection of dopamine in mouse striatum after a partial 6-hydroxydopamine lesion and under nAChR inhibition, we reveal that dopamine signals show diminished sensitivity to presynaptic activity. This effect manifested as diminished contrast between DA release evoked by the lowest versus highest frequencies. This reduced activity-dependence was underpinned by loss of short-term facilitation of dopamine release, consistent with an increase in release probability (Pr). With nAChRs active, the reduced activity-dependence of dopamine release after a parkinsonian lesion was masked. Consequently, moment-by-moment variation in activity of nAChRs may lead to dynamic co-variation in dopamine signal impairments in PD. PMID:26117304

Effects of fibers and fabrication processes on mechanical properties of neutron irradiated SiC/SiC composites

NASA Astrophysics Data System (ADS)

Nozawa, T.; Hinoki, T.; Katoh, Y.; Kohyama, A.

2002-12-01

Radiation effects on flexural properties of SiC/SiC composites fabricated by forced thermal gradient chemical vapor infiltration (F-CVI) process, reaction sintered (RS) process and polymer impregnation and pyrolysis (PIP) process were investigated. In this study, neutron irradiation at 1073 K up to 0.4×10 25 n/m 2 ( E>0.1 MeV) was performed. For F-CVI and RS SiC/SiC, due to the irradiation damage of interphase like pyrolytic carbon and boron nitride, which were sensitive to neutron irradiation, composite stiffness was slightly decreased. On the contrary, for PIP SiC/SiC, there was no significant change in stiffness before and after irradiation. Composite strength, however, was nearly stable against high-temperature irradiation with such a low fluence, except for RS SiC/SiC, since mechanical characteristics of fiber and matrix themselves were still stable to neutron irradiation. However RS SiC/SiC had a slight reduction of flexural strength due to the severe degradation of the interface by neutron irradiation.

Glucocorticoid Receptor Polymorphisms and Outcomes in Pediatric Septic Shock.

PubMed

Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Grunwell, Jocelyn R; Opoka, Amy; Wong, Hector R

2017-04-01

Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock. We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids. The primary outcome variable was complicated course, defined as 28-day mortality or the persistence of two or more organ failures 7 days after a septic shock diagnosis. We used logistic regression to test for an association between corticosteroid exposure and outcome, within genotype group, and adjusted for illness severity. Multiple PICUs in the United States. Standard care. There were no differences in outcome when comparing the various genotype groups. Among patients homozygous for the wild-type glucocorticoid receptor allele, corticosteroids were independently associated with increased odds of complicated course (odds ratio, 2.30; 95% CI, 1.01-5.21; p = 0.047). Based on these glucocorticoid receptor polymorphisms, we could not detect a beneficial effect of corticosteroids among any genotype group. Among children homozygous for the wild-type allele, corticosteroids were independently associated with increased odds of poor outcome.

Laboratory, clinical and therapeutic features of respiratory panic disorder subtype.

PubMed

Zugliani, Morena M; Freire, Rafael C; Perna, Giampaolo; Crippa, Jose A; Nardi, Antonio E

2015-01-01

It is our aim to elaborate on the new developments in regard to the respiratory subtype (RS) of panic disorder (PD) since it was first described. We will present psychopathological features, diagnostic criteria, genetic and physiopathological hypotheses, as well as therapeutic and prognostic characteristics. Two searches were performed in the Thomson Reuters Web of Knowledge (http://wokinfo.com/): 1 - search terms: "panic disorder" AND ("respiratory symptom" OR "respiratory symptoms" OR "respiratory subtype" OR "respiratory panic" OR "cardiorespiratory"); 2 - all articles citing Briggs and colleagues' 1993 article "Subtyping of Panic Disorder by Symptom Profile" (Br J Psychiatry 1993;163: 201-9). Only those articles involving human subjects and written English were included. In comparison with patients of the non-respiratory subtype (NRS), RS patients showed greater familial history of PD, and higher comorbidity rates for anxiety disorders and depressive disorders. These patients were also more sensitive to CO2, hyperventilation and caffeine. Certain characteristics, such as heightened sensitivity to CO2 and the higher incidence of a family history of PD, clearly distinguished the Respiratory Subtype patients from the Non-Respiratory. Nonetheless, some studies failed to demonstrate differential responses to pharmacological treatment and CBT across the subtypes. RS patients seem to respond faster than NRS to pharmacological treatment with antidepressants and benzodiazepines, but more studies are needed to confirm this finding.

Dynamic Responses in Brain Networks to Social Feedback: A Dual EEG Acquisition Study in Adolescent Couples

PubMed Central

Kuo, Ching-Chang; Ha, Thao; Ebbert, Ashley M.; Tucker, Don M.; Dishion, Thomas J.

2017-01-01

Adolescence is a sensitive period for the development of romantic relationships. During this period the maturation of frontolimbic networks is particularly important for the capacity to regulate emotional experiences. In previous research, both functional magnetic resonance imaging (fMRI) and dense array electroencephalography (dEEG) measures have suggested that responses in limbic regions are enhanced in adolescents experiencing social rejection. In the present research, we examined social acceptance and rejection from romantic partners as they engaged in a Chatroom Interact Task. Dual 128-channel dEEG systems were used to record neural responses to acceptance and rejection from both adolescent romantic partners and unfamiliar peers (N = 75). We employed a two-step temporal principal component analysis (PCA) and spatial independent component analysis (ICA) approach to statistically identify the neural components related to social feedback. Results revealed that the early (288 ms) discrimination between acceptance and rejection reflected by the P3a component was significant for the romantic partner but not the unfamiliar peer. In contrast, the later (364 ms) P3b component discriminated between acceptance and rejection for both partners and peers. The two-step approach (PCA then ICA) was better able than either PCA or ICA alone in separating these components of the brain's electrical activity that reflected both temporal and spatial phases of the brain's processing of social feedback. PMID:28620292

Prediction of acute renal allograft rejection in early post-transplantation period by soluble CD30.

PubMed

Dong, Wang; Shunliang, Yang; Weizhen, Wu; Qinghua, Wang; Zhangxin, Zeng; Jianming, Tan; He, Wang

2006-06-01

To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P < 0.001). Compared with Group UC and DGF, patients of Group AR had higher sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P < 0.001). However, sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

Has Metal-On-Metal Resurfacing Been a Cost-Effective Intervention for Health Care Providers?-A Registry Based Study.

PubMed

Pulikottil-Jacob, Ruth; Connock, Martin; Kandala, Ngianga-Bakwin; Mistry, Hema; Grove, Amy; Freeman, Karoline; Costa, Matthew; Sutcliffe, Paul; Clarke, Aileen

2016-01-01

Total hip replacement for end stage arthritis of the hip is currently the most common elective surgical procedure. In 2007 about 7.5% of UK implants were metal-on-metal joint resurfacing (MoM RS) procedures. Due to poor revision performance and concerns about metal debris, the use of RS had declined by 2012 to about a 1% share of UK hip procedures. This study estimated the lifetime cost-effectiveness of metal-on-metal resurfacing (RS) procedures versus commonly employed total hip replacement (THR) methods. We performed a cost-utility analysis using a well-established multi-state semi-Markov model from an NHS and personal and social services perspective. We used individual patient data (IPD) from the National Joint Registry (NJR) for England and Wales on RS and THR surgery for osteoarthritis recorded from April 2003 to December 2012. We used flexible parametric modelling of NJR RS data to guide identification of patient subgroups and RS devices which delivered revision rates within the NICE 5% revision rate benchmark at 10 years. RS procedures overall have an estimated revision rate of 13% at 10 years, compared to <4% for most THR devices. New NICE guidance now recommends a revision rate benchmark of <5% at 10 years. 60% of RS implants in men and 2% in women were predicted to be within the revision benchmark. RS devices satisfying the 5% benchmark were unlikely to be cost-effective compared to THR at a standard UK willingness to pay of £20,000 per quality-adjusted life-year. However, the probability of cost effectiveness was sensitive to small changes in the costs of devices or in quality of life or revision rate estimates. Our results imply that in most cases RS has not been a cost-effective resource and should probably not be adopted by decision makers concerned with the cost effectiveness of hip replacement, or by patients concerned about the likelihood of revision, regardless of patient age or gender.

First-ever ischemic stroke in elderly patients: predictors of functional outcome following carotid artery stenting

PubMed Central

Lin, Chih-Ming; Chang, Yu-Jun; Liu, Chi-Kuang; Yu, Cheng-Sheng; Lu, Henry Horng-Shing

2016-01-01

Age is an important risk factor for stroke, and carotid artery stenosis is the primary cause of first-ever ischemic stroke. Timely intervention with stenting procedures can effectively prevent secondary stroke; however, the impact of stenting on various periprocedural physical functionalities has never been thoroughly investigated. The primary aim of this study was to investigate whether prestenting characteristics were associated with long-term functional outcomes in patients presenting with first-ever ischemic stroke. The secondary aim was to investigate whether patient age was an important factor in outcomes following stenting, measured by the modified Rankin scale (mRS). In total, 144 consecutive patients with first-ever ischemic stroke who underwent carotid artery stenting from January 2010 to November 2014 were included. Clinical data were obtained by review of medical records. The Barthel index (BI) and mRS were used to assess disability before stenting and at 12-month follow-up. In total, 72/144 patients showed improvement (mRS[+]), 71 showed stationary and one showed deterioration in condition (mRS[−]). The prestenting parameters, ratio of cerebral blood volume (1.41 vs 1.2 for mRS[−] vs mRS[+]), BI (75 vs 85), and high-sensitivity C-reactive protein (hsCRP 5.0 vs 3.99), differed significantly between the two outcome groups (P<0.05). The internal carotid artery/common carotid artery ratio (P=0.011), BI (P=0.019), ipsilateral internal carotid artery resistance index (P=0.003), and HbA1c (P=0.039) were all factors significantly associated with patient age group. There was no significant association between age and poststenting outcome measured by mRS with 57% of patients in the ≥75 years age group showing mRS(−) and 43% showing mRS(+) (P=0.371). Our findings indicate that in our elderly patient series, carotid artery stenting may benefit a significant proportion of carotid stenotic patients regardless of age. Ratio of cerebral blood volume, BI, and admission hsCRP could serve as important predictors of mRS improvement and may facilitate differentiation of patients at baseline. PMID:27555753

[Association between patatin-like phospholipase domain-containing protein 3 gene rs738409 polymorphism and non-alcoholic fatty liver disease susceptibility: a meta-analysis].

PubMed

Wu, Pengbo; Shu, Yongxiang; Guo, Fang; Luo, Hesheng; Zhang, Guo; Tan, Shiyun

2015-01-01

To explore the association between patatin-like phospholipase domain-containing protein 3(PNPLA3) gene rs738409 polymorphism and the susceptibility of non-alcoholic fatty liver disease(NAFLD). Data bases were comprehensively searched to retrace all the related studies on the association between PNPLA3 gene rs738409 polymorphism and susceptibility. Of NAFLD, the pooled OR with 95% CI of the association between PNPLA3 gene rs738409 polymorphism and NAFLD susceptibility were performed using different genetic models. Subgroup analysis based on the source of population and sensitivity analysis was performed to detect the stability of results. 28 original studies with 6 216 patients and 8 218 controls were involved in the final combination of data. Findings from the meta-analyses showed that there were strong associations between PNPLA3 gene rs738409 polymorphism and the susceptibility of NAFLD, under different genetic model comparisons[GG vs. CC:OR = 2.42, 95%CI:1.83-3.21, P < 0.001;CG vs. CC:OR = 1.28, 95%CI:1.15-1.43, P < 0.001;CG+GG vs. CC:OR = 1.31, 95%CI:1.17-1.46, P < 0.001; GG vs. CC+GC:OR = 2.26, 95%CI:1.76-2.90, P < 0.001]. Similar results were found in both Asian and Caucasian populations. Results from the Meta-analysis strongly suggested that there appeared significant association between PNPLA3 gene rs738409 polymorphism and the susceptibility of NAFLD.

Lack of association between SREBF-1c gene polymorphisms and risk of non-alcoholic fatty liver disease in a Chinese Han population.

PubMed

Peng, Xian-E; Chen, Feng-Lin; Liu, Wenjuan; Hu, ZhiJian; Lin, Xu

2016-08-30

The transcription factor sterol regulatory element-binding protein-1c (SREBP-1c) is a key regulator of lipogenesis and insulin sensitivity, and is associated with non-alcoholic fatty liver disease (NAFLD). Here, we assessed the impact of common single nucleotide polymorphisms (SNPs) in SREBF-1c on NAFLD susceptibility and associated metabolic phenotypes in a Han Chinese population. Four common SNPs (rs62064119, rs2297508, rs11868035 and rs13306741) in the SREBP-1c gene were selected and genotyped in 593 patients with NAFLD and 593 healthy controls. Unconditional logistic regression was performed to assess the risk of NAFLD by determining odds ratios and 95% confidence intervals (CIs). No significant differences in genotype and allele frequencies of these four SNPs were found between the NAFLD population and the controls (all P > 0.05). In addition, we did not find any association between the SREBF-1c SNPs and the clinical and biochemical parameters, such as body mass index, total cholesterol, high density lipoprotein-and low density lipoprotein-cholesterol or systolic and diastolic blood pressure, except that the rs2297508 C-allele or rs11868035 G-allele showed significant associations with lower triglyceride levels in control subjects (P < 0.01). Our findings suggested that the four polymorphisms in SREBF-1c gene are not associated with risk of NAFLD in the Chinese Han population.

Diagnostic performance of the atopy patch test with inhalant allergens.

PubMed

Fuiano, N; Diddi, G; Delvecchio, M; Incorvaia, C

2015-01-01

This study evaluated the diagnostic performance of the atopy patch test (APT) compared with skin prick testing (SPT) and in vitro IgE measurement in a large group of patients with atopic dermatitis (AD) with or without respiratory symptoms (RS). The study included 521 patients (292 males, 229 females; age, 0.5-18 years; median age, 6 years) with AD and RS with different clinical presentations: current AD, 47 patients (Group A); current AD and RS, 72 patients (Group B), past AD and RS, 69 patients (Group C); and RS only, 280 patients (Group D). Fifty-three healthy individuals served as controls. All participants underwent the APT, SPT, and CAP/RAST with the most common inhalant allergens. The presence of a control group allowed calculation of specificity and positive and negative predictive values. A significant difference was found for a positive APT versus both SPT and CAP/RAST (P < .0001) but not for SPT versus CAP/RAST. The differences for APT were significant in all group comparisons except group B vs C and group C vs D. In the control group, the APT was positive in 2% of cases (specificity of 96.2%), SPT was positive in 6% of cases (specificity of 88.4%), and CAP/RAST was positive in 4% of cases (specificity of 92.5%). In young patients sensitized to inhalant allergens with AD in addition to RS, the APT has a superior diagnostic performance to SPT and in vitro IgE measurement.

Religion, spirituality and cardiovascular disease: research, clinical implications, and opportunities in Brazil.

PubMed

Lucchese, Fernando A; Koenig, Harold G

2013-03-01

In this paper we comprehensively review published quantitative research on the relationship between religion, spirituality (R/S), and cardiovascular (CV) disease, discuss mechanisms that help explain the associations reported, examine the clinical implications of those findings, and explore future research needed in Brazil on this topic. First, we define the terms religion, spirituality, and secular humanism. Next, we review research examining the relationships between R/S and CV risk factors (smoking, alcohol/drug use, physical inactivity, poor diet, cholesterol, obesity, diabetes, blood pressure, and psychosocial stress). We then review research on R/S, cardiovascular functions (CV reactivity, heart rate variability, etc.), and inflammatory markers (IL-6, IFN-γ, CRP, fibrinogen, IL-4, IL-10). Next we examine research on R/S and coronary artery disease, hypertension, stroke, dementia, cardiac surgery outcomes, and mortality (CV mortality in particular). We then discuss mechanisms that help explain these relationships (focusing on psychological, social, and behavioral pathways) and present a theoretical causal model based on a Western religious perspective. Next we discuss the clinical applications of the research, and make practical suggestions on how cardiologists and cardiac surgeons can sensitively and sensibly address spiritual issues in clinical practice. Finally, we explore opportunities for future research. No research on R/S and cardiovascular disease has yet been published from Brazil, despite the tremendous interest and involvement of the population in R/S, making this an area of almost unlimited possibilities for researchers in Brazil.

Retinal sensitivity in subjects with type 2 diabetes mellitus: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS II, Report No. 4).

PubMed

Gella, Laxmi; Raman, Rajiv; Kulothungan, Vaitheeswaran; Saumya Pal, Swakshyar; Ganesan, Suganeswari; Sharma, Tarun

2016-06-01

To evaluate retinal sensitivity (RS) in subjects with diabetes in a population-based study and to elucidate associated risk factors for abnormal RS. A subset of 357 subjects from Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study-II was included in this study. All subjects underwent detailed ophthalmic evaluation including microperimetry and spectral domain optical coherence tomography. The prevalence of abnormal mean retinal sensitivity (MRS) was 89.1%. MRS was significantly reduced in subjects with diabetes but no retinopathy when compared with non-diabetic subjects. MRS was reduced in moderate non-proliferative diabetic retinopathy (DR) and macular oedema (ME) at 8° (p=0.04, p=0.01, respectively) and in ME at 10° (p=0.009) and 12° (p=0.036) compared with no DR. Significant negative correlation was found between MRS and best corrected visual acuity, duration of diabetes, glycosylated haemoglobin and central foveal thickness. Increased retinal thickness remained a significant risk factor (OR, 1.02; p=0.044) for abnormal MRS. Altered inner retinal layers and foveal contour were associated with reduced MRS among subjects with DR and presence of epiretinal membrane, altered foveal contour and altered retinal pigment epithelium were associated with reduced MRS. Reduced RS in those subjects with diabetes but no retinopathy suggests the early neuronal damage in type 2 diabetes mellitus. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Relationship Between ABCB1 Polymorphisms and Cold Pain Sensitivity Among Healthy Opioid-naive Malay Males.

PubMed

Zahari, Zalina; Lee, Chee Siong; Ibrahim, Muslih Abdulkarim; Musa, Nurfadhlina; Mohd Yasin, Mohd Azhar; Lee, Yeong Yeh; Tan, Soo Choon; Mohamad, Nasir; Ismail, Rusli

2017-09-01

Endogenous and exogenous opioids are substrates of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Genetic polymorphisms of ABCB1 may contribute to interindividual differences in pain modulation and analgesic responses. We investigated the relationship between ABCB1 polymorphisms and cold pain sensitivity among healthy males. Cold pain responses, including pain threshold and pain tolerance, were measured using the cold-pressor test (CPT). DNA was extracted from whole blood and genotyped for ABCB1 polymorphisms, including c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), using the allelic discrimination real-time polymerase chain reaction. A total of 152 participants were recruited in this observational study. Frequencies of mutated allele for c.1236C>T, c.2677G>T/A, and c.3435C>T polymorphisms were 56.6%, 49.7%, and 43.4%, respectively. Our results revealed an association of the CGC/CGC diplotype (c.1236C>T, c.2677G>T/A, and c.3435C>T) with cold pain sensitivity. Participants with the CGC/CGC diplotype had 90% and 72% higher cold pain thresholds (87.62 seconds vs. 46.19 seconds, P = 0.010) and cold pain tolerances (97.24 seconds vs. 56.54 seconds, P = 0.021), respectively, when compared with those without the diplotype. The CGC/CGC diplotype of ABCB1 polymorphisms was associated with variability in cold pain threshold and pain tolerance in healthy males. © 2016 World Institute of Pain.

Spanish validation of the adult Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS): relevance of clinical subtypes.

PubMed

Richarte, Vanesa; Corrales, Montserrat; Pozuelo, Marian; Serra-Pla, Juanfran; Ibáñez, Pol; Calvo, Eva; Corominas, Margarida; Bosch, Rosa; Casas, Miquel; Ramos-Quiroga, Josep Antoni

Adult attention deficit hyperactivity disorder (ADHD) has a prevalence between 2.5% and 4% of the general adult population. Over the past few decades, self-report measures have been developed for the current evaluation of adult ADHD. The ADHD-RS is a 18-items scale self-report version for assessing symptoms for ADHD DSM-IV. A validation of Spanish version of the ADHD-RS was performed. The sample consisted of 304 adult with ADHD and 94 controls. A case control study was carried out (adult ADHD vs. non ADHD). The diagnosis of ADHD was evaluated with the Structured Clinical Interview for DSM-IV (SCID-I) and the Conners Adult ADHD Diagnostic Interview for DSM-IV (CAADID-II). To determinate the internal validity of the two dimensions structure of ADHD-RS an exploratory factor analysis was performed. The α-coefficients were taken as a measure of the internal consistency of the dimensions considered. A logistic regression study was carried out to evaluate the model in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV). Average age was 33.29 (SD=10.50) and 66% of subjects were men (there were no significant differences between the two groups). Factor analysis was done with a principal component analysis followed by a normalized varimax rotation. The Kaiser-Meyer-Olkin measure of sampling adequacy tests was .868 (remarkable) and the Bartlett's test of sphericity was 2 (153)=1,835.76, P<.0005, indicating the appropriateness of the factor analysis. This two-factor model accounted for 37.81% of the explained variance. The α-coefficient of the two factors was .84 and .82. The original strategy proposed 24 point for cut-off: sensitivity (81.9%), specificity (74.7%), PPV (50.0%), NPV (93.0%), kappa coefficient .78 and area under the curve (AUC) .89. The new score strategy proposed by our group suggests different cut-off for different clinical presentations. The 24 point is the best cut-off for ADHD combined presentation: sensitivity (81.9%), specificity (87.3%), PPV (78.6%), NPV (89.4%), kappa coefficient .88 and AUC .94, and 21 point is the best cut-off for ADHD predominantly inattentive presentation: sensitivity (70.2%), specificity (76.1%), PPV (71.7%), NPV (74.8%), kappa coefficient .88 and AUC .94. In this study, the Spanish version of the ADHD-RS is a valid scale to discriminate between ADHD adults and controls. The new proposed score strategy suggests the relevance of clinical presentations in the different cut-offs selected. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

The predictive value of IL28B rs12979860, rs11881222 and rs8099917 polymorphisms and IP-10 in the therapeutic response of Egyptian genotype 4 patients.

PubMed

Derbala, Moutaz; Rizk, Nasser M; Al-Kaabi, Saad; John, Anil; Sharma, Manik; El-dweik, Nazeeh; Yakoob, Rafie; Pasic, Fuad; Almohanadi, Muneera; Alejji, Khalid; Abdelmola, Abdulatif; Butt, Mohamed

2013-09-01

Interleukin-28B (IL28B) polymorphisms have previously been reported to be strongly associated with spontaneous and treatment-induced HCV viral clearance. To assess the impact of four different IL28B polymorphisms and their haplotype combination and interferon-c inducible protein 10 (IP-10) in response to treatment in Egyptian genotype 4 patients. 159 HCV-genotype 4 patients were included. All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk. The following polymorphisms rs12979860, rs11881222, rs8103142 and rs8099917 and rs80803142 of Il-28 were known to be associated with the sustained virological response. They were genotyped using the TaqMan assay. IP-10 was assessed by Eliza. The data indicated that all SNPs are within the Hardy-Weinberg Equilibrium (HWE) except for rs8103142 (p=6.255(-9)), therefore it was excluded from the study since it deviates from HWE-P. The CC, AA and TT genotypes of rs12979860, rs11881222 and rs8099917 were the more frequent genotypes among the responders at RVR, EVR, ETR and SVR, respectively. The frequency of CC, CT, and TT genotype was 46.4%, 38.1% and 15.5% among responders of RVR, and was 46.9%, 45.9% and 7.2 among responders of SVR for rs12979860, respectively. The relapse rate was 18.0% and 16.0 % during EVR and ETR, while the response rate was 52.8%, 58.5%, 59.7% and 61.6% after 4, 12, 48 and 72 weeks of treatment. The transient virological response (TVR) was 6.9% among HCV patients. The results showed that the odds ratio and 95% CI of HCV genotype 4 patients to have a better sustained response to treatment (SVR) was 2.92, (1.83-4.68, p=2.01(-5)), 2.89 (1.79-4.70, p=2.53(-5)), and 2.73 (0.21-0.65, p=0.0007) for those with the major allele "C" of rs12979860, the "A" allele of rs11881222, and the "T" allele of rs8099917, respectively. Furthermore, the positive predictive value (PPV) of the major homozygous alleles for SVR with better response to therapy was in the following order: 78.69%, 68.42%, and 32.14% with a positive likelihood ratio of 1.95, 1.25, and 0.86 for rs12979860, rs11881222 and rs8099917, respectively. The haplotype formed between the 3 studied SNPs (rs12979860, rs11881222 and rs8099917) showed that two haplotypes (TGG and TGT) increased the probability of a poor response to therapy, but the CAT haplotype had the opposite effect. Multinomial logistic regression analysis revealed that the viral load and rs12979860 are the only significant actors involved in the efficacy of the treatment response among the cohort study. In addition, patients with SVR had significantly lower values of IP-10 than non-responder patients (NR), with a P-value<=0.001. In genotype 4 cases, the IL28B SNPs rs12979860 rs8099917, and rs11881222 are the strongest predictors of a response, while IP-10 is a strong negative biomarker of a response. Accounting for this factor is important in the individualization of treatment and enhances the degree of predictiveness of the IL28 polymorphism in the final treatment outcome. The frequent distribution of C, A and T alleles of IL28 polymorphism are higher among TVR, which may reflect sensitivity to prolonged course. Copyright © 2013. Published by Elsevier Inc.

Response to phytohaemagglutinin of lymphocytes from mice treated with anti-lymphocyte globulin

PubMed Central

Tursi, A.; Greaves, M. F.; Torrigiani, G.; Playfair, J. H. L.; Roitt, I. M.

1969-01-01

Thymus, spleen, lymph node and peripheral blood lymphocytes taken from mice treated with anti-lymphocyte globulin (ALG) showed a greatly diminished response to PHA in vitro. Recovery of circulating lymphocyte levels preceded recovery of responsiveness to PHA. The latter could be prevented by reinjection of ALG or by thymectomy. Grafts were rejected within a period equal to the normal rejection time after PHA responsiveness had recovered to a value of approximately 20 per cent of the normal. Thus the effect of ALG on thymus dependent lymphocytes in mice can be monitored by assessing the PHA sensitivity of peripheral white blood cells. ImagesFIG. 1 PMID:4900922

Fast synaptic transmission mediated by α-bungarotoxin-sensitive nicotinic acetylcholine receptors in lamina X neurones of neonatal rat spinal cord

PubMed Central

Bradaïa, A; Trouslard, J

2002-01-01

Using patch clamp recordings on neonatal rat spinal cord slices, we have looked for the presence of α-bungarotoxin-sensitive nicotinic ACh receptors (nAChRs) on sympathetic preganglionic neurones (SPNs) surrounding the central canal of the spinal cord (lamina X) and examined whether they were implicated in a fast cholinergic synaptic transmission. SPNs were identified either by their morphology using biocytin in the recording electrode and/or by antidromic stimulation of the ventral rootlets. The selective α7-containing nAChR (α7*nAChR) agonist choline (10 mm) induced a fast, rapidly desensitizing inward current, which was fully blocked by α-bungarotoxin (α-BgT; 50 nm) and strychnine (1 μm), two antagonists of α7*nAChRs. The I-V relationship of the choline-induced current showed a strong inward-going rectification. Electrically evoked excitatory postsynaptic currents (eEPSCs) could be recorded. At -60 mV, eEPSCs peaked at -26.2 pA and decayed monoexponentially with a mean time constant of 8.5 ms. The current-voltage relationship for eEPSCs exhibited a strong inward rectification and a reversal potential close to 0 mV, compatible with a non-selective cationic current. The appearance of eEPSCs was entirely suppressed by the application of 100 μm ACh or nicotine. Choline (10 mm) and 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP; 100 μm) both reduced the amplitude of eEPSCs, whereas cytisine (100 μm) had no effect. Strychnine (1 μm) and α-BgT (50 nm) both suppressed the eEPSCs. Blocking the P2X purinergic and 5-HT3 receptors had no effect on eEPSCs. DMPP induced four types of current, which differed in their onset and desensitization rate. The most frequently encountered responses were insensitive to the action of strychnine and α-BgT, and were reproduced by ACh and nicotine but not by cytisine. We conclude that SPNs of the lamina X express several classes of nAChRs and in particular α-BgT-sensitive nAChRs. This is the first demonstration in a mammalian spinal cord preparation of a fast cholinergic neurotransmission in which α-BgT-sensitive nicotinic receptors are involved. PMID:12411519

The Influence of Ship Deck-Edge Lighting on Perception of Position and Movement During Helicopter Recovery

DTIC Science & Technology

2006-07-01

sensitivity to differences between stimuli. The signal detection theory (SDT; e.g., MacMillan & Creelman , 1991) approach allows examination of both...REJECTIONS. Sensitivity (d’) and response bias (c) were calculated according to the formulae below (Azzopardi & Cowey, 1997; MacMillan & Creelman , 1991...MacMillan, N.A., & Creelman , C.D. (1991). Detection Theory: A User’s Guide. Sydney: Cambridge University Press. Royden, C.S., Banks, M.S

[Evaluation of immune status of kidney transplant recipients by combined HLA-G5 and sCD30].

PubMed

JIN, Zhan-kui; TIAN, Pu-xun; XUE, Wu-jun; DING, Xiao-ming; PAN, Xiao-ming; DING, Chen-guang; JIA, Li-ning; GE, Guan-qun; HAO, Jun-jun

2010-09-28

to study the relationship between the expression of serum human leucocyte antigen-G5 (HLA-G5)/soluble CD30 (sCD30) and the function of renal graft in kidney transplant recipients and investigate the immune status of recipients with combined HLA-G5 and sCD30. from January 2002 to November 2008, a total of 66 kidney transplant recipients in our centre were selected as subjects and divided into three groups: stable function of renal graft (n = 38), acute rejection (n = 15) and chronic rejection (n = 13). The expressions of serum HLA-G5 and sCD30 were detected. There were two different immune conditions with acute/chronic allograft rejection and normal renal graft in kidney transplant recipients as evaluated by combined HLA-G5 and sCD30. The sensitivity, specificity and critical value of the method were analyzed by the curve of receiver operating characteristic. the levels of HLA-G5 and sCD30 were significantly correlated with serum creatinine (r = -0.493, 0.691, both P < 0.01). Within the first year post-transplantation, the sensitivity was 78.6% and the specificity 85.7% when HLA-G5 critical value 82 microg/L and sCD30 critical value 12.2 microg/L. After one year post-transplantation: the sensitivity was 92.3% and the specificity 84.6% when HLA-G5 critical value 141 microg/L and sCD30 critical value 10.3 microg/L. the immune state of recipients are evaluated by combine HLA-G5 and sCD30 which may be a simple and valid method.

ηηDiazepam-induced loss of inhibitory synapses mediated by PLCδ/ Ca 2+ /calcineurin signalling downstream of GABAA receptors.

PubMed

Nicholson, Martin W; Sweeney, Aaron; Pekle, Eva; Alam, Sabina; Ali, Afia B; Duchen, Michael; Jovanovic, Jasmina N

2018-06-14

Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABA A Rs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effects of benzodiazepines in patients. However, extended benzodiazepine treatments lead to development of tolerance, a process which, despite its important therapeutic implications, remains poorly characterised. Here we report that prolonged exposure to diazepam, the most widely used benzodiazepine in clinic, leads to a gradual disruption of neuronal inhibitory GABAergic synapses. The loss of synapses and the preceding, time- and dose-dependent decrease in surface levels of GABA A Rs, mediated by dynamin-dependent internalisation, were blocked by Ro 15-1788, a competitive benzodiazepine antagonist, and bicuculline, a competitive GABA antagonist, indicating that prolonged enhancement of GABA A R activity by diazepam is integral to the underlying molecular mechanism. Characterisation of this mechanism has revealed a metabotropic-type signalling downstream of GABA A Rs, involving mobilisation of Ca 2+ from the intracellular stores and activation of the Ca 2+ /calmodulin-dependent phosphatase calcineurin, which, in turn, dephosphorylates GABA A Rs and promotes their endocytosis, leading to disassembly of inhibitory synapses. Furthermore, functional coupling between GABA A Rs and Ca 2+ stores was sensitive to phospholipase C (PLC) inhibition by U73122, and regulated by PLCδ, a PLC isoform found in direct association with GABA A Rs. Thus, a PLCδ/Ca 2+ /calcineurin signalling cascade converts the initial enhancement of GABA A Rs by benzodiazepines to a long-term downregulation of GABAergic synapses, this potentially underpinning the development of pharmacological and behavioural tolerance to these widely prescribed drugs.

Ethanol Is a Fast Channel Inhibitor of P2X4 Receptors

PubMed Central

Ostrovskaya, Olga; Asatryan, Liana; Wyatt, Letisha; Popova, Maya; Li, Kaixun; Peoples, Robert W.; Alkana, Ronald L.

2011-01-01

P2X receptors (P2XRs) are ion channels gated by synaptically released ATP. The P2X4 is the most abundant P2XR subtype expressed in the central nervous system and to date is the most ethanol-sensitive. In addition, genomic findings suggest that P2X4Rs may play a role in alcohol intake/preference. However, little is known regarding how ethanol causes the inhibition of ATP-gated currents in P2X4Rs. We begin to address this issue by investigating the effects of ethanol in wild-type and mutant D331A and M336A P2X4Rs expressed in human embryonic kidney (HEK) 293 cells using whole-cell patch-clamp methods. The results suggest that residues D331 and M336 play a role in P2X4R gating and ethanol inhibits channel functioning via a mechanism different from that in other P2XRs. Key findings from the study include: 1) ethanol inhibits ATP-gated currents in a rapid manner; 2) ethanol inhibition of ATP-gated currents does not depend on voltage and ATP concentration; 3) residues 331 and 336 slow P2X4 current deactivation and regulate the inhibitory effects of ethanol; and 4) ethanol effects are similar in HEK293 cells transfected with P2X4Rs and cultured rat hippocampal neurons transduced with P2X4Rs using a recombinant lentiviral system. Overall, these findings provide key information regarding the mechanism of ethanol action on ATP-gated currents in P2X4Rs and provide new insights into the biophysical properties of P2X4Rs. PMID:21212160

Mutation of a Zinc-Binding Residue in the Glycine Receptor α1 Subunit Changes Ethanol Sensitivity In Vitro and Alcohol Consumption In Vivo

PubMed Central

McCracken, Lindsay M.; Blednov, Yuri A.; Trudell, James R.; Benavidez, Jillian M.; Betz, Heinrich

2013-01-01

Ethanol is a widely used drug, yet an understanding of its sites and mechanisms of action remains incomplete. Among the protein targets of ethanol are glycine receptors (GlyRs), which are potentiated by millimolar concentrations of ethanol. In addition, zinc ions also modulate GlyR function, and recent evidence suggests that physiologic concentrations of zinc enhance ethanol potentiation of GlyRs. Here, we first built a homology model of a zinc-bound GlyR using the D80 position as a coordination site for a zinc ion. Next, we investigated in vitro the effects of zinc on ethanol action at recombinant wild-type (WT) and mutant α1 GlyRs containing the D80A substitution, which eliminates zinc potentiation. At D80A GlyRs, the effects of 50 and 200 mM ethanol were reduced as compared with WT receptors. Also, in contrast to what was seen with WT GlyRs, neither adding nor chelating zinc changed the magnitude of ethanol enhancement of mutant D80A receptors. Next, we evaluated the in vivo effects of the D80A substitution by using heterozygous Glra1(D80A) knock-in (KI) mice. The KI mice showed decreased ethanol consumption and preference, and they displayed increased startle responses compared with their WT littermates. Other behavioral tests, including ethanol-induced motor incoordination and strychnine-induced convulsions, revealed no differences between the KI and WT mice. Together, our findings indicate that zinc is critical in determining the effects of ethanol at GlyRs and suggest that zinc binding at the D80 position may be important for mediating some of the behavioral effects of ethanol action at GlyRs. PMID:23230213

Response of Soil Respiration to Soil Temperature and Moisture in a 50-Year-Old Oriental Arborvitae Plantation in China

PubMed Central

Yu, Xinxiao; Zha, Tianshan; Pang, Zhuo; Wu, Bin; Wang, Xiaoping; Chen, Guopeng; Li, Chunping; Cao, Jixin; Jia, Guodong; Li, Xizhi; Wu, Hailong

2011-01-01

China possesses large areas of plantation forests which take up great quantities of carbon. However, studies on soil respiration in these plantation forests are rather scarce and their soil carbon flux remains an uncertainty. In this study, we used an automatic chamber system to measure soil surface flux of a 50-year-old mature plantation of Platycladus orientalis at Jiufeng Mountain, Beijing, China. Mean daily soil respiration rates (Rs) ranged from 0.09 to 4.87 µmol CO2 m−2s−1, with the highest values observed in August and the lowest in the winter months. A logistic model gave the best fit to the relationship between hourly Rs and soil temperature (Ts), explaining 82% of the variation in Rs over the annual cycle. The annual total of soil respiration estimated from the logistic model was 645±5 g C m−2 year−1. The performance of the logistic model was poorest during periods of high soil temperature or low soil volumetric water content (VWC), which limits the model's ability to predict the seasonal dynamics of Rs. The logistic model will potentially overestimate Rs at high Ts and low VWC. Seasonally, Rs increased significantly and linearly with increasing VWC in May and July, in which VWC was low. In the months from August to November, inclusive, in which VWC was not limiting, Rs showed a positively exponential relationship with Ts. The seasonal sensitivity of soil respiration to Ts (Q10) ranged from 0.76 in May to 4.38 in October. It was suggested that soil temperature was the main determinant of soil respiration when soil water was not limiting. PMID:22163012

Effect of Preload Alterations on Left Ventricular Systolic Parameters Including Speckle-Tracking Echocardiography Radial Strain During General Anesthesia.

PubMed

Weber, Ulrike; Base, Eva; Ristl, Robin; Mora, Bruno

2015-08-01

Frequently used parameters for evaluation of left ventricular systolic function are load-sensitive. However, the impact of preload alterations on speckle-tracking echocardiographic parameters during anesthesia has not been validated. Therefore, two-dimensional (2D) speckle-tracking echocardiography radial strain (RS) was assessed during general anesthesia, simulating 3 different preload conditions. Single-center prospective observational study. University hospital. Thirty-three patients with normal left ventricular systolic function undergoing major surgery. Transgastric views of the midpapillary level of the left ventricle were acquired at 3 different positions. Fractional shortening (FS), fractional area change (FAC), and 2D speckle-tracking echocardiography RS were analyzed in the transgastric midpapillary view. Considerable correlation above 0.5 was found for FAC and FS in the zero and Trendelenburg positions (r = 0.629, r = 0.587), and for RS and FAC in the anti-Trendelenburg position (r = 0.518). In the repeated-measures analysis, significant differences among the values measured at the 3 positions were found for FAC and FS. For FAC, there were differences up to 2.8 percentage points between the anti-Trendelenburg position and the other 2 positions. For FS, only the difference between position zero and anti-Trendelenburg was significant, with an observed change of 1.66. Two-dimensional RS was not significantly different at all positions, with observed changes below 1 percentage point. Alterations in preload did not result in clinically relevant changes of RS, FS, or FAC. Observed changes for RS were smallest; however, the variation of RS was larger than that of FS or FAC. Copyright © 2015 Elsevier Inc. All rights reserved.

Seasonal and annual changes in soil respiration in relation to soil temperature, water potential and trenching.

PubMed

Lavigne, M B; Foster, R J; Goodine, G

2004-04-01

Soil respiration (rs), soil temperature (Ts) and volumetric soil water content were measured in a balsam fir (Abies balsamea (L.) Mill.) ecosystem from 1998 to 2001. Seasonal variation in root and microbial respiration, and covariation in abiotic factors confounded interpretation of the effects of Ts and soil water potential (Psis) on rs. To minimize the confounding effect of temperature, we analyzed the effect of Psis on rs during the summers of 1998-2000 when changes in Ts were slight. Soil respiration declined 25-50% in response to modest water stress (minimum Psis of -0.6 to -0.2 MPa), and between years, there was substantial variation in the relationship between rs and Psis. In the summer of 2000, 2-m2 plots were subjected to drought for 1 month and other plots were irrigated. The relationship between summertime rs and Psis in the experimental plots was similar to that estimated from the survey data obtained during the same summer. In late spring and early autumn of 2001, 2-m2 trenched and untrenched plots were subjected to drought or exposed to rainfall. It was dry in the early autumn and there was severe soil drying (Psis of -10 MPa in untrenched plots and -2 MPa in trenched plots). In spring, rs in untrenched plots responded more to modest water stress than rs in trenched plots, indicating that root respiration is more sensitive than microbial respiration to water stress at this time of year. The response to abiotic factors differed significantly between spring and autumn in untrenched plots but not in trenched plots, indicating that root activity was greater in early autumn than in late spring, and that roots acclimated to the sustained, severe water stress experienced before and during the autumn.

Alpha7 nicotinic acetylcholine receptors targeted by cholinergic developmental neurotoxicants: nicotine and chlorpyrifos.

PubMed

Slotkin, Theodore A; Southard, Matthew C; Adam, Stacey J; Cousins, Mandy M; Seidler, Frederic J

2004-09-30

Alpha7 nicotinic acetylcholine receptors (nAChRs) play a role in axonogenesis, synaptogenesis and synaptic plasticity, and are therefore potential targets for developmental neurotoxicants. We administered nicotine to neonatal rats during discrete periods spanning the onset and peak of axonogenesis/synaptogenesis, focusing on three brain regions with disparate distributions of cell bodies and neural projections: brainstem, forebrain and cerebellum. Nicotine treatment on postnatal days (PN) 1-4 had little or no effect on alpha7 nAChRs but treatment during the second (PN11-14) or third (PN21-24) weeks elicited significant decrements in receptor expression in brainstem and cerebellum, regions containing cell bodies that project to the forebrain. Exposure to chlorpyrifos, a neurotoxicant pesticide that acts partially through cholinergic mechanisms, also elicited deficits in alpha7 nAChRs during the second postnatal week but not the first week. For both nicotine and chlorpyrifos, the effects on alpha7 nAChRs were distinct from those on the alpha4beta2 subtype. Continuous prenatal nicotine exposure, which elicits subsequent, postnatal deficits in axonogenesis and synaptogenesis, also produced delayed-onset changes in alpha7 nAChRs, characterized by reductions in the forebrain and upregulation in the brainstem and cerebellum, a pattern consistent with impaired axonogenesis/synaptogenesis and reactive sprouting. Males were more sensitive to the persistent effects of prenatal nicotine exposure on alpha7 nAChRs, a pattern that mimics neurobehavioral deficits resulting from this treatment. The present findings reinforce the mechanistic involvement of alpha7 nAChRs in the actions of developmental neurotoxicants, and its biomarker potential for neuroteratogens that target neuritic outgrowth.

Atypical depression among psychiatric inpatients: clinical features and personality traits.

PubMed

Derecho, C N; Wetzler, S; McGinn, L K; Sanderson, W C; Asnis, G M

1996-06-20

This study investigates the frequency and characteristics of Atypical Depression (AD) among depressed inpatients. Twenty-one depressed inpatients received DSM-IV diagnoses, were rated on the Hamilton Depression Rating Scale (HAMD), and assessed for AD using the Atypical Depressive Disorder Scale. AD was defined as the presence of mood reactivity and two of four associated features: hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. Mood reactivity was defined as the ability to reach 50% of a non-depressed mood. All subjects completed the SCL-90, MCMI-II, and a suicide survey. Seven patients (33%) met criteria for AD. AD and non-AD patients did not differ in terms of severity of depression, history of suicide attempts, levels of clinical symptomatology, age of onset of depression, prior hospitalizations, and most personality characteristics. However, AD patients scored significantly higher than non-AD patients on the SCL-90 Interpersonal Sensitivity and MCMI-II Avoidant scales, and were more likely to be single. AD is fairly prevalent on an inpatient service, comparable to the frequency found in outpatient settings. AD is not a milder form of depression. The only differences between AD and non-AD patients reflect the personality trait of rejection sensitivity which is a defining feature of AD.

Radiosondes Corrected for Inaccuracy in RH Measurements

DOE Data Explorer

Miloshevich, Larry

2008-01-15

Corrections for inaccuracy in Vaisala radiosonde RH measurements have been applied to ARM SGP radiosonde soundings. The magnitude of the corrections can vary considerably between soundings. The radiosonde measurement accuracy, and therefore the correction magnitude, is a function of atmospheric conditions, mainly T, RH, and dRH/dt (humidity gradient). The corrections are also very sensitive to the RH sensor type, and there are 3 Vaisala sensor types represented in this dataset (RS80-H, RS90, and RS92). Depending on the sensor type and the radiosonde production date, one or more of the following three corrections were applied to the RH data: Temperature-Dependence correction (TD), Contamination-Dry Bias correction (C), Time Lag correction (TL). The estimated absolute accuracy of NIGHTTIME corrected and uncorrected Vaisala RH measurements, as determined by comparison to simultaneous reference-quality measurements from Holger Voemel's (CU/CIRES) cryogenic frostpoint hygrometer (CFH), is given by Miloshevich et al. (2006).

Association of calcium sensing receptor polymorphisms at rs1801725 with circulating calcium in breast cancer patients.

PubMed

Wang, Li; Widatalla, Sarrah E; Whalen, Diva S; Ochieng, Josiah; Sakwe, Amos M

2017-08-02

Breast cancer (BC) patients with late-stage and/or rapidly growing tumors are prone to develop high serum calcium levels which have been shown to be associated with larger and aggressive breast tumors in post and premenopausal women respectively. Given the pivotal role of the calcium sensing receptor (CaSR) in calcium homeostasis, we evaluated whether polymorphisms of the CASR gene at rs1801725 and rs1801726 SNPs in exon 7, are associated with circulating calcium levels in African American and Caucasian control subjects and BC cases. In this retrospective case-control study, we assessed the mean circulating calcium levels, the distribution of two inactivating CaSR SNPs at rs1801725 and rs1801726 in 199 cases and 384 age-matched controls, and used multivariable regression analysis to determine whether these SNPs are associated with circulating calcium in control subjects and BC cases. We found that the mean circulating calcium levels in African American subjects were higher than those in Caucasian subjects (p < 0.001). As expected, the mean calcium levels were higher in BC cases compared to control subjects (p < 0.001), but the calcium levels in BC patients were independent of race. We also show that in BC cases and control subjects, the major alleles at rs1801725 (G/T, A986S) and at rs1801726 (C/G, Q1011E) were common among Caucasians and African Americans respectively. Compared to the wild type alleles, polymorphisms at the rs1801725 SNP were associated with higher calcium levels (p = 0.006) while those at rs1801726 were not. Using multivariable linear mixed-effects models and adjusting for age and race, we show that circulating calcium levels in BC cases were associated with tumor grade (p = 0.009), clinical stage (p = 0.003) and more importantly, with inactivating mutations of the CASR at the rs1801725 SNP (p = 0.038). These data suggest that decreased sensitivity of the CaSR to calcium due to inactivating polymorphisms at rs1801725, may predispose up to 20% of BC cases to high circulating calcium-associated larger and/or aggressive breast tumors.

αConotoxin ArIB[V11L,V16D] is a potent and selective antagonist at rat and human native α7 nicotinic acetylcholine receptors

PubMed Central

Innocent, Neal; Livingstone, Phil D.; Hone, Arik; Kimura, Atsuko; Young, Tracey; Whiteaker, Paul; McIntosh, J. Michael; Wonnacott, Susan

2008-01-01

A recently developed α-conotoxin, α-CtxArIB[V11L,V16D] is a potent and selective competitive antagonist at rat recombinant α7 nicotinic acetylcholine receptors (nAChRs), making it an attractive probe for this receptor subtype. α7 nAChRs are potential therapeutic targets that are widely expressed in both neuronal and non-neuronal tissues where they are implicated in a variety of functions. Here we evaluate this toxin at rat and human native nAChRs. Functional α7 nAChR responses were evoked by choline plus the allosteric potentiator PNU-120596 in rat PC12 cells and human SHSY5Y cells loaded with calcium indicators. α-CtxArIB[V11L,V16D] specifically inhibited α7 nAChR-mediated increases in Ca2+ in PC12 cells. Responses to other stimuli (5-iodo-A-85380, nicotine or KCl) that did not activate α7 nAChRs were unaffected. Human α7 nAChRs were also sensitive to α-CtxArIB[V11L,V16D]: ACh-evoked currents in X. laevis oocytes expressing human α7 nAChRs were inhibited by α-CtxArIB[V11L,V16D] (IC50 3.4 nM) in a slowly reversible manner, with full recovery taking 15 min. This is consistent with the timecourse of recovery from blockade of rat α7 nAChRs in PC12 cells. α-CtxArIB[V11L,V16D] inhibited human native α7 nAChRs in SHSY5Y cells, activated by either choline or AR-R17779 plus PNU-120596. Rat brain α7 nAChRs contribute to dopamine release from striatal minces: α-CtxArIB[V11L,V16D] (300 nM) selectively inhibited choline-evoked dopamine release without affecting responses evoked by nicotine that activates heteromeric nAChRs. This study establishes that α-CtxArIB[V11L,V16D] selectively inhibits human and rat native α7 nAChRs with comparable potency, making this a potentially useful antagonist for investigating α7 nAChR functions. PMID:18664588

Prenatal Stress Exposure, Oxytocin Receptor Gene (OXTR) Methylation and Child Autistic Traits: The Moderating Role of OXTR rs53576 Genotype

PubMed Central

Rijlaarsdam, Jolien; van IJzendoorn, Marinus H.; Verhulst, Frank C; Jaddoe, Vincent W. V.; Felix, Janine F.; Tiemeier, Henning; Bakermans-Kranenburg, Marian J.

2017-01-01

Lay Abstract The gene encoding the oxytocin receptor (OXTR), localized on chromosome 3p25, is considered a promising candidate for explaining genetic vulnerability to autistic traits. Although several lines of evidence implicate OXTR SNP rs53576 (G/A) variation in social behavior, findings have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. This study investigated the main and interactive effects of OXTR rs53576 genotype, stress exposure, and OXTR methylation on child autistic traits. Prenatal maternal stress exposure, but not OXTR rs53576 genotype and OXTR methylation, showed a main effect on child autistic traits. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction. More specifically, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G-allele homozygous children but not for A-allele carriers. These results highlight the importance of incorporating epi-allelic information and support the role of OXTR methylation in child autistic traits. Scientific Abstract Findings of studies investigating OXTR SNP rs53576 (G-A) variation in social behavior have been inconsistent, possibly because DNA methylation after stress exposure was eliminated from consideration. Our goal was to examine OXTR rs53576 allele-specific sensitivity for neonatal OXTR DNA methylation in relation to (1) a prenatal maternal stress composite, and (2) child autistic traits. Prospective data from fetal life to age 6 years were collected in a total of 743 children participating in the Generation R Study. Prenatal maternal stress exposure was uniquely associated with child autistic traits but was unrelated to OXTR methylation across both OXTR rs53576 G-allele homozygous children and A-allele carriers. For child autistic traits in general and social communication problems in particular, we observed a significant OXTR rs53576 genotype by OXTR methylation interaction in the absence of main effects, suggesting that opposing effects cancelled each other out. Indeed, OXTR methylation levels were positively associated with social problems for OXTR rs53576 G-allele homozygous children but not for A-allele carriers. These results highlight the importance of incorporating epi-allelic information and support the role of OXTR methylation in child autistic traits. PMID:27520745

A SCN10A SNP biases human pain sensitivity

PubMed Central

Duan, Guangyou; Han, Chongyang; Wang, Qingli; Guo, Shanna; Zhang, Yuhao; Ying, Ying; Huang, Penghao; Zhang, Li; Macala, Lawrence; Shah, Palak; Zhang, Mi; Li, Ningbo; Dib-Hajj, Sulayman D; Zhang, Xianwei

2016-01-01

Background: Nav1.8 sodium channels, encoded by SCN10A, are preferentially expressed in nociceptive neurons and play an important role in human pain. Although rare gain-of-function variants in SCN10A have been identified in individuals with painful peripheral neuropathies, whether more common variants in SCN10A can have an effect at the channel level and at the dorsal root ganglion, neuronal level leading to a pain disorder or an altered normal pain threshold has not been determined. Results: Candidate single nucleotide polymorphism association approach together with experimental pain testing in human subjects was used to explore possible common SCN10A missense variants that might affect human pain sensitivity. We demonstrated an association between rs6795970 (G > A; p.Ala1073Val) and higher thresholds for mechanical pain in a discovery cohort (496 subjects) and confirmed it in a larger replication cohort (1005 female subjects). Functional assessments showed that although the minor allele shifts channel activation by −4.3 mV, a proexcitatory attribute, it accelerates inactivation, an antiexcitatory attribute, with the net effect being reduced repetitive firing of dorsal root ganglion neurons, consistent with lower mechanical pain sensitivity. Conclusions: At the association and mechanistic levels, the SCN10A single nucleotide polymorphism rs6795970 biases human pain sensitivity. PMID:27590072

Forest floor and mineral soil respiration rates in a northern Minnesota red pine chronosequence

USGS Publications Warehouse

Powers, Matthew; Kolka, Randall; Bradford, John B.; Palik, Brian J.; Jurgensen, Martin

2018-01-01

We measured total soil CO2 efflux (RS) and efflux from the forest floor layers (RFF) in red pine (Pinus resinosaAit.) stands of different ages to examine relationships between stand age and belowground C cycling. Soil temperature and RS were often lower in a 31-year-old stand (Y31) than in 9-year-old (Y9), 61-year-old (Y61), or 123-year-old (Y123) stands. This pattern was most apparent during warm summer months, but there were no consistent differences in RFF among different-aged stands. RFF represented an average of 4–13% of total soil respiration, and forest floor removal increased moisture content in the mineral soil. We found no evidence of an age effect on the temperature sensitivity of RS, but respiration rates in Y61 and Y123 were less sensitive to low soil moisture than RS in Y9 and Y31. Our results suggest that soil respiration’s sensitivity to soil moisture may change more over the course of stand development than its sensitivity to soil temperature in red pine, and that management activities that alter landscape-scale age distributions in red pine forests could have significant impacts on rates of soil CO2 efflux from this forest type.

RF Reference Switch for Spaceflight Radiometer Calibration

NASA Technical Reports Server (NTRS)

Knuble, Joseph

2013-01-01

The goal of this technology is to provide improved calibration and measurement sensitivity to the Soil Moisture Active Passive Mission (SMAP) radiometer. While RF switches have been used in the past to calibrate microwave radiometers, the switch used on SMAP employs several techniques uniquely tailored to the instrument requirements and passive remote-sensing in general to improve radiometer performance. Measurement error and sensitivity are improved by employing techniques to reduce thermal gradients within the device, reduce insertion loss during antenna observations, increase insertion loss temporal stability, and increase rejection of radar and RFI (radio-frequency interference) signals during calibration. The two legs of the single-pole double-throw reference switch employ three PIN diodes per leg in a parallel-shunt configuration to minimize insertion loss and increase stability while exceeding rejection requirements at 1,413 MHz. The high-speed packaged diodes are selected to minimize junction capacitance and resistance while ensuring the parallel devices have very similar I-V curves. Switch rejection is improved by adding high-impedance quarter-wave tapers before and after the diodes, along with replacing the ground via of one diode per leg with an open circuit stub. Errors due to thermal gradients in the switch are reduced by embedding the 50-ohm reference load within the switch, along with using a 0.25-in. (approximately equal to 0.6-cm) aluminum prebacked substrate. Previous spaceflight microwave radiometers did not embed the reference load and thermocouple directly within the calibration switch. In doing so, the SMAP switch reduces error caused by thermal gradients between the load and switch. Thermal issues are further reduced by moving the custom, highspeed regulated driver circuit to a physically separate PWB (printed wiring board). Regarding RF performance, previous spaceflight reference switches have not employed high-impedance tapers to improve rejection. The use of open-circuit stubs instead of a via to provide an improved RF short is unique to this design. The stubs are easily tunable to provide high rejection at specific frequencies while maintaining very low insertion loss in-band.

Proteomic signatures in plasma during early acute renal allograft rejection.

PubMed

Freue, Gabriela V Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F; Ng, Raymond T; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H; Wilson-McManus, Janet; McManus, Bruce M; Keown, Paul A; McMaster, W Robert

2010-09-01

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change >or=1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and beta(2)-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and controls throughout the period of quiescent follow-up. Results were validated using ELISA where possible, and initial cross-validation estimated a sensitivity of 80% and specificity of 90% for classification of BCAR based on a four-protein ELISA classifier. This study provides evidence that protein concentrations in plasma may provide a relevant measure for the occurrence of BCAR and offers a potential tool for immunologic monitoring.

Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection*

PubMed Central

Freue, Gabriela V. Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P.; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F.; Ng, Raymond T.; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H.; Wilson-McManus, Janet; McManus, Bruce M.; Keown, Paul A.; McMaster, W. Robert

2010-01-01

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change ≥1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and β2-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and controls throughout the period of quiescent follow-up. Results were validated using ELISA where possible, and initial cross-validation estimated a sensitivity of 80% and specificity of 90% for classification of BCAR based on a four-protein ELISA classifier. This study provides evidence that protein concentrations in plasma may provide a relevant measure for the occurrence of BCAR and offers a potential tool for immunologic monitoring. PMID:20501940

Clinical and immunological relevance of antibodies in solid organ transplantation.

PubMed

Mehra, N K; Baranwal, A K

2016-12-01

The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection. Long-term graft survival too is adversely affected by the presence of either pre- or post-transplant DSA. HLA matching status of the recipient - donor pair - is an important factor in the modulation of humoral response following transplantation and in a way affects de novo development of DSA. Data collected over the past decade clearly indicate significantly lower level of DSAs in optimally matched donor-recipient pairs. HLA mismatches especially those on HLA-DR and HLA-C loci have wider implications on post-transplant graft survival. The presence of circulating anti-HLA antibodies leads to endothelial damage in the newly grafted organ through complement dependent or independent pathways. Although detection of C4d deposition in renal biopsies serves as an important indicator of humoral rejection, its absence does not preclude the presence of DSAs and humoral rejection, and hence, it cannot be relied upon in every case. The emergence of epitope-based screening for anti-HLA antibodies on Luminex platform with high degree of sensitivity has revolutionized the screening for anti-HLA antibodies and DSAs. Studies indicate that humoral response to non-HLA antigens might also have a detrimental effect on allograft survival. High titres of such circulating antibodies may even lead to hyperacute rejection. Pre-emptive testing of solid organ recipients, especially kidney transplant recipients for anti-HLA and non-HLA antibodies and aggressive post-transplant monitoring of allograft function to detect DSAs using Luminex-based tests, is highly recommended. © 2016 John Wiley & Sons Ltd.

Alterations in GluR2 AMPA receptor phosphorylation at serine 880 following group I metabotropic glutamate receptor stimulation in the rat dorsal striatum.

PubMed

Ahn, Sung Min; Choe, Eun Sang

2010-04-01

Phosphorylation of ionotropic glutamate receptors in the brain plays a crucial role in the regulation of synaptic plasticity. In this study, we investigated the regulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor phosphorylation by the stimulation of group I metabotropic glutamate receptors (mGluRs) in the dorsal striatum in vivo. The results showed that intrastriatal infusion of the group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG, 250 nmol), enhanced the sensitivity of GluR2 subunit in its phosphorylation at serine 880 (S880) in the dorsal striatum. This enhancement of the sensitivity of GluR2-S880 phosphorylation was reduced by blocking group I mGluRs and N-methyl-D-aspartate (NMDA) receptors. Similar reduction of the enhancement was also induced by inhibiting phospholipase C (PLC), calcium/calmodulin-dependent protein kinase (CaMK), c-Jun N-terminal kinase (JNK), and protein kinase C (PKC). Inhibition of protein phosphatase (PP) 1/2A and calcineurin (PP2B) alone enhanced GluR2-S880 phosphorylation in the dorsal striatum, whereas inhibition of these phosphatases did not further enhance the S880 phosphorylation by DHPG stimulation. In addition, inhibition of PP1/2A or PP2B also enhanced the phosphorylation of CaMKII, JNK and PKC. These data suggest that the phosphorylation of AMPA receptor GluR2 subunit at S880 is subject to the upregulation by the stimulation of group I mGluRs. Interactions among glutamate receptors, protein kinases, and PPs participate in this upregulation. (c) 2009 Wiley-Liss, Inc.

A common variation of the PTEN gene is associated with peripheral insulin resistance.

PubMed

Grinder-Hansen, L; Ribel-Madsen, R; Wojtaszewski, J F P; Poulsen, P; Grunnet, L G; Vaag, A

2016-09-01

Phosphatase and tensin homologue (PTEN) reduces insulin sensitivity by inhibiting the phosphatidylinositol 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue (Akt) pathway. This study investigated how a common single nucleotide polymorphism near PTEN, previously associated with fasting levels of plasma insulin and glucose, influences in vivo glucose metabolism and insulin signalling. The primary outcome measure was the gene variant's association with peripheral glucose disposal rate and, secondarily, whether this association was explained by altered activities of PTEN targets PI3K and Akt. A total of 183 normoglycaemic Danes, including 158 twins and 25 singletons, were genotyped for PTEN rs11202614, which is in complete linkage disequilibrium with rs2142136 and rs10788575, which have also been reported in association with glycaemic traits and type 2 diabetes (T2D). Hepatic and peripheral insulin sensitivity was measured using tracer and euglycaemic-hyperinsulinaemic clamp techniques; insulin secretion was assessed by intravenous glucose tolerance test; and muscle biopsies were taken during insulin infusion from 150 twins for measurement of PI3K and Akt activities. The minor G allele of PTEN rs11202614 was associated with elevated fasting plasma insulin levels and a decreased peripheral glucose disposal rate, but not with the hepatic insulin resistance index or insulin secretion measured as the first-phase insulin response and disposition index. The single nucleotide polymorphism was not associated with either PI3K or Akt activities. A common PTEN variation is associated with peripheral insulin resistance and subsequent risk of developing T2D. However, the association with insulin resistance is not explained by decreased proximal insulin signalling in skeletal muscle. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The PNPLA3 rs738409 G-allele associates with reduced fasting serum triglyceride and serum cholesterol in Danes with impaired glucose regulation.

PubMed

Krarup, Nikolaj Thure; Grarup, Niels; Banasik, Karina; Friedrichsen, Martin; Færch, Kristine; Sandholt, Camilla Helene; Jørgensen, Torben; Poulsen, Pernille; Witte, Daniel Rinse; Vaag, Allan; Sørensen, Thorkild; Pedersen, Oluf; Hansen, Torben

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common condition, associated with hepatic insulin resistance and the metabolic syndrome including hyperglycaemia and dyslipidemia. We aimed at studying the potential impact of the NAFLD-associated PNPLA3 rs738409 G-allele on NAFLD-related metabolic traits in hyperglycaemic individuals. The rs738409 variant was genotyped in the population-based Inter99 cohort examined by an oral glucose-tolerance test, and a combined study-sample consisting of 192 twins (96 twin pairs) and a sub-set of the Inter99 population (n = 63) examined by a hyperinsulinemic euglycemic clamp (n(total) = 255). In Inter99, we analyzed associations of rs738409 with components of the WHO-defined metabolic syndrome (n = 5,847) and traits related to metabolic disease (n = 5,663). In the combined study sample we elucidated whether the rs738409 G-allele altered hepatic or peripheral insulin sensitivity. Study populations were divided into individuals with normal glucose-tolerance (NGT) and with impaired glucose regulation (IGR). The case-control study showed no associations with components of the metabolic syndrome or the metabolic syndrome. Among 1,357 IGR individuals, the rs738409 G-allele associated with decreased fasting serum triglyceride levels (per allele effect(β) = -9.9% [-14.4%;-4.0% (95% CI)], p = 5.1×10(-5)) and fasting total cholesterol (β = -0.2 mmol/l [-0.3;-0.01 mmol/l(95% CI)], p = 1.5×10(-4)). Meta-analyses showed no impact on hepatic or peripheral insulin resistance in carriers of the rs738409 G-allele. Our findings suggest that the G-allele of PNPLA3 rs738409 associates with reduced fasting levels of cholesterol and triglyceride in individuals with IGR.

Association between ErbB4 single nucleotide polymorphisms and susceptibility to schizophrenia: A meta-analysis of case-control studies.

PubMed

Feng, Yanguo; Cheng, Dejun; Zhang, Chaofeng; Li, Yuchun; Zhang, Zhiying; Wang, Juan; Feng, Xiao

2017-02-01

Accumulating studies have reported inconsistent association between ErbB4 single nucleotide polymorphisms (SNPs) and predisposition to schizophrenia. To better interpret this issue, here we conducted a meta-analysis using published case-control studies. We conducted a systematic search of MEDLINE (Pubmed), Embase (Ovid), Web of Science (Thomson-Reuters) to identify relevant references. The association between ErbB4 SNPs and schizophrenia was assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was evaluated by I squared (I) statistics and Cochran's Q test. To appraise the stability of results, we employed sensitivity analysis by omitting 1 single study each time. To assess the potential publication bias, we conducted trim and fill analysis. Seven studies published in English comprising 3162 cases and 4264 controls were included in this meta-analysis. Meta-analyses showed that rs707284 is statistically significantly associated with schizophrenia susceptibility among Asian and Caucasian populations under the allelic model (OR = 0.91, 95% CI: 0.83-0.99, P = 0.035). Additionally, a marginal association (P < 0.1) was observed between rs707284 and schizophrenia risk among Asian and Caucasian populations under the recessive (OR = 0.85, 95% CI: 0.72-1.01, P = 0.065) and homozygous (OR = 0.84, 95% CI: 0.68-1.03, P = 0.094) models. In the Asian subgroup, rs707284 was also noted to be marginally associated with schizophrenia under the recessive model (OR = 0.84, 95% CI: 0.70-1.00, P = 0.053). However, no statistically significant association was found between rs839523, rs7598440, rs3748962, and rs2371276 and schizophrenia risk. This meta-analysis suggested that rs707284 may be a potential ErbB4 SNP associated with susceptibility to schizophrenia. Nevertheless, due to the limited sample size in this meta-analysis, more large-scale association studies are still needed to confirm the results.

The supportive roles of religion and spirituality in end-of-life and palliative care of patients with cancer in a culturally diverse context: a literature review.

PubMed

López-Sierra, Héctor E; Rodríguez-Sánchez, Jesús

2015-03-01

This is a literature review of the supportive roles of religion and spirituality (R/S) in end-of-life (EoL) and palliative care of patients with cancer in a culturally diverse context. This review examines 26 noteworthy articles published between August 2013 and August 2014 from five well supported databases. Current evidence shows that R/S evokes in patients the sources to find the necessary inner strengths, which includes perspective thinking, rituals for transcending immediate physical condition and modalities of coping with their oncological illnesses. R/S are not a monolithically experience for they always manifest themselves in diverse cultural settings. As such, R/S provide the individual and their families with a practical context and social memory, which includes traditions and social family practices for maintaining meaning and well-being. Nonetheless, although various dimensions of R/S show a link between cancer risk factors and well being in cancer patients, more specific dimensions of R/S need to be studied taking into account the individuals' particular religious and cultural contexts, so that R/S variables within that context can provide a greater integrative structure for understanding and to move the field forward. Behavioral, cognitive and psychosocial scientists have taken a more in-depth look at the claims made in the past, suggesting that a relationship between R/S, cultural diversity and health exists. Case in point are the studies on EoL care, which have progressively considered the role of cultural, religion and spiritual diversity in the care of patients with oncological terminal illnesses. Beyond these facts, this review also shows that EoL supportive and palliative care providers could further enhance their practical interventions by being sensitive and supportive of cultural diversity. http://links.lww.com/COSPC/A10

RS9, a novel Nrf2 activator, attenuates light-induced death of cells of photoreceptor cells and Müller glia cells.

PubMed

Inoue, Yuki; Shimazawa, Masamitsu; Noda, Yasuhiro; Nagano, Ryota; Otsuka, Tomohiro; Kuse, Yoshiki; Nakano, Yukimichi; Tsuruma, Kazuhiro; Nakagami, Yasuhiro; Hara, Hideaki

2017-06-01

The retina is highly sensitive to oxidative stress because of its high consumption of oxygen associated with the phototransductional processes. Recent findings have suggested that oxidative stress is involved in the pathology of age-related macular degeneration, a progressive degeneration of the central retina. A well-known environmental risk factor is light exposure, as excessive and continuous light exposure can damage photoreceptors. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that controls antioxidative responses and phase 2 enzymes. Thus, we hypothesized that RS9, a specific activator of Nrf2, decreases light-induced retinal cell death in vivo and in vitro. Nrf2 was detected in the nucleus of the 661W cells exposed to RS9 and also after light exposure, and the Nrf2-antioxidant response element binding was increased in 661W cells after exposure to RS9. Consequentially, the expression of the phase 2 enzyme's mRNAs of Ho-1, Nqo-1, and Gclm genes was increased in 661W cells after exposure to RS9. Furthermore, RS9 decreased the light-induced death of 661W cells (2500 lux, 24 h), and also reduced the functional damages and the histological degeneration of the nuclei in the outer nuclear layer or the retina in the in vivo studies (8000 lux, 3 h). Heme oxygenase-1 was increased after light exposure, and Nrf2 was translocated into the nucleus after light exposure in vivo. Silencing of Ho-1 reduced the protective effects of RS9 against light-induced death of 661W cells. These findings indicate that RS9 has therapeutic potential for retinal diseases that are aggravated by light exposure. © 2017 International Society for Neurochemistry.

Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study.

PubMed

Claudio-Campos, Karla; Labastida, Aurora; Ramos, Alga; Gaedigk, Andrea; Renta-Torres, Jessicca; Padilla, Dariana; Rivera-Miranda, Giselle; Scott, Stuart A; Ruaño, Gualberto; Cadilla, Carmen L; Duconge-Soler, Jorge

2017-01-01

Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed. We also aimed at characterizing the genomic structure and admixture pattern of this study cohort. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis. The CYP2C9 variant rs2860905, which was found in all the major haplotypes occurring in the Puerto Rican population, showed stronger association with warfarin sensitivity (<4 mg/day) than common variants CYP2C9 * 2 and CYP2C9 * 3 . Although, CYP2C9 * 2 and CYP2C9 * 3 are separately contained within two of the haplotypes, 10 subjects with the sensitive phenotype were carriers of only the CYP2C9 rs2860905 variant. Other polymorphisms in CES2 and ABCB1 were found to be associated with warfarin resistance. Incorporation of rs 2860905 in a regression model ( R 2 = 0.63, MSE = 0.37) that also includes additional genetics (i.e., VKORC1 -1639 G>A; CYP2C9 rs1856908; ABCB1 c.IVS9-44A>G/ rs10276036; CES2 c.269-965A>G/ rs4783745) and non-genetic factors (i.e., hypertension, diabetes and age) showed better prediction of warfarin dose requirements than CYP2C9 * 2 and CYP2C9 * 3 combined (partial R 2 = 0.132 vs. 0.023 and 0.007, respectively, p < 0.001). The genetic background of Puerto Ricans in the study cohort showed a tri-hybrid admixture pattern, with a slightly higher than expected contribution of Native American ancestry (25%). The genomic diversity of Puerto Ricans is highlighted by the presence of four different major haplotype blocks in the CYP2C9 locus. Although, our findings need further replication, this study contributes to the field by identifying novel genetic variants that increase predictability of stable warfarin dosing among Caribbean Hispanics.

Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes

PubMed Central

Kacerovsky-Bielesz, Gertrud; Chmelik, Marek; Ling, Charlotte; Pokan, Rochus; Szendroedi, Julia; Farukuoye, Michaela; Kacerovsky, Michaela; Schmid, Albrecht I.; Gruber, Stephan; Wolzt, Michael; Moser, Ewald; Pacini, Giovanni; Smekal, Gerhard; Groop, Leif; Roden, Michael

2009-01-01

OBJECTIVE We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations with gene polymorphisms. RESEARCH DESIGN AND METHODS We studied 24 nonobese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using1H and31P magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS Relatives had slightly lower (P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% (P = 0.0001), being 23% higher (P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity (P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis (P = 0.02) and insulin sensitivity response to exercise training (P = 0.05). ATP synthase flux correlated with O2uptake and insulin sensitivity. CONCLUSIONS The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. In addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. PMID:19265027

Resistant starch lowers postprandial glucose and leptin in overweight adults consuming a moderate-to-high-fat diet: a randomized-controlled trial.

PubMed

Maziarz, Mindy Patterson; Preisendanz, Sara; Juma, Shanil; Imrhan, Victorine; Prasad, Chandan; Vijayagopal, Parakat

2017-02-21

High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption. Using a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate. At baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories). Consuming 30 g HAM-RS2 daily for 6 weeks can improve glucose homeostasis, lower leptin concentrations, and increase fasting PYY in healthy overweight adults without impacting body composition and may aid in the prevention of chronic disease. However, between-group differences in biomarkers were not observed and future research is warranted before specific recommendations can be made. None.

Projecting the health and economic impact of road safety initiatives: a case study of a multi-country project.

PubMed

Esperato, Alexo; Bishai, David; Hyder, Adnan A

2012-01-01

The Road Safety in 10 Countries (RS-10) project will implement 12 different road safety interventions at specific sites within 10 low- and middle-income countries (LMICs). This evaluation reports the number of lives that RS-10 is projected to save in those locations, the economic value of the risk reduction, and the maximum level of investment that a public health intervention of this magnitude would be able to incur before its costs outweigh its health benefits. We assumed a 5-year time implementation horizon corresponding to the duration of RS-10. Based on a preliminary literature review, we estimated the effectiveness for each of the RS-10 interventions. Applying these effectiveness estimates to the size of the population at risk at RS-10 sites, we calculated the number of lives and life years saved (LYS) by RS-10. We projected the value of a statistical life (VSL) in each RS-10 country based on gross national income (GNI) and estimated the value of the lives saved using each country's VSL. Sensitivity analysis addressed robustness to assumptions about elasticity, discount rates, and intervention effectiveness. From the evidence base reviewed, only 13 studies met our selection criteria. Such a limited base presents uncertainties about the potential impact of the modeled interventions. We tried to account for these uncertainties by allowing effectiveness to vary ± 20 percent for each intervention. Despite this variability, RS-10 remains likely to be worth the investment. RS-10 is expected to save 10,310 lives over 5 years (discounted at 3%). VSL and $/LYS methods provide concordant results. Based on our estimates of each country's VSL, the respective countries would be willing to pay $2.45 billion to lower these fatality risks (varying intervention effectiveness by ± 20 percent, the corresponding range is $2.0-$2.9 billion). Analysis based on $/LYS shows that the RS-10 project will be cost-effective as long as its costs do not exceed $5.14 billion (under ± 20% intervention effectiveness, the range = $4.1-$6.2 billion). Even at low efficacy, these estimates are still several orders of magnitude above the $125 million projected investment. RS-10 is likely to yield high returns for invested resources. The study's chief limitation was the reliance on the world's limited evidence base on how effective the road safety interventions will be. Planned evaluation of RS-10 will enhance planners' ability to conduct economic assessments of road safety in developing countries.

Correlating Resting-State Functional Magnetic Resonance Imaging Connectivity by Independent Component Analysis-Based Epileptogenic Zones with Intracranial Electroencephalogram Localized Seizure Onset Zones and Surgical Outcomes in Prospective Pediatric Intractable Epilepsy Study.

PubMed

Boerwinkle, Varina L; Mohanty, Deepankar; Foldes, Stephen T; Guffey, Danielle; Minard, Charles G; Vedantam, Aditya; Raskin, Jeffrey S; Lam, Sandi; Bond, Margaret; Mirea, Lucia; Adelson, P David; Wilfong, Angus A; Curry, Daniel J

2017-09-01

The purpose of this study was to prospectively investigate the agreement between the epileptogenic zone(s) (EZ) localization by resting-state functional magnetic resonance imaging (rs-fMRI) and the seizure onset zone(s) (SOZ) identified by intracranial electroencephalogram (ic-EEG) using novel differentiating and ranking criteria of rs-fMRI abnormal independent components (ICs) in a large consecutive heterogeneous pediatric intractable epilepsy population without an a priori alternate modality informing EZ localization or prior declaration of total SOZ number. The EZ determination criteria were developed by using independent component analysis (ICA) on rs-fMRI in an initial cohort of 350 pediatric patients evaluated for epilepsy surgery over a 3-year period. Subsequently, these rs-fMRI EZ criteria were applied prospectively to an evaluation cohort of 40 patients who underwent ic-EEG for SOZ identification. Thirty-seven of these patients had surgical resection/disconnection of the area believed to be the primary source of seizures. One-year seizure frequency rate was collected postoperatively. Among the total 40 patients evaluated, agreement between rs-fMRI EZ and ic-EEG SOZ was 90% (36/40; 95% confidence interval [CI], 0.76-0.97). Of the 37 patients who had surgical destruction of the area believed to be the primary source of seizures, 27 (73%) rs-fMRI EZ could be classified as true positives, 7 (18%) false positives, and 2 (5%) false negatives. Sensitivity of rs-fMRI EZ was 93% (95% CI 78-98%) with a positive predictive value of 79% (95% CI, 63-89%). In those with cryptogenic localization-related epilepsy, agreement between rs-fMRI EZ and ic-EEG SOZ was 89% (8/9; 95% CI, 0.52-99), with no statistically significant difference between the agreement in the cryptogenic and symptomatic localization-related epilepsy subgroups. Two children with negative ic-EEG had removal of the rs-fMRI EZ and were seizure free 1 year postoperatively. Of the 33 patients where at least 1 rs-fMRI EZ agreed with the ic-EEG SOZ, 24% had at least 1 additional rs-fMRI EZ outside the resection area. Of these patients with un-resected rs-fMRI EZ, 75% continued to have seizures 1 year later. Conversely, among 75% of patients in whom rs-fMRI agreed with ic-EEG SOZ and had no anatomically separate rs-fMRI EZ, only 24% continued to have seizures 1 year later. This relationship between extraneous rs-fMRI EZ and seizure outcome was statistically significant (p = 0.01). rs-fMRI EZ surgical destruction showed significant association with postoperative seizure outcome. The pediatric population with intractable epilepsy studied prospectively provides evidence for use of resting-state ICA ranking criteria, to identify rs-fMRI EZ, as developed by the lead author (V.L.B.). This is a high yield test in this population, because no seizure nor particular interictal epilepiform activity needs to occur during the study. Thus, rs-fMRI EZ detected by this technique are potentially informative for epilepsy surgery evaluation and planning in this population. Independent of other brain function testing modalities, such as simultaneous EEG-fMRI or electrical source imaging, contextual ranking of abnormal ICs of rs-fMRI localized EZs correlated with the gold standard of SOZ localization, ic-EEG, across the broad range of pediatric epilepsy surgery candidates, including those with cryptogenic epilepsy.

Purinergic modulation of preBötzinger complex inspiratory rhythm in rodents: the interaction between ATP and adenosine

PubMed Central

Zwicker, J D; Rajani, V; Hahn, L B; Funk, G D

2011-01-01

Abstract ATP signalling in the CNS is mediated by a three-part system comprising the actions of ATP (and ADP) at P2 receptors (P2Rs), adenosine (ADO) at P1 receptors (P1Rs), and ectonucleotidases that degrade ATP into ADO. ATP excites preBötzinger complex (preBötC) inspiratory rhythm-generating networks where its release attenuates the hypoxic depression of breathing. Its metabolite, ADO, inhibits breathing through unknown mechanisms that may involve the preBötC. Our objective is to understand the dynamics of this signalling system and its influence on preBötC networks. We show that the preBötC of mouse and rat is sensitive to P2Y1 purinoceptor (P2Y1R) activation, responding with a >2-fold increase in frequency. Remarkably, the mouse preBötC is insensitive to ATP. Only after block of A1 ADORs is the ATP-evoked, P2Y1R-mediated frequency increase observed. This demonstrates that ATP is rapidly degraded to ADO, which activates inhibitory A1Rs, counteracting the P2Y1R-mediated excitation. ADO sensitivity of mouse preBötC was confirmed by a frequency decrease that was absent in rat. Differential ectonucleotidase activities are likely to contribute to the negligible ATP sensitivity of mouse preBötC. Real-time PCR analysis of ectonucleotidase isoforms in preBötC punches revealed TNAP (degrades ATP to ADO) or ENTPDase2 (favours production of excitatory ADP) as the primary constituent in mouse and rat, respectively. These data further establish the sensitivity of this vital network to P2Y1R-mediated excitation, emphasizing that individual components of the three-part signalling system dramatically alter network responses to ATP. Data also suggest therapeutic potential may derive from methods that alter the ATP–ADO balance to favour the excitatory actions of ATP. PMID:21788352

Use of [18F]FDG PET to Monitor The Development of Cardiac Allograft Rejection

PubMed Central

Daly, Kevin P.; Dearling, Jason L. J.; Seto, Tatsuichiro; Dunning, Patricia; Fahey, Frederic; Packard, Alan B.; Briscoe, David M.

2014-01-01

Background Positron Emission Tomography (PET) has the potential to be a specific, sensitive and quantitative diagnostic test for transplant rejection. To test this hypothesis, we evaluated 18F-labeled fluorodeoxyglucose ([18F]FDG) and 13N-labeled ammonia ([13N]NH3) small animal PET imaging in a well-established murine cardiac rejection model. Methods Heterotopic transplants were performed using minor MHC mismatched B6.C-H2bm12 donor hearts in C57BL/6(H-2b) recipients. C57BL/6 donor hearts into C57BL/6 recipients served as isograft controls. [18F]FDG PET imaging was performed weekly between post-transplant days 7 and 42 and the percent injected dose was computed for each graft. [13N]NH3 imaging was performed to evaluate myocardial perfusion. Results There was a significant increase in [18F]FDG uptake in allografts from day 14 to day 21 (1.6% to 5.2%; P<0.001) and uptake in allografts was significantly increased on post-transplant days 21 (5.2% vs. 0.9%; P=0.005) and 28 (4.8% vs. 0.9%; P=0.006) compared to isograft controls. Furthermore, [18F]FDG uptake correlated with an increase in rejection within allografts between days 14 and 28 post-transplant. Finally, the uptake of [13N]NH3 was significantly lower relative to the native heart in allografts with chronic vasculopathy compared to isograft controls on day 28 (P=0.01). Conclusions PET imaging with [18F]FDG can be used following transplantation to monitor the evolution of rejection. In addition, decreased uptake of [13N]NH3 in rejecting allografts may be reflective of decreased myocardial blood flow. These data suggest that combined [18F]FDG and [13N]NH3 PET imaging could be used as a non-invasive, quantitative technique for serial monitoring of allograft rejection and has potential application in human transplant recipients. PMID:25675207

Star-shaped poly(oligoethylene glycol) copolymer-based gels: Thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery.

PubMed

Soliman, Mahmoud E; Elmowafy, Enas; Casettari, Luca; Alexander, Cameron

2018-05-30

The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Association between Polymorphisms in MicroRNAs and Risk of Urological Cancer: A Meta-Analysis Based on 17,019 Subjects

PubMed Central

Wang, Yu-Hui; Hu, Han-Ning; Weng, Hong; Chen, Hao; Luo, Chang-Liang; Ji, Jia; Yin, Chang-Qing; Yuan, Chun-Hui; Wang, Fu-Bing

2017-01-01

Accumulating evidence has demonstrated that some single nucleotide polymorphisms (SNPs) existing in miRNAs correlate with the susceptibility to urological cancers. However, a clear consensus still not reached due to the limited statistical power in individual study. Thus, we concluded a meta-analysis to systematically evaluate the association between microRNA SNPs and urological cancer risk. Eligible studies were collected from PubMed, Embase, Web of Science, and CNKI databases. Pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to assess the strength of the relationships between three SNPs (miR-196a2, C>T rs11614913; miR-146a, G>C rs2910164; and miR-499, A>G rs3746444) and the risk of urological cancers. In addition, the stability of our analysis was evaluated by publication bias, sensitivity and heterogeneity analysis. Overall, a total of 17,019 subjects from 14 studies were included in this meta-analysis. We found that CT (miR-196a2, C>T rs11614913) was a risk factor for renal cell carcinoma (CT vs. CC: OR = 1.72, 95%CI = 1.05–2.80, P = 0.03, I2 = 66%), especially in Asian population (CT vs. CC: OR = 1.17, 95%CI = 1.04–1.32, P < 0.01, I2 = 0%). miR-146a G>C rs2910164 was a protective factor of urological cancers (C vs. G: OR = 0.87, 95%CI = 0.81–0.93, P < 0.01, I2 = 0%), especially for bladder cancer. miR-499 A>G rs3746444 was correlated with an increased risk of urological cancers, specifically in Asian population. In conclusion, our meta-analysis suggests that polymorphisms in microRNAs, miR-196a2, C>T rs11614913, miR-146a G>C rs2910164 and miR-499 A>G rs3746444, may be associated with the development of urological cancers and the risks mainly exist in Asian populations. PMID:28579964

Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance.

PubMed

Headen, Devon M; Woodward, Kyle B; Coronel, María M; Shrestha, Pradeep; Weaver, Jessica D; Zhao, Hong; Tan, Min; Hunckler, Michael D; Bowen, William S; Johnson, Christopher T; Shea, Lonnie; Yolcu, Esma S; García, Andrés J; Shirwan, Haval

2018-06-04

Islet transplantation is a promising therapy for type 1 diabetes. However, chronic immunosuppression to control rejection of allogeneic islets induces morbidities and impairs islet function. T effector cells are responsible for islet allograft rejection and express Fas death receptors following activation, becoming sensitive to Fas-mediated apoptosis. Here, we report that localized immunomodulation using microgels presenting an apoptotic form of the Fas ligand with streptavidin (SA-FasL) results in prolonged survival of allogeneic islet grafts in diabetic mice. A short course of rapamycin treatment boosted the immunomodulatory efficacy of SA-FasL microgels, resulting in acceptance and function of allografts over 200 days. Survivors generated normal systemic responses to donor antigens, implying immune privilege of the graft, and had increased CD4 + CD25 + FoxP3 + T regulatory cells in the graft and draining lymph nodes. Deletion of T regulatory cells resulted in acute rejection of established islet allografts. This localized immunomodulatory biomaterial-enabled approach may provide an alternative to chronic immunosuppression for clinical islet transplantation.

Rapid analysis of colipase gene variants by multicapillary electrophoresis.

PubMed

Jaczó, Zsuzsanna; Pál, Eszter; Dénes, Réka; Somogyi, Anikó; Sasvári-Székely, Mária; Guttman, András; Rónai, Zsolt

2015-06-01

Despite of the fact that the Human Genome Project was completed more than a decade ago, identification of the genetic background of polygenic diseases is still challenging. Several somewhat different approaches are available to investigate inheritable factors of complex phenotypes, all require, however efficient, high-throughput techniques for SNP genotyping. In this paper, we report a robust and reliable multiplex PCR-RFLP for genotype and haplotype analysis of six SNPs (rs41270082, rs3748051, rs142027015, rs3748048, rs73404011, and rs72925892) of the colipase (CLPS) gene. A multicapillary (12 capillaries) electrophoresis unit was used for high throughput and sensitive analysis of the digestion fragments. A Microsoft Excel-based spreadsheet was designed for the flexible visualization and evaluation of the electrophoretic separations, which is readily adaptable for any kind of electrophoresis application. Haplotype analysis of the two loci localized in close proximity of each other was carried out by molecular method, extended haplotypes including all five SNPs in the 5' upstream region were calculated. The techniques were applied in a case-control association study of type 2 diabetes mellitus. Although, single marker analysis did not reveal any significant association, it was observed that the rare GGCCG haplotype of the five 5' upstream region SNPs was about three times more frequent among patients compared to healthy control population. Our results demonstrated the applicability of multicapillary CGE in large-scale, high-throughput SNP analysis, and suggested that the CLPS gene polymorphisms might be considered as genetic risk factor for type 2 diabetes mellitus. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Can Glasgow-Blatchford Score and Pre-endoscopic Rockall Score Predict the Occurrence of Hypotension in Initially Normotensive Patients with Non-variceal Upper Gastrointestinal Bleeding?].

PubMed

Kim, June Sung; Ko, Byuk Sung; Son, Chang Hwan; Ahn, Shin; Seo, Dong Woo; Lee, Yoon Seon; Lee, Jae Ho; Oh, Bum Jin; Lim, Kyoung Soo; Kim, Won Young

2016-01-25

The aim of this study was to identify the ability of Glasgow-Blatchford score (GBS) and pre-endoscopic Rockall score (pre-E RS) to predict the occurrence of hypotension in patients with non-variceal upper gastrointestinal bleeding who are initially normotensive at emergency department. Retrospective observational study was conducted at Asan Medical Center emergency department (ED) in patients who presented with non-variceal upper gastrointestinal bleeding from January 1, 2011 to December 31, 2013. Study population was divided according to the development of hypotension, and demographics, comorbidities, and laboratory findings were compared. GBS and pre-E RS were estimated to predict the occurrence of hypotension. A total of 747 patients with non-variceal upper gastrointestinal bleeding were included during the study period, and 120 (16.1%) patients developed hypotension within 24 hours after ED admission. The median values GBS and pre-E RS were statistically different according to the occurrence of hypotension (8.0 vs. 10.0, 2.0 vs. 3.0, respectively; p<0.001). In the receiver operating characteristic curve analysis of hypotension development, the area under the curve of GBS and pre-E RS were 66% and 64%, respectively. The sensitivity and the specificity of GBS using optimal cut-off value were 81% and 46%, respectively, while those based on the pre-E RS were 74% and 46%, respectively. GBS and pre-E RS were both not sufficient for predicting the occurrence of hypotension in non-variceal upper gastrointestinal bleeding. Development of other scoring systems are needed.

SWIR dispersive Raman spectroscopy for discrimination of normal and malignant kidney tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Haifler, Miki; Pence, Isaac J.; Zisman, Amnon; Uzzo, Robert G.; Greenberg, Richard; Kutikov, Alexander; Smaldone, Marc; Chen, David; Viterbo, Rosalia; Ristau, Benjamin; Mahadevan-Jansen, Anita; Dumont, Alexander; Patil, Chetan A.

2017-02-01

Kidney cancer affects 65,000 new patients every. As computerized tomography became ubiquitous, the number of small, incidentally detected renal masses increased. About 6,000 benign cases are misclassified radiographically as malignant and removed surgically. Raman spectroscopy (RS) has been widely demonstrated for disease discrimination, however intense near-infrared auto-fluorescence of certain tissues (e.g kidney) can present serious challenges to bulk tissue diagnosis. A 1064nm excitation dispersive detection RS system demonstrated the ability to collect spectra with superior quality in tissues with strong auto-fluorescence. Our objective is to develop a 1064 nm dispersive detection RS system capable of differentiating normal and malignant renal tissue. We will report on the design and development of a clinical system for use in nephron sparing surgeries. We will present pilot data that has been collected from normal and malignant ex vivo kidney specimens using a benchtop RS system. A total of 93 measurements were collected from 12 specimens (6 Renal Cell Carcinoma, 6 Normal ). Spectral classification was performed using sparse multinomial logistic regression (SMLR). Correct classification by SMLR was obtained in 78% of the trials with sensitivity and specificity of 82% and 75% respectively. We will present the association of spectral features with biological indicators of healthy and diseased kidney tissue. Our findings indicate that 1064nm RS is a promising technique for differentiation of normal and malignant renal tissue. This indicates the potential for accurately separating healthy and cancerous tissues and suggests implications for utilizing RS for optical biopsy and surgical guidance in nephron sparing surgery.

The RTEL1 rs6010620 polymorphism and glioma risk: a meta-analysis based on 12 case-control studies.

PubMed

Du, Shu-Li; Geng, Ting-Ting; Feng, Tian; Chen, Cui-Ping; Jin, Tian-Bo; Chen, Chao

2014-01-01

The association between the RTEL1 rs6010620 single nucleotide polymorphism (SNP) and glioma risk has been extensively studied. However, the results remain inconclusive. To further examine this association, we performed a meta-analysis. A computerized search of the PubMed and Embase databases for publications regarding the RTEL1 rs6010620 polymorphism and glioma cancer risk was performed. Genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analyses, tests of heterogeneity, cumulative meta-analyses, and assessments of bias were performed in our meta-analysis. Our meta-analysis confirmed that risk with allele A is lower than with allele G for glioma. The A allele of rs6010620 in RTEL1 decreased the risk of developing glioma in the 12 case-control studies for all genetic models: the allele model (OR=0.752, 95%CI: 0.715-0.792), the dominant model (OR=0.729, 95%CI: 0.685-0.776), the recessive model (OR=0.647, 95%CI: 0.569-0.734), the homozygote comparison (OR=0.528, 95%CI: 0.456-0.612), and the heterozygote comparison (OR=0.761, 95%CI: 0.713-0.812). In all genetic models, the association between the RTEL1 rs6010620 polymorphism and glioma risk was significant. This meta-analysis suggests that the RTEL1 rs6010620 polymorphism may be a risk factor for glioma. Further functional studies evaluating this polymorphism and glioma risk are warranted.

Ligand-Mediated Activation of an Engineered Gs G Protein-Coupled Receptor in Osteoblasts Increases Trabecular Bone Formation

PubMed Central

Hsiao, Edward C.; Millard, Susan M.; Louie, Alyssa; Huang, Yong; Conklin, Bruce R.; Nissenson, Robert A.

2010-01-01

Age-dependent changes in skeletal growth play important roles in regulating skeletal expansion and in the course of many diseases affecting bone. How G protein-coupled receptor (GPCR) signaling affects these changes is poorly understood. Previously, we described a mouse model expressing Rs1, an engineered receptor with constitutive Gs activity. Rs1 expression in osteoblasts from gestation induced a dramatic age-dependent increase in trabecular bone with features resembling fibrous dysplasia; however, these changes were greatly minimized if Rs1 expression was delayed until after puberty. To further investigate whether ligand-induced activation of the Gs-GPCR pathway affects bone formation in adult mice, we activated Rs1 in adult mice with the synthetic ligand RS67333 delivered continuously via an osmotic pump or intermittently by daily injections. We found that osteoblasts from adult animals can be stimulated to form large amounts of bone, indicating that adult mice are sensitive to the dramatic bone- forming actions of Gs signaling in osteoblasts. In addition, our results show that intermittent and continuous activation of Rs1 led to structurally similar but quantitatively different degrees of trabecular bone formation. These results indicate that activation of a Gs-coupled receptor in osteoblasts of adult animals by either intermittent or continuous ligand administration can increase trabecular bone formation. In addition, osteoblasts located at the bone epiphyses may be more responsive to Gs signaling than osteoblasts at the bone diaphysis. This model provides a powerful tool for investigating the effects of ligand-activated Gs-GPCR signaling on dynamic bone growth and remodeling. PMID:20150184

Association between the BRCA2 rs144848 polymorphism and cancer susceptibility: a meta-analysis.

PubMed

Li, Qiuyan; Guan, Rongwei; Qiao, Yuandong; Liu, Chang; He, Ning; Zhang, Xuelong; Jia, Xueyuan; Sun, Haiming; Yu, Jingcui; Xu, Lidan

2017-06-13

The BRCA2 gene plays an important role in cancer carcinogenesis, and polymorphisms in this gene have been associated with cancer risk. The BRCA2 rs144848 polymorphism has been associated with several cancers, but results have been inconsistent. In the present study, a meta-analysis was performed to assess the association between the rs144848 polymorphism and cancer risk. Literature was searched from the databases of PubMed, Embase and Google Scholar before April 2016. The fixed or random effects model was used to calculate pooled odd ratios on the basis of heterogeneity. Meta-regression, sensitivity analysis, subgroup analysis and publication bias assessment were also performed using STATA 11.0 software according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009. A total of 40 relevant studies from 30 publications including 34,911 cases and 48,329 controls were included in the final meta-analysis. Among them, 22 studies focused on breast cancer, seven on ovarian cancer, five on non-Hodgkin lymphoma, and the remaining six studies examined various other cancers. The meta-analysis results showed that there were significant associations between the rs144848 polymorphism and cancer risk in all genetic models. Stratified by cancer type, the rs144848 polymorphism was associated with non-Hodgkin lymphoma. Stratified by study design, the allele model was associated with breast cancer risk in population-based studies. The meta-analysis suggests that the BRCA2 rs144848 polymorphism may play a role in cancer risk. Further well-designed studies are warranted to confirm these results.

Nest sanitation elicits egg discrimination in cuckoo hosts.

PubMed

Yang, Canchao; Chen, Min; Wang, Longwu; Liang, Wei; Møller, Anders Pape

2015-11-01

Nest sanitation is a nearly universal behavior in birds, while egg discrimination is a more specific adaptation that has evolved to counter brood parasitism. These two behaviors are closely related with nest sanitation being the ancestral behavior, and it has been hypothesized to constitute a preadaptation for egg discrimination. However, previous studies found little evidence to support this hypothesis. Here, we conducted an empirical test of the association between nest sanitation and egg discrimination in the barn swallow (Hirundo rustica) by inserting a single non-mimetic model egg or a non-mimetic model egg plus half a peanut shell into host nests. Compared to the rejection rate of single model eggs, barn swallows significantly increased egg rejection frequency if a half peanut shell was simultaneously introduced. Our result for the first time shows the impact of nest sanitation on egg discrimination and demonstrates that nest sanitation can elicit egg discrimination in hosts of brood parasites. This study provided evidence for nest sanitation being a preadaptation to egg discrimination by facilitating egg rejection, thereby significantly advancing our understanding of avian cognition of foreign objects. Furthermore, we suggest that egg discrimination behavior in many accepters and intermediate rejecters may be lost or diluted. Such egg discrimination can be elicited and restored after nest sanitation, implying a sensitive and rapid phenotypic response to increased risk of parasitism. Our study offers a novel perspective for investigating the role of so-called intermediate rejecter individuals or species in the long-term coevolutionary cycle between brood parasites and their hosts.

Characterisation of 2,4-Dinitroanisole: An Ingredient for Use in Low Sensitivity Melt Cast Formulations

DTIC Science & Technology

2006-08-01

PETN/TNT 50/50 PMMA Polymethyl methacrylate RDX Cyclotrimethylenetrinitramine RS-RDX Reduced Sensitivity RDX SEM Scanning electron... toxicological data was available on DNAN. It had been proposed that due to the increased solubility of DNAN over TNT in aqueous solution at biologically...While the toxicological study [18], concluded that the vapour pressure of DNAN was not sufficient to cause concerns over inhalation of DNAN during

Revisiting Short-Wave-Infrared (SWIR) Bands for Atmospheric Correction in Coastal Waters

NASA Technical Reports Server (NTRS)

Pahlevan, Nima; Roger, Jean-Claude; Ahmad, Ziauddin

2017-01-01

The shortwave infrared (SWIR) bands on the existing Earth Observing missions like MODIS have been designed to meet land and atmospheric science requirements. The future geostationary and polar-orbiting ocean color missions, however, require highly sensitive SWIR bands (greater than 1550nm) to allow for a precise removal of aerosol contributions. This will allow for reasonable retrievals of the remote sensing reflectance (R(sub rs)) using standard NASA atmospheric corrections over turbid coastal waters. Design, fabrication, and maintaining high-performance SWIR bands at very low signal levels bear significant costs on dedicated ocean color missions. This study aims at providing a full analysis of the utility of alternative SWIR bands within the 1600nm atmospheric window if the bands within the 2200nm window were to be excluded due to engineering/cost constraints. Following a series of sensitivity analyses for various spectral band configurations as a function of water vapor amount, we chose spectral bands centered at 1565 and 1675nm as suitable alternative bands within the 1600nm window for a future geostationary imager. The sensitivity of this band combination to different aerosol conditions, calibration uncertainties, and extreme water turbidity were studied and compared with that of all band combinations available on existing polar-orbiting missions. The combination of the alternative channels was shown to be as sensitive to test aerosol models as existing near-infrared (NIR) band combinations (e.g., 748 and 869nm) over clear open ocean waters. It was further demonstrated that while in extremely turbid waters the 1565/1675 band pair yields R(sub rs) retrievals as good as those derived from all other existing SWIR band pairs (greater than 1550nm), their total calibration uncertainties must be less than 1% to meet current science requirements for ocean color retrievals (i.e., delta R(sub rs) (443) less than 5%). We further show that the aerosol removal using the NIR and SWIR bands (available on the existing polar-orbiting missions) can be very sensitive to calibration uncertainties. This requires the need for monitoring the calibration of these bands to ensure consistent multi-mission ocean color products in coastal/inland waters.

Revisiting short-wave-infrared (SWIR) bands for atmospheric correction in coastal waters.

PubMed

Pahlevan, Nima; Roger, Jean-Claude; Ahmad, Ziauddin

2017-03-20

The shortwave infrared (SWIR) bands on the existing Earth Observing missions like MODIS have been designed to meet land and atmospheric science requirements. The future geostationary and polar-orbiting ocean color missions, however, require highly sensitive SWIR bands (> 1550nm) to allow for a precise removal of aerosol contributions. This will allow for reasonable retrievals of the remote sensing reflectance (R_rs) using standard NASA atmospheric corrections over turbid coastal waters. Design, fabrication, and maintaining high-performance SWIR bands at very low signal levels bear significant costs on dedicated ocean color missions. This study aims at providing a full analysis of the utility of alternative SWIR bands within the 1600nm atmospheric window if the bands within the 2200nm window were to be excluded due to engineering/cost constraints. Following a series of sensitivity analyses for various spectral band configurations as a function of water vapor amount, we chose spectral bands centered at 1565 and 1675nm as suitable alternative bands within the 1600nm window for a future geostationary imager. The sensitivity of this band combination to different aerosol conditions, calibration uncertainties, and extreme water turbidity were studied and compared with that of all band combinations available on existing polar-orbiting missions. The combination of the alternative channels was shown to be as sensitive to test aerosol models as existing near-infrared (NIR) band combinations (e.g., 748 and 869nm) over clear open ocean waters. It was further demonstrated that while in extremely turbid waters the 1565/1675 band pair yields R_rs retrievals as good as those derived from all other existing SWIR band pairs (> 1550nm), their total calibration uncertainties must be < 1% to meet current science requirements for ocean color retrievals (i.e., Δ R_rs (443) < 5%). We further show that the aerosol removal using the NIR and SWIR bands (available on the existing polar-orbiting missions) can be very sensitive to calibration uncertainties. This requires the need for monitoring the calibration of these bands to ensure consistent multi-mission ocean color products in coastal/inland waters.

Combined Raman spectroscopy and autofluoresence imaging method for in vivo skin tumor diagnosis

NASA Astrophysics Data System (ADS)

Zakharov, V. P.; Bratchenko, I. A.; Myakinin, O. O.; Artemyev, D. N.; Khristoforova, Y. A.; Kozlov, S. V.; Moryatov, A. A.

2014-09-01

The fluorescence and Raman spectroscopy (RS) combined method of in vivo detection of malignant human skin cancer was demonstrated. The fluorescence analysis was used for detection of abnormalities during fast scanning of large tissue areas. In suspected cases of malignancy the Raman spectrum analysis of biological tissue was performed to determine the type of neoplasm. A special RS phase method was proposed for in vivo identification of skin tumor. Quadratic Discriminant Analysis was used for tumor type classification on phase planes. It was shown that the application of phase method provides a diagnosis of malignant melanoma with a sensitivity of 89% and a specificity of 87%.

Detection of questionable occlusal carious lesions using an electrical bioimpedance method with fractional electrical model

NASA Astrophysics Data System (ADS)

Morais, A. P.; Pino, A. V.; Souza, M. N.

2016-08-01

This in vitro study evaluated the diagnostic performance of an alternative electric bioimpedance spectroscopy technique (BIS-STEP) detect questionable occlusal carious lesions. Six specialists carried out the visual (V), radiography (R), and combined (VR) exams of 57 sound or non-cavitated occlusal carious lesion teeth classifying the occlusal surfaces in sound surface (H), enamel caries (EC), and dentinal caries (DC). Measurements were based on the current response to a step voltage excitation (BIS-STEP). A fractional electrical model was used to predict the current response in the time domain and to estimate the model parameters: Rs and Rp (resistive parameters), and C and α (fractional parameters). Histological analysis showed caries prevalence of 33.3% being 15.8% hidden caries. Combined examination obtained the best traditional diagnostic results with specificity = 59.0%, sensitivity = 70.9%, and accuracy = 60.8%. There were statistically significant differences in bioimpedance parameters between the H and EC groups (p = 0.016) and between the H and DC groups (Rs, p = 0.006; Rp, p = 0.022, and α, p = 0.041). Using a suitable threshold for the Rs, we obtained specificity = 60.7%, sensitivity = 77.9%, accuracy = 73.2%, and 100% of detection for deep lesions. It can be concluded that BIS-STEP method could be an important tool to improve the detection and management of occlusal non-cavitated primary caries and pigmented sites.

Functional connectivity density mapping: comparing multiband and conventional EPI protocols.

PubMed

Cohen, Alexander D; Tomasi, Dardo; Shokri-Kojori, Ehsan; Nencka, Andrew S; Wang, Yang

2018-06-01

Functional connectivity density mapping (FCDM) is a newly developed data-driven technique that quantifies the number of local and global functional connections for each voxel in the brain. In this study, we evaluated reproducibility, sensitivity, and specificity of both local functional connectivity density (lFCD) and global functional connectivity density (gFCD). We compared these metrics using the human connectome project (HCP) compatible high-resolution (2 mm isotropic, TR = 0.8 s) multiband (MB), and more typical, lower resolution (3.5 mm isotropic, TR = 2.0 s) single-band (SB) resting state functional MRI (rs-fMRI) acquisitions. Furthermore, in order to be more clinically feasible, only rs-fMRI scans that lasted seven minutes were tested. Subjects were scanned twice within a two-week span. We found sensitivity and specificity increased and reproducibility either increased or did not change for the MB compared to the SB acquisitions. The MB scans also showed improved gray matter/white matter contrast compared to the SB scans. The lFCD and gFCD patterns were similar across MB and SB scans and confined predominantly to gray matter. We also observed a strong spatial correlation of FCD between MB and SB scans indicating the two acquisitions provide similar information. These findings indicate high-resolution MB acquisitions improve the quality of FCD data, and seven minute rs-fMRI scan can provide robust FCD measurements.

Transcutaneous in vivo Raman spectroscopic studies in a mouse model: evaluation of changes in the breast associated with pregnancy and lactation

NASA Astrophysics Data System (ADS)

Bhattacharjee, Tanmoy; Maru, Girish; Ingle, Arvind; Krishna, C. Murali

2013-04-01

Raman spectroscopy (RS) has been extensively explored as an alternative diagnostic tool for breast cancer. This can be attributed to its sensitivity to malignancy-associated biochemical changes. However, biochemical changes due to nonmalignant conditions like benign lesions, inflammatory diseases, aging, menstrual cycle, pregnancy, and lactation may act as confounding factors in diagnosis of breast cancer. Therefore, in this study, the efficacy of RS to classify pregnancy and lactation-associated changes as well as its effect on breast tumor diagnosis was evaluated. Since such studies are difficult in human subjects, a mouse model was used. Spectra were recorded transcutaneously from the breast region of six Swiss bare mice postmating, during pregnancy, and during lactation. Data were analyzed using multivariate statistical tool Principal Component-Linear Discriminant Analysis. Results suggest that RS can differentiate breasts of pregnant/lactating mice from those of normal mice, the classification efficiencies being 100%, 60%, and 88% for normal, pregnant, and lactating mice, respectively. Frank breast tumors could be classified with 97.5% efficiency, suggesting that these physiological changes do not affect the ability of RS to detect breast tumors.

A simulation model for risk assessment of turbine wheels

NASA Technical Reports Server (NTRS)

Safie, Fayssal M.; Hage, Richard T.

1991-01-01

A simulation model has been successfully developed to evaluate the risk of the Space Shuttle auxiliary power unit (APU) turbine wheels for a specific inspection policy. Besides being an effective tool for risk/reliability evaluation, the simulation model also allows the analyst to study the trade-offs between wheel reliability, wheel life, inspection interval, and rejection crack size. For example, in the APU application, sensitivity analysis results showed that the wheel life limit has the least effect on wheel reliability when compared to the effect of the inspection interval and the rejection crack size. In summary, the simulation model developed represents a flexible tool to predict turbine wheel reliability and study the risk under different inspection policies.

A simulation model for risk assessment of turbine wheels

NASA Astrophysics Data System (ADS)

Safie, Fayssal M.; Hage, Richard T.

A simulation model has been successfully developed to evaluate the risk of the Space Shuttle auxiliary power unit (APU) turbine wheels for a specific inspection policy. Besides being an effective tool for risk/reliability evaluation, the simulation model also allows the analyst to study the trade-offs between wheel reliability, wheel life, inspection interval, and rejection crack size. For example, in the APU application, sensitivity analysis results showed that the wheel life limit has the least effect on wheel reliability when compared to the effect of the inspection interval and the rejection crack size. In summary, the simulation model developed represents a flexible tool to predict turbine wheel reliability and study the risk under different inspection policies.

Pulse shape discrimination for background rejection in germanium gamma-ray detectors

NASA Technical Reports Server (NTRS)

Feffer, P. T.; Smith, D. M.; Campbell, R. D.; Primbsch, J. H.; Lin, R. P.

1989-01-01

A pulse-shape discrimination (PSD) technique is developed to reject the beta-decay background resulting from activation of Ge gamma-ray detectors by cosmic-ray secondaries. These beta decays are a major source of background at 0.2-2 MeV energies in well shielded Ge detector systems. The technique exploits the difference between the detected current pulse shapes of single- and multiple-site energy depositions within the detector: beta decays are primarily single-site events, while photons at these energies typically Compton scatter before being photoelectrically absorbed to produce multiple-site events. Depending upon the amount of background due to sources other than beta decay, PSD can more than double the detector sensitivity.

[Diurnal and Seasonal Dynamic Variation of Soil Respiration and Its Influencing Factors of Different Fenced Enclosure Years in Desert Steppec].

PubMed

Cui, Hai; Zhang, Ya-hong

2016-04-15

The fenced measures could improve the ecological environment of degraded grassland, it's a main measure for restoration of degraded grassland vegetation in China. Soil respiration (Rs) is an important component of an ecosystem's carbon cycle and the main pathway for carbon moving from the ecosystem to the atmosphere. In order to explore soil respiration characteristics and influencing factors of the different fenced years in arid desert grassland, we continuously observed Rs rate and environmental factors in the growing season of fenced enclosure 11a, 7a and no fenced (CK) desert steppe in Ningxia. The results showed that: (1) Both the diurnal andseasonal variations of Rs rate showed a single asymmetric peak changing in fenced enclosure of 11 years, 7 years, CK desert steppe. On the daily scale, the maximum and minimum values of Rs rate were found in the periods of 12:00-16:00 and 00:00-06:00,respectively. On the seasonal variation scale, the maximum value of Rs rate occurred in August with suitable precipitation and temperature conditions. And the Rs rate of the growing season of different fenced enclosure years was in the order of 11a [0.143 g · (m² · h)⁻¹] > 7a [0.138 g · (m² · h)⁻¹] > CK [0.106 g · (m2 - h)⁻¹]. (2) According to statistical analysis, it indicated that R² rate had a significant exponential positive relationship with air and soil temperature in fenced enclosure of 11 years, 7 years, CK desert steppe (P < 0.01). The order of the correlation of Rs rate and temperature was shown as soil surface temperature (R²: 0.408-0.413) > air temperature (R2: 0.355-0.376) > 5-20 cm soil temperature (R2: 0.263-0.394). The temperature sensitivity coefficient Q, increased gradually with the soil depth, and Q1, of different fenced enclosure years was showed as 11 a (2.728) > 7a (2.436) > CK (2.086). (3) A significant quadratic function model (P < 0.05) was observed for the relationship between Rs rate and relative air humidity, soil moisture content of fenced enclosure 11a, 7a and CK desert steppe in the whole growing season. Rs rate had a significant linear negative correlation with air carbon dioxide concentration (P < 0.01), a linear positive correlation with the windspeed (P < 0.05), and a significant weak linear positive correlation with light intensity (P < 0.01). (4) It showed that Rs increasedwith increasing fenced closure years in arid desert steppe, and temperature sensitivity coefficient Q₁₀ also increased with increasing fenced enclosure years. To sum up, 0-20 cm soil temperature and moisture were the main influencing factors of soil respiration of desert steppe. This study has important implications to understand the role that different fenced enclosure years play in carbon emission. Such information will lay a foundation for assessing carbon source or carbon sequestration of different fenced enclosure years in desert steppe. Therefore, our research results have important function for better managing grassland in desert steppe in Ningxia and other arid and semiarid areas of North China.

Parental acceptance, postpartum depression, and maternal sensitivity: mediating and moderating processes.

PubMed

Crockenberg, Susan C; Leerkes, Esther M

2003-03-01

Mothers (n = 92), fathers (n = 84), and their infants (60% male) participated in a longitudinal study of postpartum depression and maternal sensitivity. Mothers completed questionnaire measures of remembered parental acceptance, depressive symptoms, and infant distress to novelty and limits. Mothers and partners reported on marital aggression and avoidance. Maternal sensitivity was observed in the laboratory at 6 months. Characteristics of mothers, partners, and infants combined to predict postpartum depression and maternal sensitivity. Remembered parental rejection predicted postpartum depressive symptoms with prenatal depression controlled; self-esteem mediated this effect. Paternal acceptance buffered against postpartum depression when infants were highly reactive and when partners were aggressive. Paternal acceptance reduced the impact of postpartum depression on maternal sensitivity; having an aggressive marital partner exacerbated the effect.

Image Corruption Detection in Diffusion Tensor Imaging for Post-Processing and Real-Time Monitoring

PubMed Central

Li, Yue; Shea, Steven M.; Lorenz, Christine H.; Jiang, Hangyi; Chou, Ming-Chung; Mori, Susumu

2013-01-01

Due to the high sensitivity of diffusion tensor imaging (DTI) to physiological motion, clinical DTI scans often suffer a significant amount of artifacts. Tensor-fitting-based, post-processing outlier rejection is often used to reduce the influence of motion artifacts. Although it is an effective approach, when there are multiple corrupted data, this method may no longer correctly identify and reject the corrupted data. In this paper, we introduce a new criterion called “corrected Inter-Slice Intensity Discontinuity” (cISID) to detect motion-induced artifacts. We compared the performance of algorithms using cISID and other existing methods with regard to artifact detection. The experimental results show that the integration of cISID into fitting-based methods significantly improves the retrospective detection performance at post-processing analysis. The performance of the cISID criterion, if used alone, was inferior to the fitting-based methods, but cISID could effectively identify severely corrupted images with a rapid calculation time. In the second part of this paper, an outlier rejection scheme was implemented on a scanner for real-time monitoring of image quality and reacquisition of the corrupted data. The real-time monitoring, based on cISID and followed by post-processing, fitting-based outlier rejection, could provide a robust environment for routine DTI studies. PMID:24204551

A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation

PubMed Central

Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A.; Gong, Yongquan; Fischbein, Michael P.; Robbins, Robert C.; Naesens, Maarten

2013-01-01

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design. PMID:24127489

A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

PubMed

Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

2013-10-21

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

The Role of the Posterior Temporal and Medial Prefrontal Cortices in Mediating Learning from Romantic Interest and Rejection

PubMed Central

Cooper, Jeffrey C.; Dunne, Simon; Furey, Teresa; O'Doherty, John P.

2014-01-01

Romantic interest or rejection can be powerful incentives not merely for their emotional impact, but for their potential to transform, in a single interaction, what we think we know about another person—or ourselves. Little is known, though, about how the brain computes expectations for, and learns from, real-world romantic signals. In a novel “speed-dating” paradigm, we had participants meet potential romantic partners in a series of 5-min “dates,” and decide whether they would be interested in seeing each partner again. Afterward, participants were scanned with functional magnetic resonance imaging while they were told, for the first time, whether that partner was interested in them or rejected them. Expressions of interest and rejection activated regions previously associated with “mentalizing,” including the posterior superior temporal sulcus (pSTS) and rostromedial prefrontal cortex (RMPFC); while pSTS responded to differences from the participant's own decision, RMPFC responded to prediction errors from a reinforcement-learning model of personal desirability. Responses in affective regions were also highly sensitive to participants' expectations. Far from being inscrutable, then, responses to romantic expressions seem to involve a quantitative learning process, rooted in distinct sources of expectations, and encoded in neural networks that process both affective value and social beliefs. PMID:23599165

Prediction of alcohol drinking in adolescents: Personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity.

PubMed

Heinrich, Angela; Müller, Kathrin U; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Papadopoulos, Dimitri; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Mann, Karl; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Smolka, Michael; Ströhle, Andreas; Rietschel, Marcella; Flor, Herta; Schumann, Gunter; Nees, Frauke

2016-07-01

Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age=14.37) and again later (mean age=16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced. Copyright © 2016 Elsevier B.V. All rights reserved.

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

PubMed

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). We confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD. These results give us supporting evidence that DNA methylation mediates genetic effects on disease susceptibility.

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease

PubMed Central

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Background Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. Methods CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score (ΔRAS¯) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing ΔRAS¯ >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. Results We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of ΔRAS¯ (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 (ΔRAS¯ = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). Conclusions We confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD. These results give us supporting evidence that DNA methylation mediates genetic effects on disease susceptibility. PMID:29547621

Kidney transplantation after desensitization in sensitized patients: a Korean National Audit.

PubMed

Huh, Kyu Ha; Kim, Beom Seok; Yang, Jaeseok; Ahn, Jeongmyung; Kim, Myung-Gyu; Park, Jae Berm; Kim, Jong Man; Chung, Byung-Ha; Kim, Joong Kyung; Kong, Jin Min

2012-10-01

The number of end-stage renal disease (ESRD) patients with preformed antibodies waiting for a kidney transplant has been increasing lately. We conducted a nationwide study on the outcomes of kidney transplantation after desensitization in Korea. Six transplant centers have run desensitization programs. The patients who underwent living donor kidney transplantation after desensitization from 2002 to 2010 were retrospectively analyzed. A total of 86 cases were enrolled. Thirty-five of these were cases of re-transplantation (40.7 %). Indications of desensitization were positive complement-dependent cytotoxicity (CDC) cross-match responses (CDC(+), 36.0 %), positive flow-cytometric cross-match responses (FCX(+), 54.7 %), and positive donor-specific antibodies (DSA(+), 8.1 %). The desensitization protocols used pre-transplant plasmapheresis (95.3 %), intravenous immunoglobulin (62.8 %), and rituximab (67.4 %). Acute rejection occurred in 18 patients (20.9 %), graft failure occurred in 4 patients, and the 3-year graft survival rate was 93.8 %. The presence of DSA increased the acute rejection rate (P = 0.015) and decreased the 1-year post-transplant estimated glomerular filtration rate (P = 0.006). Although rejection-free survival rates did not differ significantly between the CDC(+) and FCX(+) groups, the 1-year estimated glomerular filtration rate was lower in the CDC(+) group (P = 0.010). Infectious and significant bleeding complications occurred in 15.5 % and 4.7 % of cases, respectively. Kidney transplantation after desensitization had good graft outcomes and tolerable complications in Korea, and therefore, this therapy can be recommended for sensitized ESRD patients.

A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order.

PubMed

Ramasamy, Adaikalavan; Curjuric, Ivan; Coin, Lachlan J; Kumar, Ashish; McArdle, Wendy L; Imboden, Medea; Leynaert, Benedicte; Kogevinas, Manolis; Schmid-Grendelmeier, Peter; Pekkanen, Juha; Wjst, Matthias; Bircher, Andreas J; Sovio, Ulla; Rochat, Thierry; Hartikainen, Anna-Liisa; Balding, David J; Jarvelin, Marjo-Riitta; Probst-Hensch, Nicole; Strachan, David P; Jarvis, Deborah L

2011-11-01

Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P(grass) = 1.6 × 10(-9); P(AR) = 8.0 × 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P(grass) = 9.4 × 10(-9); P(AR) = 3.8 × 10(-8)). The third genome-wide significant variant was rs17513503 (P(grass) = 1.2 × 10(-8); PAR = 7.4 × 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.