Ethnic differences in Glycaemic control in people with type 2 diabetes mellitus living in Scotland

Background and Aims: Previous studies have investigated the association between ethnicity and processes of care and intermediate outcomes of diabetes, but there are limited population-based studies available. The aim of this study was to use population-based data to investigate the relationships between ethnicity and glycaemic control in men and women with diabetes mellitus living in Scotland.<p></p> Methods: We used a 2008 extract from the population-based national electronic diabetes database of Scotland. The association between ethnicity with mean glycaemic control in type 2 diabetes mellitus was examined in a retrospective cohort study, including adjustment for a number of variables including age, sex, socioeconomic status, body mass index (BMI), prescribed treatment and duration of diabetes.<p></p> Results: Complete data for analyses were available for 56,333 White Scottish adults, 2,535 Pakistanis, 857 Indians, 427 Chinese and 223 African-Caribbeans. All other ethnic groups had significantly (p<0.05) greater proportions of people with suboptimal glycaemic control (HbA1c >58 mmol/mol, 7.5%) compared to the White Scottish group, despite generally younger mean age and lower BMI. Fully adjusted odds ratios for suboptimal glycaemic control were significantly higher among Pakistanis and Indians (1.85, 95% CI: 1.68–2.04, and 1.62,95% CI: 1.38–1.89) respectively.<p></p> Conclusions: Pakistanis and Indians with type 2 diabetes mellitus were more likely to have suboptimal glycaemic control than the white Scottish population. Further research on health services and self-management are needed to understand the association between ethnicity and glycaemic control to address ethnic disparities in glycaemic control.<p></p&gt

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Small RNA analysis in Sindbis virus infected human HEK293 cells

In contrast to the defence mechanism of RNA interference (RNAi) in plants and invertebrates, its role in the innate response to virus infection of mammals is a matter of debate. Since RNAi has a well-established role in controlling infection of the alphavirus Sindbis virus (SINV) in insects, we have used this virus to investigate the role of RNAi in SINV infection of human cells

The Effects of Hydration on Growth of the House Cricket, Acheta domesticus

Maintenance of biochemical gradients, membrane fluidity, and sustained periods of activity are key physiological and behavioral functions of water for animals living in desiccating environments. Water stress may reduce the organism's ability to maintain these functions and as such, may reduce an organism's growth. However, few studies have examined this potential effect. The effects of altered hydration state of the house cricket, Acheta domesticus L. (Orthoptera: Gryllidae) on individual growth were studied under laboratory conditions. Crickets were permitted access to water for three different durations each day, resulting in significant differences in hydration state (32% greater hydration for maximum than minimum duration of water availability). Growth was 59% and 72% greater in dry mass and length, respectively, between the lowest and highest hydration state treatments. These findings may be representative for a variety of animal species and environments and could have important ecological implications

Testing the role of predicted gene knockouts in human anthropometric trait variation

National Heart, Lung, and Blood Institute (NHLBI) S.L. is funded by a Canadian Institutes of Health Research Banting doctoral scholarship. G.L. is funded by Genome Canada and Génome Québec; the Canada Research Chairs program; and the Montreal Heart Institute Foundation. C.M.L. is supported by Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A); and the Li Ka Shing Foundation. N.S. is funded by National Institutes of Health (grant numbers HL088456, HL111089, HL116747). The Mount Sinai BioMe Biobank Program is supported by the Andrea and Charles Bronfman Philanthropies. GO ESP is supported by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO, RC2 HL-102924 to WHISP). The ESP exome sequencing was performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL- 102926 to SeattleGO). EGCUT work was supported through the Estonian Genome Center of University of Tartu by the Targeted Financing from the Estonian Ministry of Science and Education (grant number SF0180142s08); the Development Fund of the University of Tartu (grant number SP1GVARENG); the European Regional Development Fund to the Centre of Excellence in Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and through FP7 (grant number 313010). EGCUT were further supported by the US National Institute of Health (grant number R01DK075787). A.K.M. was supported by an American Diabetes Association Mentor-Based Postdoctoral Fellowship (#7-12-MN- 02). The BioVU dataset used in the analyses described were obtained from Vanderbilt University Medical Centers BioVU which is supported by institutional funding and by the Vanderbilt CTSA grant ULTR000445 from NCATS/NIH. Genome-wide genotyping was funded by NIH grants RC2GM092618 from NIGMS/OD and U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access publication charges for this article was provided by a block grant from Research Councils UK to the University of Cambridge

Testing the role of predicted gene knockouts in human anthropometric trait variation

National Heart, Lung, and Blood Institute (NHLBI) S.L. is funded by a Canadian Institutes of Health Research Banting doctoral scholarship. G.L. is funded by Genome Canada and Génome Québec; the Canada Research Chairs program; and the Montreal Heart Institute Foundation. C.M.L. is supported by Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A); and the Li Ka Shing Foundation. N.S. is funded by National Institutes of Health (grant numbers HL088456, HL111089, HL116747). The Mount Sinai BioMe Biobank Program is supported by the Andrea and Charles Bronfman Philanthropies. GO ESP is supported by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO, RC2 HL-102924 to WHISP). The ESP exome sequencing was performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL- 102926 to SeattleGO). EGCUT work was supported through the Estonian Genome Center of University of Tartu by the Targeted Financing from the Estonian Ministry of Science and Education (grant number SF0180142s08); the Development Fund of the University of Tartu (grant number SP1GVARENG); the European Regional Development Fund to the Centre of Excellence in Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and through FP7 (grant number 313010). EGCUT were further supported by the US National Institute of Health (grant number R01DK075787). A.K.M. was supported by an American Diabetes Association Mentor-Based Postdoctoral Fellowship (#7-12-MN- 02). The BioVU dataset used in the analyses described were obtained from Vanderbilt University Medical Centers BioVU which is supported by institutional funding and by the Vanderbilt CTSA grant ULTR000445 from NCATS/NIH. Genome-wide genotyping was funded by NIH grants RC2GM092618 from NIGMS/OD and U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access publication charges for this article was provided by a block grant from Research Councils UK to the University of Cambridge

Cell-Type Specific Expression of a Dominant Negative PKA Mutation in Mice

We employed the Cre recombinase/loxP system to create a mouse line in which PKA activity can be inhibited in any cell-type that expresses Cre recombinase. The mouse line carries a mutant Prkar1a allele encoding a glycine to aspartate substitution at position 324 in the carboxy-terminal cAMP-binding domain (site B). This mutation produces a dominant negative RIα regulatory subunit (RIαB) and leads to inhibition of PKA activity. Insertion of a loxP-flanked neomycin cassette in the intron preceding the site B mutation prevents expression of the mutant RIαB allele until Cre-mediated excision of the cassette occurs. Embryonic stem cells expressing RIαB demonstrated a reduction in PKA activity and inhibition of cAMP-responsive gene expression. Mice expressing RIαB in hepatocytes exhibited reduced PKA activity, normal fasting induced gene expression, and enhanced glucose disposal. Activation of the RIαB allele in vivo provides a novel system for the analysis of PKA function in physiology

Testing the role of predicted gene knockouts in human anthropometric trait variation

National Heart, Lung, and Blood Institute (NHLBI) S.L. is funded by a Canadian Institutes of Health Research Banting doctoral scholarship. G.L. is funded by Genome Canada and Génome Québec; the Canada Research Chairs program; and the Montreal Heart Institute Foundation. C.M.L. is supported by Wellcome Trust (grant numbers 086596/Z/08/Z, 086596/Z/08/A); and the Li Ka Shing Foundation. N.S. is funded by National Institutes of Health (grant numbers HL088456, HL111089, HL116747). The Mount Sinai BioMe Biobank Program is supported by the Andrea and Charles Bronfman Philanthropies. GO ESP is supported by NHLBI (RC2 HL-103010 to HeartGO, RC2 HL-102923 to LungGO, RC2 HL-102924 to WHISP). The ESP exome sequencing was performed through NHLBI (RC2 HL-102925 to BroadGO, RC2 HL- 102926 to SeattleGO). EGCUT work was supported through the Estonian Genome Center of University of Tartu by the Targeted Financing from the Estonian Ministry of Science and Education (grant number SF0180142s08); the Development Fund of the University of Tartu (grant number SP1GVARENG); the European Regional Development Fund to the Centre of Excellence in Genomics (EXCEGEN) [grant number 3.2.0304.11-0312]; and through FP7 (grant number 313010). EGCUT were further supported by the US National Institute of Health (grant number R01DK075787). A.K.M. was supported by an American Diabetes Association Mentor-Based Postdoctoral Fellowship (#7-12-MN- 02). The BioVU dataset used in the analyses described were obtained from Vanderbilt University Medical Centers BioVU which is supported by institutional funding and by the Vanderbilt CTSA grant ULTR000445 from NCATS/NIH. Genome-wide genotyping was funded by NIH grants RC2GM092618 from NIGMS/OD and U01HG004603 from NHGRI/NIGMS. Funding to pay the Open Access publication charges for this article was provided by a block grant from Research Councils UK to the University of Cambridge

The Raine study had no evidence of significant perinatal selection bias after two decades of follow up: A longitudinal pregnancy cohort study

Background: Cohort studies may increase or decrease their selection bias as they progress through time. The Western Australian Pregnancy Cohort (Raine) Study has followed 2868 children for over two decades; from fetal into adult life. This paper analyses the cohort over time, assessing potential bias that may come and go with recruitment, retention and loss of participants. Methods: Linked data from all births in Western Australian over the 3 years the Raine Cohort was recruited were obtained to compare perinatal characteristics and subsequent health outcomes between the Western Australian (WA) contemporaneous birth population and the Raine Cohort at five time points. Perinatal exposure-outcome comparisons were employed to assess bias due to non-participation in Raine Study subsets. Results: There were demographic differences between the Raine Study cohort and its source population at recruitment with further changes across the period of follow up. Despite these differences, the pregnancy and infant data of those with continuing participation were not significantly different to the WA contemporaneous birth population. None of the exposure-outcome associations were significantly different to those in the WA general population at recruitment or at any cohort reviews suggesting no substantial recruitment or attrition bias. Conclusions: The Raine Study is valuable for association studies, even after 20 years of cohort reviews with increasing non-participation of cohort members. Non-participation has resulted in greater attrition of socially disadvantaged participants, however, exposure-outcome association analyses suggest that there is no apparent resulting selection bias

Similarities and Differences in Chinese and Caucasian Adults' Use of Facial Cues for Trustworthiness Judgments

All cultural groups in the world place paramount value on interpersonal trust. Existing research suggests that although accurate judgments of another's trustworthiness require extensive interactions with the person, we often make trustworthiness judgments based on facial cues on the first encounter. However, little is known about what facial cues are used for such judgments and what the bases are on which individuals make their trustworthiness judgments.In the present study, we tested the hypothesis that individuals may use facial attractiveness cues as a “shortcut” for judging another's trustworthiness due to the lack of other more informative and in-depth information about trustworthiness. Using data-driven statistical models of 3D Caucasian faces, we compared facial cues used for judging the trustworthiness of Caucasian faces by Caucasian participants who were highly experienced with Caucasian faces, and the facial cues used by Chinese participants who were unfamiliar with Caucasian faces. We found that Chinese and Caucasian participants used similar facial cues to judge trustworthiness. Also, both Chinese and Caucasian participants used almost identical facial cues for judging trustworthiness and attractiveness.The results suggest that without opportunities to interact with another person extensively, we use the less racially specific and more universal attractiveness cues as a “shortcut” for trustworthiness judgments