Evaluating the association of common APOA2 variants with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p><it>APOA2 </it>is a positional and biological candidate gene for type 2 diabetes at the chromosome 1q21-q24 susceptibility locus. The aim of this study was to examine if HapMap phase II tag SNPs in <it>APOA2 </it>are associated with type 2 diabetes and quantitative traits in French Caucasian subjects.</p> <p>Methods</p> <p>We genotyped the three HapMap phase II tagging SNPs (rs6413453, rs5085 and rs5082) required to capture the common variation spanning the <it>APOA2 </it>locus in our type 2 diabetes case-control cohort comprising 3,093 French Caucasian subjects. The association between these variants and quantitative traits was also examined in the normoglycaemic adults of the control cohort. In addition, meta-analysis of publicly available whole genome association data was performed.</p> <p>Results</p> <p>None of the <it>APOA2 </it>tag SNPs were associated with type 2 diabetes in the French Caucasian case-control cohort (rs6413453, <it>P </it>= 0.619; rs5085, <it>P </it>= 0.245; rs5082, <it>P </it>= 0.591). However, rs5082 was marginally associated with total cholesterol levels (<it>P </it>= 0.026) and waist-to-hip ratio (<it>P </it>= 0.029). The meta-analysis of data from 12,387 subjects confirmed our finding that common variation at the <it>APOA2 </it>locus is not associated with type 2 diabetes.</p> <p>Conclusion</p> <p>The available data does not support a role for common variants in <it>APOA2 </it>on type 2 diabetes susceptibility or related quantitative traits in Northern Europeans.</p

Patterns of genetic diversity and differentiation in the tsetse fly Glossina morsitans morsitans Westwood populations in East and southern Africa

Genetic diversity and differentiation within and among nine G. morsitans morsitanspopulations from East and southern Africa was assessed by examining variation at seven microsatellite loci and a mitochondrial locus, cytochrome oxidase (COI). Mean COI diversity within populations was 0.63 ± 0.33 and 0.81 taken over all populations. Diversities averaged over microsatellite loci were high (mean number of alleles/locus ≥7.4; mean H E ≥ 65%) in all populations. Diversities averaged across populations were greater in East Africa (mean number of alleles = 22 ± 2.6; mean h e = 0.773 ± 0.033) than in southern Africa (mean number of alleles = 18.7 ± 4.0; mean h e = 0.713 ± 0.072). Differentiation among all populations was highly significant (R ST = 0.25, F ST = 0.132). Nei’s G ij statistics were 0.09 and 0.19 within regions for microsatellites and mitochondria, respectively; between regions, G ij was 0.14 for microsatellites and 0.23 for mitochondria. G ST among populations was 0.23 for microsatellite loci and 0.40 for mitochondria. The F, G and R statistics indicate highly restricted gene flow among G. m. morsitans populations separated over geographic scales of 12–917 km

A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling

Nanoparticles are now emerging as a novel class of autophagy activators. Functionalized single-walled carbon nanotubes (f-SWCNTs) are valuable nanomaterials in many industries. This article is designed to assess the autophagic response for f-SWCNTs exposure in vitro and in vivo. A few types of f-SWCNTs were screened in human lung adenocarcinoma A549 cells for the autophagic response and related pathways in vitro. Formation of autophagosomes and LC3-II upregulation were confirmed on the basis of electron microscopy and LC3 western blotting for COOH-CNT, but not for PABS-CNT and PEG-CNT. MTT assay showed marked increase in cell viability, when COOH-CNT was added to cells in the presence of autophagy inhibitor 3MA, ATG6 or TSC2 siRNA. Consistent with the involvement of the Akt–TSC1/2–mTOR pathway, the phosphorylation levels of mTOR, mTOR's substrate S6 and Akt were shown significantly decreased in A549 cells on treatment with COOH-CNT using western blotting. What's more, autophagy inhibitor 3MA significantly reduced the lung edema in vivo. In a word, COOH-CNT induced autophagic cell death in A549 cells through the AKT–TSC2–mTOR pathway and caused acute lung injury in vivo. Inhibition of autophagy significantly reduced COOH-CNT-induced autophagic cell death and ameliorated acute lung injury in mice, suggesting a potential remedy to address the growing concerns on the safety of nanomaterials

Gene Flow and Genetic Diversity of a Broadcast-Spawning Coral in Northern Peripheral Populations

Recently, reef-building coral populations have been decreasing worldwide due to various disturbances. Population genetic studies are helpful for estimating the genetic connectivity among populations of marine sessile organisms with metapopulation structures such as corals. Moreover, the relationship between latitude and genetic diversity is informative when evaluating the fragility of populations. In this study, using highly variable markers, we examined the population genetics of the broadcast-spawning coral Acropora digitifera at 19 sites in seven regions along the 1,000 km long island chain of Nansei Islands, Japan. This area includes both subtropical and temperate habitats. Thus, the coral populations around the Nansei Islands in Japan are northern peripheral populations that would be subjected to environmental stresses different from those in tropical areas. The existence of high genetic connectivity across this large geographic area was suggested for all sites (FST≤0.033) although small but significant genetic differentiation was detected among populations in geographically close sites and regions. In addition, A. digitifera appears to be distributed throughout the Nansei Islands without losing genetic diversity. Therefore, A. digitifera populations in the Nansei Islands may be able to recover relatively rapidly even when high disturbances of coral communities occur locally if populations on other reefs are properly maintained

A multilocus assay reveals high nucleotide diversity and limited differentiation among Scandinavian willow grouse (Lagopus lagopus)

<p>Abstract</p> <p>Background</p> <p>There is so far very little data on autosomal nucleotide diversity in birds, except for data from the domesticated chicken and some passerines species. Estimates of nucleotide diversity reported so far in birds have been high (~10^-3) and a likely explanation for this is the generally higher effective population sizes compared to mammals. In this study, the level of nucleotide diversity has been examined in the willow grouse, a non-domesticated bird species from the order Galliformes, which also holds the chicken. The willow grouse (<it>Lagopus lagopus</it>) has an almost circumpolar distribution but is absent from Greenland and the north Atlantic islands. It primarily inhabits tundra, forest edge habitats and sub-alpine vegetation. Willow grouse are hunted throughout its range, and regionally it is a game bird of great cultural and economical importance.</p> <p>Results</p> <p>We sequenced 18 autosomal protein coding loci from approximately 15–18 individuals per population. We found a total of 127 SNP's, which corresponds to 1 SNP every 51 bp. 26 SNP's were amino acid replacement substitutions. Total nucleotide diversity (<it>π</it>_<it>t</it>) was between 1.30 × 10^-4and 7.66 × 10^-3(average <it>π</it>_{<it>t </it>}= 2.72 × 10^-3± 2.06 × 10^-3) and silent nucleotide diversity varied between 4.20 × 10^-4and 2.76 × 10^-2(average <it>π</it>_{<it>S </it>}= 9.22 × 10^-3± 7.43 × 10^-4). The synonymous diversity is approximately 20 times higher than in humans and two times higher than in chicken. Non-synonymous diversity was on average 18 times lower than the synonymous diversity and varied between 0 and 4.90 × 10^-3(average <it>π</it>_{<it>a </it>}= 5.08 × 10^-4± 7.43 × 10³), which suggest that purifying selection is strong in these genes. <it>F</it>_STvalues based on synonymous SNP's varied between -5.60 × 10^-4and 0.20 among loci and revealed low levels of differentiation among the four localities, with an overall value of <it>F</it>_ST= 0.03 (95% CI: 0.006 – 0.057) over 60 unlinked loci. Non-synonymous SNP's gave similar results. Low levels of linkage disequilibrium were observed within genes, with an average r²= 0.084 ± 0.110, which is expected for a large outbred population with no population differentiation. The mean per site per generation recombination parameter (ρ) was comparably high (0.028 ± 0.018), indicating high recombination rates in these genes.</p> <p>Conclusion</p> <p>We found unusually high levels of nucleotide diversity in the Scandinavian willow grouse as well as very little population structure among localities with up to 1647 km distance. There are also low levels of linkage disequilibrium within the genes and the population recombination rate is high, which is indicative of an old panmictic population, where recombination has had time to break up any haplotype blocks. The non-synonymous nucleotide diversity is low compared with the silent, which is in agreement with effective purifying selection, possibly due to the large effective population size.</p

Pelvic trauma : WSES classification and guidelines

Complex pelvic injuries are among the most dangerous and deadly trauma related lesions. Different classification systems exist, some are based on the mechanism of injury, some on anatomic patterns and some are focusing on the resulting instability requiring operative fixation. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic impairment of pelvic ring function and the associated injuries. The management of pelvic trauma patients aims definitively to restore the homeostasis and the normal physiopathology associated to the mechanical stability of the pelvic ring. Thus the management of pelvic trauma must be multidisciplinary and should be ultimately based on the physiology of the patient and the anatomy of the injury. This paper presents the World Society of Emergency Surgery (WSES) classification of pelvic trauma and the management Guidelines.Peer reviewe

Apolipoprotein A-II Influences Apolipoprotein E-Linked Cardiovascular Disease Risk in Women with High Levels of HDL Cholesterol and C-Reactive Protein

Background: In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C). To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups. Methodology/Principal: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II). Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles) revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036). Furthermore, high LpA-I: A-II levels interacted with high apoE levels in establishing subgroup risk. Conclusions/Significance: We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP

Signalling plasticity and energy saving in a tropical bushcricket

Males of the tropical bushcricket Mecopoda elongata synchronize their acoustic advertisement signals (chirps) in interactions with other males. However, synchrony is not perfect and distinct leader and follower roles are often maintained. In entrainment experiments in which conspecific signals were presented at various rates, chirps displayed as follower showed notable signal plasticity. Follower chirps were shortened by reducing the number and duration of syllables, especially those of low and medium amplitude. The degree of shortening depended on the time delay between leader and follower signals and the sound level of the entraining stimulus. The same signal plasticity was evident in male duets, with the effect that the last syllables of highest amplitude overlapped more strongly. Respiratory measurements showed that solo singing males producing higher chirp rates suffered from higher metabolic costs compared to males singing at lower rates. In contrast, respiratory rate was rather constant during a synchronous entrainment to a conspecific signal repeated at various rates. This allowed males to maintain a steady duty cycle, associated with a constant metabolic rate. Results are discussed with respect to the preference for leader signals in females and the possible benefits males may gain by overlapping their follower signals in a chorus