Association of adiponectin (AdipoQ) and sulphonylurea receptor (ABCC8) gene polymorphisms with Type 2 Diabetes in North Indian population of Punjab

In Type 2 Diabetes (T2D), adiponectin (AdipoQ) and sulphonylurea receptor genes (ABCC8) are important targets for candidate gene association studies. The single nucleotide polymorphisms (SNPs) in these genes have been associated with features of the metabolic syndrome across various populations. The present case–control study undertaken in the population of Punjab, evaluates the association of + 45T>G polymorphism in AdipoQ gene; and Exon16-3C>T as well as Exon18C>T polymorphisms in ABCC8 gene with T2D. These SNPs were genotyped in 200 T2D cases and 200 non-diabetic healthy controls using the PCR-RFLP method. The frequency of the minor G-allele for AdipoQ+ 45(T>G) polymorphism was significantly higher in T2D cases (29.0%) than in controls (21.5%) [P = 0.02, OR = 1.49 (1.07–2.04)]. The genetic model analysis revealed that the G-allele cumulatively provides nearly 1.59–1.78 fold increased risk to T2D under the additive (P = 0.009; OR = 1.59, 1.12–2.25 at 95% CI), dominant (TG/GG vs. TT) (P = 0.034, OR = 1.64, 1.04–2.56 at 95% CI) and codominant model (TG vs. TT/GG) (P = 0.014; OR = 1.78, 1.12–2.82 at 95% CI) after adjusting for confounding factors. However, no difference in the distribution of genotype and allele frequencies was observed for both the ABCC8 polymorphisms. The distribution of obesity profiles (BMI, WC and WHR) was also significantly different between cases and controls (P < 0.05). Higher BMI and central obesity were observed to increase the risk of T2D. G-allele of + 45(T>G) polymorphism in the adiponectin gene appears to be associated with increased risk of T2D, but the polymorphisms in sulphonylurea receptor gene do not seem to be associated with T2D in the population of Punjab.     

Mitochondrial DNA mutations in diabetes mellitus patients in Chinese Han population

Background and objective

Mutations of mitochondrial DNA are associated with diabetes mellitus (DM). The present case–control study aimed to investigate the mutations of mitochondrial DNA in DM patients of Chinese Han ethnicity.

Methods and results

A total of 770 DM patients and 309 healthy control individuals were enrolled. The mitochondrial DNA was extracted from blood cells and analyzed by the polymerase chain reaction–restriction fragment length polymorphism assay. In the diabetes group, there were 13 (1.69%) individuals carrying the mt3243 A → G mutation while none of the healthy control had this mutation. Though the 14709, 3316, 3394, and 12026 mutation variants were identified in 9, 17, 18 and 28 in DM patients respectively, there were no significant differences compared with control group. And the 3256, 8296, 8344, 8363, 3426 and 12258 mutations were not detected in either group. In the diabetes group, two double mutations were identified: A3243G+T3394C and A3243G+A12026G.

Conclusion

Our data suggested that mitochondrial gene tRNA^Leu(UUR) 3243 A → G mutation may be one risk of prevalence of DM and associated with worse clinical status in Chinese Han population.     

The impact of renin–angiotensin system,angiotensin І converting enzyme (insertion/deletion), and angiotensin ІІ type 1 receptor (A1166C) polymorphisms on breast cancer survival in Iran

Introduction

Several proteins of renin–angiotensin system (RAS) have been implicated in the process of growth promotion or inhibition of breast tissue and cancer cells. This study aimed to investigate the association between angiotensin I converting enzyme (ACE) insertion/deletion (I/D) and angiotensin receptor-1 (AGTR1) A1166C polymorphisms and survival of 110 women with breast cancer.

Materials and methods

The I/D and A1166C polymorphisms were evaluated by using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) in 110 breast cancer patients who had been treated between 2007 and 2009. Genomic DNA was extracted from a Formalin-Fixed Paraffin-Embedded (FFPE) tissue of breast cancer sample blocks. All the potential clinical and pathological prognostic variables were analyzed to establish the impact of I/D and A1166C polymorphisms on disease-free and overall survival rates. Disease-free and overall survival rates were the primary endpoints of the study.

Results

The ACE (I/D) polymorphism was associated with 3-year disease-free survival. Disease-free survival in DD carriers was significantly increased compared to ID plus II carriers (HR = 4.75; 95% CI, 1.39–16.24; p = 0.013). No significant association was found between AGTR1 (A1166C) and 3-year disease-free survival (p = 0.233). Also, the ACE (I/D) and AGTR1 (A1166C) polymorphisms were not associated with breast cancer overall survival.

Conclusion

The ACE (I/D) polymorphism was associated with 3-year disease-free survival of the women with breast cancer. Besides, disease-free survival in DD carriers was significantly increased compared to ID plus II carriers.     

Some observations of two kinds of lemuridae (Varecia variegata variegata andLemur fulvus albifrons) in the reserve of Nosy Mangabe

A total of nine groups of ruffed lemurs (Varecia variegata variegata), as well as one solitary individual, were observed on Nosy Mangabe, an island located off the eastern coast of Madagascar, for a total 536 min between November 30 and December 8, 1983. The average group size was 2.8 animals (N=5), and the population density was 175 animals/km², as estimated from direct observation and location of vocalization. During the same period, nine groups of brown lemurs (Lemur fulvus albifrons) and one solitary individual were observed for a total 320 min. One group of brown lemurs was composed of eight animals (two adult males and females, one male juvenile, two infants, and one individual of undetermined age and sex). Feeding competition occurred between the two species, with whichVarecia variegata variegata dominating.     

Fetal testosterone and empathy

BACKGROUND: In animals, fetal testosterone (fT) plays a central role in organizing the brain and in later social behavior. In humans, exposure to atypical levels of prenatal androgens may result in masculine behavior and ability patterns. Normal inter-individual variation in fT levels has also been correlated with later sex-typed behavior. METHODS: In the current study, 38 children (24 male, 14 female), whose fT was analyzed in amniotic fluid, were followed up at age 4. They were asked to describe cartoons with 2 moving triangles whose interactions with each other suggested social relationships and psychological motivations. RESULTS: Females used more mental and affective state terms to describe the cartoons than males. fT was not associated with the frequency of mental or affective state terms. Females also used more intentional propositions than males. fT was negatively correlated with the frequency of intentional propositions, taking sex differences into account. fT was also negatively correlated with the frequency of intentional propositions when males were examined separately. Males used more neutral propositions than females. fT was directly correlated with the frequency of neutral propositions, taking sex differences into account. This relationship was not seen when males and females were examined separately. CONCLUSIONS: These findings implicate fT in human social development. The relevance of our findings to the 'extreme male brain' theory of autism is also discussed.     

Population divergence in plasticity of the AVT system and its association with aggressive behaviors in a Death Valley pupfish

Behavioral differences can evolve rapidly in allopatry, but little is known about the neural bases of such changes. Allopatric populations of Amargosa pupfish (Cyprinodon nevadensis) vary in aggression and courtship behaviors in the wild. Two of these wild populations were recently found to differ in brain expression of arginine vasotocin (AVT)--a peptide hormone shown previously to modulate aggression in pupfish. These populations have been isolated for less than 4000 years, so it remained unclear whether the differences in behavior and neural AVT phenotype were evolved changes or plastic responses to ecologically dissimilar habitats. Here, I tested whether these population differences have a genetic basis by examining how aggressive behavior and neural AVT phenotype responded to ecologically relevant variation in salinity (0.4 ppt or 3 ppt) and temperature (stable or daily fluctuating). Pupfish from Big Spring were more aggressive than pupfish from the Amargosa River when bred and reared under common laboratory conditions. Morphometric analysis of preoptic AVT immunoreactivity showed that the populations differed in how the AVT system responded to salinity and temperature conditions, and revealed that this plasticity differed between parvocellular and magnocellular AVT neuron groups. Both populations also showed relationships between neural AVT phenotype and aggression in the rearing environment, although populations differed in how aggression related to variation in magnocellular AVT neuron size. Together, these results demonstrate that the pupfish populations have diverged in how physical and social conditions affect the AVT system, and provide evidence that the AVT system can evolve quickly to ecologically dissimilar environments.     

Conditioning properties of social subordination in rats: behavioral and biochemical correlates of anxiety

To develop a socially based model of anxiety, the contextual fear conditioning properties of social defeat were examined in rats. Social threat consisted of exposing intruders to aggressive residents in resident home cage, separated by a partition. During 3 daily encounters, intruders were either defeated or threatened by residents, providing the defeated-threatened (DT) and threatened-threatened (TT) groups respectively. On Day 4, both DT and TT animals were subjected to a social threat only. Additional animals received a 4-day exposure to a novel empty cage (EC group). Further DT, TT, and EC rats were confronted to a different context on Day 4. DT rats exhibited a robust and context-specific anxiety-like response, characterized by significant behavioral and biochemical alterations. DT rats showed increased risk assessment and decreased exploration compared to TT and EC rats that in turn were not different towards each other. DT and TT rats exhibited increased ACTH levels, while only DT rats showed enhanced corticosterone and decreased testosterone levels compared to EC. These differences were context-specific since they were absent confronting animals to a different context and since they were not long lasting. Overall, these data demonstrate the induction of an anxiety-like state in rats through a context conditioning process based upon social factors. The social basis of this paradigm offers good face validity with anxiety disorders, which in humans are mainly related to social factors and associated with HPA axis deregulations. The present procedure may provide a useful experimental model to further investigate the neurobiological mechanisms underlying anxiety-related disorders.     

Sex steroids modulate changes in social and sexual preference during juvenile development in zebra finches

Zebra finches, like many other animals, have close social relationships mainly with the family at young ages but begin to express interest in opposite-sex extra-family animals as they enter the late juvenile period and sexual maturity. This experiment tested a set of hypotheses that sex steroids are involved in this developmental transition. At 25-30 days, subjects were implanted subcutaneously with Silastic tubes that were empty (controls), filled with testosterone propionate, filled with estradiol benzoate, or filled with a combination of ATD (an aromatization inhibitor) and flutamide (an anti-androgen). Once a week between ages 30 and 90 days, they were given three-choice tests where the three stimulus types were the family members, unpaired males, or unpaired females. The preferred category was defined as the one adjacent to the proximity zone in which the subject spent the most time. Control males were more likely to prefer females and less likely to prefer the family as they got older, and control females were increasingly likely to prefer males. Males treated with testosterone or estradiol showed a premature increase in preferences for females. Females treated with ATD plus flutamide failed to show the normal increase in preferences for males shown by controls. These results indicate an involvement of sex steroids in the maturation of sexual preferences in a socially monogamous species that relies on visual and auditory, rather than olfactory, cues for sexual or other social behavior.     

Programming the offspring of the pig by prenatal social stress: neuroendocrine activity and behaviour

This study provides evidence in the pig that stress experienced during gestation has long-lasting effects on offspring daughters, including their maternal behaviour. Thirty-six primiparous sows were divided into control and two groups that were stressed (by social mixing) during either the second (Mix 2) or third (Mix 3) trimester of pregnancy. We found detrimental effects of mixing on the mothers' growth, body lesions, and cortisol secretion, but did not observe any significant effects on reproductive parameters including birth weight. At 60 days of age, 48 daughters were randomly selected from the three treatments: half were challenged using a restraint and isolation test. Then, all were culled and brain tissue was collected. In situ hybridisation measurements showed increased expression of CRH mRNA in the PVN in unrestrained Mix 2 and in the amygdala of Mix 2 and Mix 3 daughters. At 67 days, 24 further daughters were mixed to measure their responses to this social stress. All showed increased salivary cortisol secretion, but Mix 2 and Mix 3 daughters showed a greater and longer response than controls. Finally, all 24 were inseminated and at parturition maternal behaviour was measured. Mix 2 and Mix 3 daughters were more restless and more responsive to piglets that approached the head of the sow, traits which previously have been shown to be a component of abnormal maternal behaviour. Indeed, Mix 2 and Mix 3 daughters also tended to bite at their piglets more than control daughters.     

Elevated testosterone levels and social ranks in female rock hyrax

In mammals, males maintain significantly higher testosterone (T, 'the male hormone') levels than females throughout the year and are typically dominant over females. Our study of the cooperatively breeding rock hyrax (Procavia capensis) demonstrated a distinct exception. In most hyrax social groups that we studied, adult females were at the highest social rank within the group and showed higher than or equal T levels to males. To our knowledge, this is the first reported instance of adult female mammals demonstrating higher T levels than adult males. However, although T levels significantly correlated with rank in males, in females such correlations were not detected, suggesting a more complex interplay between behavior and endocrine factors in this species.