The common genetic variant upstream of INSIG2 gene is not associated with obesity in Indian population

The high incidence of obesity has resulted in increased morbidity and mortality worldwide. Obesity, a common lifestyle disorder, is caused by multiple factors with heredity playing a strong causal role. Recently, a genetic variation upstream of insulin-induced gene 2 (INSIG2) (rs7566605) has been reported to be associated with obesity in four separate cohorts. Because the lifestyle and food preferences of a large proportion of Indian population differ from the rest of the world, we studied the impact of this polymorphism with body mass index (BMI). The study consisted of two cohorts--1577 healthy individuals from three major linguistic lineages in India and 610 coronary artery disease cases and controls. In the two cohorts studied, no significant association was observed between the polymorphism and BMI. However, frequency of homozygous variant genotype was higher in non-obese individuals as compared with obese individuals in both cohorts although the difference was marginally significant only in the case-control cohort under the assumption of a recessive model. Furthermore, regardless of age and sex, mean BMI did not vary with genotype under the assumptions of recessive model. Thus, in contrast to earlier reports, the variant upstream of INSIG2 is not a determinant of BMI in Indian population.     

Toxicity of Nickel on the Selected Species of Marine Diatoms and Copepods

Toxicity values for nickel on marine diatoms and copepods were derived based on bioassay tests. The 96 h IC₅₀ of nickel on diatoms, Odontella mobiliensis and Coscinodiscus centralis were 0.31?±?0.01 and 0.62?±?0.02 mg/L and LC₅₀ values on copepods, Oithona similis and Acartia danae were 2.78?±?0.14 and 2.34?±?0.32 mg/L, respectively. The species mean chronic values of nickel were 0.016, 0.17, 0.57 and 0.42 mg/L for O. mobiliensis, C. centralis, O. similis and A. danae, respectively. A hazardous concentration was derived and evaluated using the species sensitivity distribution (SSD) method. SSD indicated that 13 µg Ni/L is the maximum allowable concentration for protection of 95% plankton species in coastal and marine ecosystem of India. Diatoms are more sensitive to nickel than copepods by almost an order of magnitude. The toxicity values derived in the present study may be useful to calculate ambient water quality criteria/standard for nickel.     

Strength and duration of GIPC-dependent signaling networks as determinants in cancer

GIPC is a PDZ-domain containing adaptor protein that regulates the cell surface expression and endocytic trafficking of numerous transmembrane receptors and signaling complexes. Interactions with over 50 proteins have been reported to date including VEGFR, insulin-like growth factor-1 receptor (IGF-1R), GPCRs, and APPL, many of which have essential roles in neuronal and cardiovascular development. In cancer, a major subset of GIPC-binding receptors and cytoplasmic effectors have been shown to promote tumorigenesis or metastatic progression, while other subsets have demonstrated strong tumor-suppressive effects. Given that these diverse pathways are widespread in normal tissues and human malignancies, precisely how these opposing signals are integrated and regulated within the same tumor setting likely depend on the strength and duration of their interactions with GIPC. This review highlights the major pathways and divergent mechanisms of GIPC signaling in various cancers and provide a rationale for emerging GIPC-targeted cancer therapies.     

Role of microRNAs in kidney homeostasis and disease

MicroRNAs (miRNAs) are endogenous short (20-22 nucleotides) non-coding RNA molecules that mediate gene expression. This is an important regulatory mechanism to modulate fundamental cellular processes such as differentiation, proliferation, death, metabolism, and pathophysiology of many diseases. The miRNA expression profile of the kidney differs greatly from that of other organs, as well as between the different regions in the kidney. In kidneys, miRNAs are indispensable for development and homeostasis. In this review, we explore the involvement of miRNAs in the regulation of blood pressure, hormone, water, and ion balance pertaining to kidney homeostasis. We also highlight their importance in renal pathophysiology, such as in polycystic disease, diabetic nephropathy, nephrogenic diabetes insipidus, hypertension, renal cancer, and kidney fibrosis (epithelial-mesenchymal transition). In addition, we highlight the need for further investigations on miRNA-based studies in the development of diagnostic, prognostic, and therapeutic tools for renal diseases.     

The well baby certificate for puerperal sterilization — A critical appraisal

From August 2004 to July 2005 at Coimbatore Medical College Hospital, Tamilnadu, the process of issuing well baby certificate to 1668 babies of 1658 mothers electing to undergo puerperal sterilization within a week of delivery was analyzed. 1553 babies (93.1%) were issued well baby certificates. Certificates were deferred in 88 babies (5.3%) and it was refused in 27 (1.6%). Reasons are analyzed and discussed.     

Experimental hypoxemic hypoxia: Changes in R2* of brain parenchyma accurately reflect the combined effects of changes in arterial and cerebral venous oxygen saturation

A two-dimensional T₂*-weighted gradient-echo sequence was used to image the rat brain before and during graded hypoxemia. Changes in R₂* (δR₂*) with respect to the control state were calculated for brain parenchyma and were compared with changes in hemoglobin saturation measured from both arterial and jugular venous blood samples. δR₂* was first correlated with the changes in arterial (δYa) and venous (δYv) hemoglobin saturations individually. Although a general trend toward a linear relationship with δR₂* was observed for both δYa and δYv, neither alone was strong (correlation coefficients r = 0.71 and 0.75 for δYa and δYv, respectively, and standard errors of the regression (SER) = 0.52 and 0.48 for δYa and δYv, respectively). However, when an “effective” cerebral blood hemoglobin saturation change (δYb) was constructed that takes into account the approximate weighting of the contributions from the arterial and venous phases of the circulation (δYb = 0.75 × δYv + 0.25 × δYa), a stronger correlation with δR₂* was obtained and there was less variance (r = 0.87 and SER = 0.35). It is concluded that an appropriate weighting of the contributions of arterial and venous phases of the circulation must be taken into account in modeling the volume susceptibility effects of deoxyhemoglobin on R₂* of brain parenchyma. In this way, a more accurate relationship between δR₂* and δYb can be obtained.     

Particulate air pollution from bushfires: human exposure and possible health effects

Toxicological studies have implicated trace metals adsorbed onto airborne particles as possible contributors to respiratory and/or cardiovascular inflammation. In particular, the water-soluble metal content is considered to be a harmful component of airborne particulate matter. In this work, the trace metal characteristics of airborne particulate matter, PM2.5, collected in Singapore from February to March 2005 were investigated with specific reference to their bioavailability. PM2.5 mass concentrations varied between 20.9 mug/m3 and 46.3 microg/m3 with an average mass of 32.8 microg/m3. During the sampling period, there were several bushfires in Singapore that contributed to sporadic increases in the particulate air pollution, accompanied by an acrid smell and asthma-related allergies. The aerosol samples were subjected to analysis of trace elements for determining their total concentrations as well as their water soluble fractions. Our results showed an increase in concentration of several water-soluble trace metals during bushfires compared to their urban background levels in Singapore. In order to measure the human exposure to particulate air pollution, the daily respiratory uptake (DRU) of several trace metals was calculated and compared between haze and nonhaze periods. The DRU values were significantly higher for several metals, including Zn, Cu, and Fe, during bushfires. Electron paramagnetic resonance (EPR) measurements showed that the particulate samples collected during bush fires generate more toxic hydroxyl radicals (OH.) than those in the background air, due to the presence of more soluble iron ions.