Macrophage Phenotypes and Gene Expression Patterns Are Unique in Naturally Occurring Metabolically Healthy Obesity.

Obesity impacts 650 million individuals globally, often co-occurring with metabolic syndrome. Though many obese individuals experience metabolic abnormalities (metabolically unhealthy obese [MUO]), ~30% do not (metabolically healthy obese [MHO]). Conversely, >10% of lean individuals are metabolically unhealthy (MUL).

Randomized Controlled Trial of a MUFA or Fiber-Rich Diet on Hepatic Fat in Prediabetes.

Context: Increased prevalence of type 2 diabetes mellitus and prediabetes worldwide is attributed in part to an unhealthy diet.

Objective: To evaluate whether 12 weeks of high monounsaturated fatty acid (MUFA) or fiber-rich weight-maintenance diet lowers hepatic fat and improves glucose tolerance in people with prediabetes.

Design: Subjects underwent a [6, 6-2H2]-labeled 75-g oral glucose tolerance test to estimate hepatic insulin sensitivity and liver fat fraction (LFF) using magnetic resonance spectroscopy before and after intervention.

Integrative network analysis reveals different pathophysiological mechanisms of insulin resistance among Caucasians and African Americans.

Background: African Americans (AA) have more pronounced insulin resistance and higher insulin secretion than European Americans (Caucasians or CA) when matched for age, gender, and body mass index (BMI). We hypothesize that physiological differences (including insulin sensitivity [SI]) between CAs and AAs can be explained by co-regulated gene networks in tissues involved in glucose homeostasis.

Methods: We performed integrative gene network analyses of transcriptomic data in subcutaneous adipose tissue of 99 CA and 37 AA subjects metabolically characterized as non-diabetic, with a range of SI and BMI values.

Expression quantitative trait analyses to identify causal genetic variants for type 2 diabetes susceptibility.

Type 2 diabetes (T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex heterogeneous metabolic phenotype in different ethnic and racial groups remains challenging. Despite recent success, the functional role of the T2D susceptibility variants implicated by genome-wide association studies (GWAS) remains largely unknown.

Genome-wide analyses of recombination prone regions predict role of DNA structural motif in recombination.

HapMap findings reveal surprisingly asymmetric distribution of recombinogenic regions. Short recombinogenic regions (hotspots) are interspersed between large relatively non-recombinogenic regions. This raises the interesting possibility of DNA sequence and/or other cis- elements as determinants of recombination.

Effect of addition of pond ash and fly ash on properties of ash-clay burnt bricks.

Two industrial solid waste products generated by Indian coal-fired power plants, namely pond ash and fly ash, were used in combination with local clay to develop building bricks. The clay were mixed with the two different ashes in the range 10 to 90 wt.%, hydraulically pressed and fired at 1000 degrees C.

The search for type 2 diabetes susceptibility loci: the chromosome 1q story.

The unbiased approach of genome-wide linkage analysis has shown evidence for linkage of type 2 diabetes mellitus to the chromosome 1q21-25 region in at least eight independent studies. More than 26 candidate genes have already been evaluated, but to date none explain the evidence for linkage in this gene-dense region. Considerable data suggest that multiple genes account for this linkage result.

Activating transcription factor 6 (ATF6) sequence polymorphisms in type 2 diabetes and pre-diabetic traits.

Activating transcription factor 6 (ATF6) is located within the region of linkage to type 2 diabetes on chromosome 1q21-q23 and is a key activator of the endoplasmic reticulum stress response. We evaluated 78 single nucleotide polymorphisms (SNPs) spanning >213 kb in 95 people, from which we selected 64 SNPs for evaluation in 191 Caucasian case subjects from Utah and between 165 and 188 control subjects. Six SNPs showed nominal associations with type 2 diabetes (P = 0.

Polymorphisms in the glucokinase-associated, dual-specificity phosphatase 12 (DUSP12) gene under chromosome 1q21 linkage peak are associated with type 2 diabetes.

Linkage of type 2 diabetes to chromosome 1q21-q23 is well replicated across populations. In an initial 50-kb marker map (580 markers) across the linked region, one of the two strongest associations observed in Utah Caucasians was at marker rs1503814 (P < 0.00001 in pools, P < 0.

The Genetic Basis of Type 2 Diabetes.

Type 2 Diabetes results from a complex physiologic process that includes the pancreatic beta cells, peripheral glucose uptake in muscle, the secretion of multiple cytokines and hormone-like molecules from adipocytes, hepatic glucose production, and likely the central nervous system. Consistent with the complex web of physiologic defects, the emerging picture of the genetics will involve a large number of risk susceptibility genes, each individually with relatively small effect (odds ratios below 1.2 in most cases).

Genome-wide prediction of G4 DNA as regulatory motifs: role in Escherichia coli global regulation.

The role of nonlinear DNA in replication, recombination, and transcription has become evident in recent years. Although several studies have predicted and characterized regulatory elements at the sequence level, very few have investigated DNA structure as regulatory motifs. Here, using G-quadruplex or G4 DNA motifs as a model, we have researched the role of DNA structure in transcription on a genome-wide scale.

SYNGR1 is associated with schizophrenia and bipolar disorder in southern India.

Chromosome 22q11-13 is one of the most consistent linkage regions for schizophrenia (SCZ) and bipolar disorder (BPAD). The SYNGR1 gene, which is associated with presynaptic vesicles in neuronal cells, is located on 22q13.1.

Detection of differential gene copy number using denaturing high performance liquid chromatography.

Genomic rearrangements leading to deletion or duplication of gene(s) resulting in alterations in gene copy number underlie the molecular lesion in several genetic disorders. Methods currently used to determine gene copy number including real time PCR, southern hybridization, fluorescence in situ hybridization, densitometric scanning of PCR product etc. have certain disadvantages and are also expensive and time consuming.

MLC1 gene is associated with schizophrenia and bipolar disorder in Southern India.

Background: Chromosome 22q13 has shown linkage with schizophrenia (SCZ) and bipolar affective disorder (BPAD). A missense mutation in MLC1 (putative cation-channel gene on 22q13) co-segregating with periodic catatonic schizophrenia has been reported. We have investigated the relationship of MLC1 with SCZ and BPAD in Southern India.

Calsquestrin 1 (CASQ1) gene polymorphisms under chromosome 1q21 linkage peak are associated with type 2 diabetes in Northern European Caucasians.

Genome-wide scans in multiple populations have identified chromosome 1q21-q24 as one susceptibility region for type 2 diabetes. To map the susceptibility genes, we first placed a dense single nucleotide polymorphism (SNP) map across the linked region. We identified two SNPs that showed strong associations, and both mapped to within intron 2 of the calsequestrin 1 (CASQ1) gene.

Linkage and association mapping of a chromosome 1q21-q24 type 2 diabetes susceptibility locus in northern European Caucasians.

We have identified a region on chromosome 1q21-q24 that was significantly linked to type 2 diabetes in multiplex families of Northern European ancestry and also in Pima Indians, Amish families, and families from France and England. We sought to narrow and map this locus using a combination of linkage and association approaches by typing microsatellite markers at 1.2 and 0.

Induction of micronuclei by zinc in human leukocytes: a study using cytokinesis-block micronucleus assay.

In the present study, we report the results of the capability of zinc chloride for the induction of micronuclei in cultured human leukocytes using cytokinesis-block micronucleus assay. Two concentrations of zinc chloride (1.5 x 10(-4) M and 3.

Interaction of different hemoglobinopathies in Eastern India with a view to establish genotype-phenotype correlation.

Analysis of the molecular basis of hemoglobinopathies provides an opportunity to define genotype-phenotype variations as well as establish the origin of mutation. The present study deals with a large cohort of 1,661 cases referred to the counseling unit and 889 individuals from random screening of the population of Tripura. Characterization of mutation in 291 cases (582 alleles) was performed by the PCR-ARMS method using genomic DNA.