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1.  Identification of a KIR antisense lncRNA expressed by progenitor cells 
Genes and immunity  2013;14(7):10.1038/gene.2013.36.
Human NK cells express cell surface class I MHC receptors (KIR) in a probabilistic manner. Previous studies have shown that a distal promoter acts in conjunction with a proximal bidirectional promoter to control the selective activation of KIR genes. We report here the presence of an intron 2 promoter in several KIR genes that produces a spliced antisense transcript. This lncRNA transcript contains antisense sequence complementary to KIR-coding exons 1 and 2 as well as the proximal promoter region of the KIR genes. The antisense promoter contains MZF-1 binding sites, a transcription factor found in hematopoietic progenitors and myeloid precursors. The KIR antisense lncRNA was only detected in progenitor cells or pluripotent cell lines, suggesting a function that is specific for stem cells. Overexpression of MZF-1 in developing NK cells led to decreased KIR expression, consistent with a role for the KIR antisense lncRNA in silencing KIR gene expression early in development.
doi:10.1038/gene.2013.36
PMCID: PMC3808466  PMID: 23863987
human; NK cells; KIR; antisense; transcription; lncRNA
2.  Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene 
Nature genetics  2013;45(10):10.1038/ng.2745.
Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation to clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have empirical evidence that they cause cystic fibrosis. To address this gap, we collected both genotype and phenotype data for 39,696 cystic fibrosis patients in registries and clinics in North America and Europe. Among these patients, 159 CFTR variants had an allele frequency of ≥0.01%. These variants were evaluated for both clinical severity and functional consequence with 127 (80%) meeting both clinical and functional criteria consistent with disease. Assessment of disease penetrance in 2,188 fathers of cystic fibrosis patients enabled assignment of 12 of the remaining 32 variants as neutral while the other 20 variants remained indeterminate. This study illustrates that sourcing data directly from well-phenotyped subjects can address the gap in our ability to interpret clinically-relevant genomic variation.
doi:10.1038/ng.2745
PMCID: PMC3874936  PMID: 23974870
3.  Microtubule modifications and stability are altered by cilia perturbation and in cystic kidney disease 
Cytoskeleton (Hoboken, N.J.)  2012;70(1):24-31.
Summary
Disruption of the primary cilium is associated with a growing number of human diseases collectively termed ciliopathies. Ciliopathies present with a broad range of clinical features consistent with the near ubiquitous nature of the organelle and its role in diverse signaling pathways throughout development and adult homeostasis. The clinical features associated with cilia dysfunction can include such phenotypes as polycystic kidneys, skeletal abnormalities, blindness, anosmia, and obesity. Although the clinical relevance of the primary cilium is evident, the effects that cilia dysfunction has on the cell and how this contributes to disease remains poorly understood. Here, we show that loss of ciliogenesis genes such as Ift88 and Kif3a lead to increases in post-translational modifications on cytosolic microtubules. This effect was observed in cilia mutant kidney cells grown in vitro and in vivo in cystic kidneys. The hyper-acetylation of microtubules resulting from cilia loss is associated with both altered microtubule stability and increased α-tubulin acetyl-transferase activity. Intriguingly, the effect on microtubules was also evident in renal samples from patients with autosomal recessive polycystic kidneys. These findings indicate that altered microtubule post-translational modifications may influence some of the phenotypes observed in ciliopathies.
doi:10.1002/cm.21088
PMCID: PMC3552319  PMID: 23124988
cilia; tubulin; acetylation; microtubules; Polycystic Kidney Disease
4.  Correction: Phospholipid Biosynthesis Genes and Susceptibility to Obesity: Analysis of Expression and Polymorphisms 
PLoS ONE  2013;8(12):10.1371/annotation/7b3edc45-39c7-416b-a7dc-124f4846303d.
doi:10.1371/annotation/7b3edc45-39c7-416b-a7dc-124f4846303d
PMCID: PMC3861939
5.  Multidisciplinary Approach to the Rehabilitation in Management of Child with Early Childhood Caries: A Case Report 
The aesthetic requirement of severely mutilated primary anterior teeth in case of Early Childhood Caries (ECC) has been a challenge to paediatric dentists. ECC involves the upper anterior teeth early in life and by the time the dentist sees the child, most of the coronal structure is lost. This article presents the clinical sequence of rehabilitation of maxillary anterior primary teeth, and the mandibular posterior teeth.
doi:10.7860/JCDR/2013/5272.3528
PMCID: PMC3843449  PMID: 24298533
Early childhood caries; Aesthetics; Hybrid composite; Polyethylene fibre
6.  Improved insulin sensitivity after treatment of PPARγ and PPARα ligands is mediated by genetically modulated transcripts 
Pharmacogenetics and Genomics  2012;22(7):484-497.
Objectives
We aimed to define effects of PPARγ and PPARα agonist mono and combination therapy on adipose tissue and skeletal muscle gene expression in relation to insulin sensitivity. We further investigated the role of genetic polymorphisms in PPAR ligand-modulated genes in transcriptional regulation and glucose homeostasis.
Methods
Genome-wide transcript profiles of subcutaneous adipose and skeletal muscle and metabolic phenotypes were determined before and after 10 weeks of pioglitazone and fenofibrate mono or combination therapy in 26 subjects with impaired glucose tolerance. To establish the functional role of SNPs in genes modulated by pioglitazone alone or in combination with fenofibrate, we interrogated genome-wide association data of continuous glycemic phenotypes from the MAGIC study and adipose eQTL data from the MuTHER study.
Results
PPARγ, alone or in combination with PPARα agonists, mediated up-regulation of genes involved in the TCA cycle, branched chain amino acid metabolism, fatty acid metabolism, PPAR signaling, AMPK and cAMP signaling, and insulin signaling pathways, and downregulation of genes in antigen processing and presentation, immune and inflammatory response in adipose tissue. Remarkably few changes were found in muscle. Strong enrichment of genes involved in propanoate metabolism, fatty acid elongation in mitochondria, and acetyl-CoA metabolic process were observed only in adipose tissue of the combined pioglitazone and fenofibrate treatment group. After interrogating MAGIC data, SNPs in 22 genes modulated by PPAR ligands were associated with fasting plasma glucose and the expression of 28 transcripts modulated by PPAR ligands was under control of local genetic regulators (cis-eQTLs) in adipose tissue of MuTHER study twins.
Conclusions
We found differences in transcriptional mechanisms that may describe insulin sensitizing effects of PPARγ agonist monotherapy or in combination with PPARα agonist. The regulatory and glucose homeostasis trait-associated SNPs in PPAR agonist-modulated genes are important candidates for future studies that may explain the inter-individual variability in response to thiazolidinedione and fenofibrate treatment.
doi:10.1097/FPC.0b013e328352a72e
PMCID: PMC3376224  PMID: 22437669
insulin resistance; gene expression profile; muscle; adipose; pioglitazone; fenofibrate; eQTL
7.  Phospholipid Biosynthesis Genes and Susceptibility to Obesity: Analysis of Expression and Polymorphisms 
PLoS ONE  2013;8(5):e65303.
Recent studies have identified links between phospholipid composition and altered cellular functions in animal models of obesity, but the involvement of phospholipid biosynthesis genes in human obesity are not well understood. We analyzed the transcript of four phospholipid biosynthesis genes in adipose and muscle from 170 subjects. We examined publicly available genome-wide association data from the GIANT and MAGIC cohorts to investigate the association of SNPs in these genes with obesity and glucose homeostasis traits, respectively. Trait-associated SNPs were genotyped to evaluate their roles in regulating expression in adipose. In adipose tissue, expression of PEMT, PCYT1A, and PTDSS2 were positively correlated and PCYT2 was negatively correlated with percent fat mass and body mass index (BMI). Among the polymorphisms in these genes, SNP rs4646404 in PEMT showed the strongest association (p = 3.07E-06) with waist-to-hip ratio (WHR) adjusted for BMI. The WHR-associated intronic SNP rs4646343 in the PEMT gene showed the strongest association with its expression in adipose. Allele “C” of this SNP was associated with higher WHR (p = 2.47E-05) and with higher expression (p = 4.10E-04). Our study shows that the expression of PEMT gene is high in obese insulin-resistant subjects. Intronic cis-regulatory polymorphisms may increase the genetic risk of obesity by modulating PEMT expression.
doi:10.1371/journal.pone.0065303
PMCID: PMC3665552  PMID: 23724137
8.  An ACACB Variant Implicated in Diabetic Nephropathy Associates with Body Mass Index and Gene Expression in Obese Subjects 
PLoS ONE  2013;8(2):e56193.
Acetyl coenzyme A carboxylase B gene (ACACB) single nucleotide polymorphism (SNP) rs2268388 is reproducibly associated with type 2 diabetes (T2DM)-associated nephropathy (DN). ACACB knock-out mice are also protected from obesity. This study assessed relationships between rs2268388, body mass index (BMI) and gene expression in multiple populations, with and without T2DM. Among subjects without T2DM, rs2268388 DN risk allele (T) associated with higher BMI in Pima Indian children (n = 2021; p-additive = 0.029) and African Americans (AAs) (n = 177; p-additive = 0.05), with a trend in European Americans (EAs) (n = 512; p-additive = 0.09), but not Germans (n = 858; p-additive = 0.765). Association with BMI was seen in a meta-analysis including all non-T2DM subjects (n = 3568; p-additive = 0.02). Among subjects with T2DM, rs2268388 was not associated with BMI in Japanese (n = 2912) or EAs (n = 1149); however, the T allele associated with higher BMI in the subset with BMI≥30 kg/m2 (n = 568 EAs; p-additive = 0.049, n = 196 Japanese; p-additive = 0.049). Association with BMI was strengthened in a T2DM meta-analysis that included an additional 756 AAs (p-additive = 0.080) and 48 Hong Kong Chinese (p-additive = 0.81) with BMI≥30 kg/m2 (n = 1575; p-additive = 0.0033). The effect of rs2268388 on gene expression revealed that the T risk allele associated with higher ACACB messenger levels in adipose tissue (41 EAs and 20 AAs with BMI>30 kg/m2; p-additive = 0.018) and ACACB protein levels in the liver tissue (mixed model p-additive = 0.03, in 25 EA bariatric surgery patients with BMI>30 kg/m2 for 75 exams). The T allele also associated with higher hepatic triglyceride levels. These data support a role for ACACB in obesity and potential roles for altered lipid metabolism in susceptibility to DN.
doi:10.1371/journal.pone.0056193
PMCID: PMC3584087  PMID: 23460794
9.  Prevalence of metabolic syndrome in adolescents aged 10-18 years in Jammu, J and K 
Objective:
To estimate the prevalence of metabolic syndrome among adolescents attending school in the Jammu region, India.
Materials and Methods:
This is a cross-sectional study conducted between November 2009 and December 2010, among a total of 1160 school-going adolescents of both sexes aged 10-18 years. Relevant metabolic and anthropometric variables were analyzed and criteria suggested by National Cholesterol Education Program Adult Treatment Panel Third (NCEP-ATP III) modified forage was used to define metabolic syndrome.
Results:
The overall prevalence of metabolic syndrome was 2.6%. Prevalence of metabolic syndrome was higher in males (3.84%) than in females (1.6%) and slightly higher in urban area (2.80%) than in rural area (2.52%), whereas prevalence of metabolic syndrome among centrally obese subjects was as high as 33.33%. High density lipoprotein cholesterol was the most common and high blood pressure was the least common constituent of metabolic syndrome. Metabolic syndrome was most prevalent in 16-18 years age group (4.79%).
Conclusion:
This study demonstrates that metabolic syndrome phenotype exists in substantial number (up to 3%) of adolescent population in the Jammu region, India, and particularly 33% of obese adolescents are at risk to develop metabolic syndrome. These findings pose a serious threat to the current and future health of these young people.
doi:10.4103/2230-8210.107849
PMCID: PMC3659880  PMID: 23776866
Adolescents; metabolic syndrome; obesity; prevalence
10.  KIR Antisense Transcripts are Processed into a 28 Base PIWI-like RNA in Human NK Cells 
Killer immunoglobulin-like receptors (KIR) are expressed in a variegated, clonally restricted fashion on natural killer (NK) cells and are important determinants of NK cell function. Although silencing of individual KIR genes is strongly correlated with the presence of CpG dinucleotide methylation within the promoter, the mechanism responsible for silencing has not been identified. Our results show that antisense transcripts mediate KIR transcriptional silencing through a novel PIWI-like 28 base small RNA. Although PIWI RNA-mediated silencing of transposable elements within germ cells have been described, this is the first report that identifies a PIWI-like RNA in an immune somatic cell lineage and identifies a mechanism which may be broadly used in orchestrating immune development.
doi:10.4049/jimmunol.1000855
PMCID: PMC3477858  PMID: 20631304
11.  Primary Oral Malignant Melanoma: Two Case Reports and Review of Literature 
Case Reports in Dentistry  2012;2012:975358.
Primary malignant melanoma of the oral cavity is a rare neoplasm. The tumors tend to metastasize or locally invade tissue more readily than other malignant tumors in the oral region. The survival of patients with mucosal melanomas is less than for those with cutaneous melanomas. Tumor size and metastases are related to the prognosis of the disease. Early detection, therefore, is important.
doi:10.1155/2012/975358
PMCID: PMC3414006  PMID: 22900212
12.  Unusual Foreign Bodies in the Orofacial Region 
Case Reports in Dentistry  2012;2012:191873.
Foreign bodies may be deposited in the oral cavity either by traumatic injury or iatrogenically. Among the commonly encountered iatrogenic foreign bodies are restorative materials like amalgam, obturation materials, broken instruments, needles, and so forth. The discovery of foreign bodies in the teeth is a special situation, which is often diagnosed accidentally. Detailed case history, clinical and radiographic examinations are necessary to come to a conclusion about the nature, size, location of the foreign body, and the difficulty involved in its retrieval. It is more common to find this situation in children as it is a well-known fact that children often tend to have the habit of placing foreign objects in the mouth. Sometimes the foreign objects get stuck in the root canals of the teeth, which the children do not reveal to their parents due to fear. These foreign objects may act as a potential source of infection and may later lead to a painful condition. This paper discusses the presence of unusual foreign bodies—a tip of the metallic compass, stapler pin, copper strip, and a broken sewing needle impregnated in the gingiva and their management.
doi:10.1155/2012/191873
PMCID: PMC3399346  PMID: 22830058
13.  Single Nucleotide Polymorphisms in JAZF1 and BCL11A gene are nominally associated with Type 2 Diabetes in African American Families from the GENNID Study 
Journal of Human Genetics  2011;57(1):57-61.
Prior type 2 diabetes (T2D) genome-wide association studies (GWASs) have generated a list of well-replicated susceptibility loci in populations of European and Asian ancestry. In order to validate the trans-ethnic contribution of these GWAS SNPs, we performed a family-based association analysis of 32 selected GWAS SNPs in a cohort of 1496 African American (AA) subjects from the GENNID study. Functional roles of these SNPs were evaluated by screening cis-eQTLs in transformed lymphoblast cell lines available for a sub-group of GENNID families from Arkansas. Only three of the 32 GWAS-derived SNPs showed nominally significant association with T2D in our AA cohort. Among the replicated SNPs rs864745 in JAZF1 and rs10490072 in BCL11A gene (p= 0.006 and 0.03, respectively, after adjustment for BMI) were within the 1-lod drop support interval of T2D linkage peaks reported in these families. Genotyping of 19 Tag-SNPs in these two loci revealed no further common SNPs or haplotypes that may be a stronger predictor of T2D susceptibility than the index SNPs. Six T2D GWAS SNPs (rs6698181, rs9472138, rs730497, rs10811661, rs11037909, and rs1153188) were associated with nearby transcript expression in transformed lymphoblast cell lines of GENNID AA subjects. Thus, our study indicates a nominal role for JAZF1 and BCL11A variants in T2D susceptibility in AAs and suggested little overlap in known susceptibility to T2D between European and African derived populations when considering GWAS SNPs alone.
doi:10.1038/jhg.2011.133
PMCID: PMC3266455  PMID: 22113416
Association; Diabetes; eQTL; gene expression; linkage disequilibrium; SNP
14.  Adenomatoid odontogenic tumor: As an unusual mandibular manifestation 
Contemporary Clinical Dentistry  2012;3(Suppl1):S29-S32.
Adenomatoid odontogenic tumor (AOT) is a rare odontogenic tumor which is often misdiagnosed as odontogenic cyst and accounts for about 1% until 9% of all odontogenic tumors. It is predominantly found in young and female patients, located more often in the maxilla in most cases associated with an unerupted permanent tooth. It is a benign (hamartomatous), noninvasive lesion with slow but progressive growth. There are three variants of AOT: follicular, extrafollicular, and peripheral. We report a rare case of follicular-type AOT in the mandible of a 14-year-old male patient who presented with right -sided jaw swelling.
doi:10.4103/0976-237X.95100
PMCID: PMC3354808  PMID: 22629062
Adenomatoid odontogenic tumor; benign; hamartoma; odontogenic tumors
15.  Analysis of osteocalcin as a candidate gene for Type 2 Diabetes (T2D) and intermediate traits in Caucasians and African Americans 
Disease Markers  2010;28(5):281-286.
Recent studies in mice and human identified osteocalcin (OCN) as a bone-derived hormone that modulates insulin secretion and insulin sensitivity. OCN is synthesized by the bone gamma-carboxyglutamate protein (BGLAP) gene located in the well replicated region of type 2 diabetes (T2D) linkage on chromosome 1q22. We resequenced BGLAP gene in 192 individuals with T2D and performed case-control studies in 766 Caucasian (461 T2D and 305 controls) and 563 African American individuals (371 T2D and 192 controls). Metabolic effects of BGLAP variants were examined in 127 nondiabetic members of Caucasian T2D families and in 498 unrelated nondiabetic African American and Caucasian individuals. BGLAP expression was tested in transformed lymphocytes from 60 Caucasian individuals. We identified 17 single nucleotide polymorphisms (SNPs) in African Americans, but observed only the two known SNPs in Caucasians. No SNP was associated with T2D. Promoter SNP rs1800247 was not associated with metabolic traits including insulin sensitivity (SI) or fasting glucose in either population, but nonsynonymous SNP rs34702397 (R94Q) was nominally associated with SI (uncorrected p=0.05) and glucose-mediated glucose disposal (SG; uncorrected p=0.03) in African Americans. No SNP altered measures of insulin secretion or obesity, nor was BGLAP expression associated with rs1800247. Our study was sufficiently powered to exclude BGLAP variants as a major risk factor (OR>1.5) for T2D in Caucasians, but coding variants in exon 4 may alter glucose homeostasis and diabetes risk in African Americans.
doi:10.3233/DMA-2010-0701
PMCID: PMC3304587  PMID: 20592451
Osteocalcin; Diabetes; Polymorphism; Transcript; Association; Insulin sensitivity
16.  Global Gene Expression Profiles of Subcutaneous Adipose and Muscle From Glucose-Tolerant, Insulin-Sensitive, and Insulin-Resistant Individuals Matched for BMI 
Diabetes  2011;60(3):1019-1029.
OBJECTIVE
To determine altered gene expression profiles in subcutaneous adipose and skeletal muscle from nondiabetic, insulin-resistant individuals compared with insulin-sensitive individuals matched for BMI.
RESEARCH DESIGN AND METHODS
A total of 62 nondiabetic individuals were chosen for extremes of insulin sensitivity (31 insulin-resistant and 31 insulin-sensitive subjects; 40 were European American and 22 were African American) and matched for age and obesity measures. Global gene expression profiles were determined and compared between ethnic groups and between insulin-resistant and insulin-sensitive participants individually and using gene-set enrichment analysis.
RESULTS
African American and European American subjects differed in 58 muscle and 140 adipose genes, including many inflammatory and metabolically important genes. Peroxisome proliferator–activated receptor γ cofactor 1A (PPARGC1A) was 1.75-fold reduced with insulin resistance in muscle, and fatty acid and lipid metabolism and oxidoreductase activity also were downregulated. Unexpected categories included ubiquitination, citrullination, and protein degradation. In adipose, highly represented categories included lipid and fatty acid metabolism, insulin action, and cell-cycle regulation. Inflammatory genes were increased in European American subjects and were among the top Kyoto Encyclopedia of Genes and Genomes pathways on gene-set enrichment analysis. FADS1, VEGFA, PTPN3, KLF15, PER3, STEAP4, and AGTR1 were among genes expressed differentially in both adipose and muscle.
CONCLUSIONS
Adipose tissue gene expression showed more differences between insulin-resistant versus insulin-sensitive groups than the expression of genes in muscle. We confirm the role of PPARGC1A in muscle and show some support for inflammation in adipose from European American subjects but find prominent roles for lipid metabolism in insulin sensitivity independent of obesity in both tissues.
doi:10.2337/db10-1270
PMCID: PMC3046820  PMID: 21266331
17.  The Effect of ACACB cis-Variants on Gene Expression and Metabolic Traits 
PLoS ONE  2011;6(8):e23860.
Background
Acetyl Coenzyme A carboxylase β (ACACB) is the rate-limiting enzyme in fatty acid oxidation, and continuous fatty acid oxidation in Acacb knock-out mice increases insulin sensitivity. Systematic human studies have not been performed to evaluate whether ACACB variants regulate gene expression and insulin sensitivity in skeletal muscle and adipose tissues. We sought to determine whether ACACB transcribed variants were associated with ACACB gene expression and insulin sensitivity in non-diabetic African American (AA) and European American (EA) adults.
Methods
ACACB transcribed single nucleotide polymorphisms (SNPs) were genotyped in 105 EAs and 46 AAs whose body mass index (BMI), lipid profiles and ACACB gene expression in subcutaneous adipose and skeletal muscle had been measured. Allelic expression imbalance (AEI) was assessed in lymphoblast cell lines from heterozygous subjects in an additional EA sample (n = 95). Selected SNPs were further examined for association with insulin sensitivity in a cohort of 417 EAs and 153 AAs.
Results
ACACB transcribed SNP rs2075260 (A/G) was associated with adipose ACACB messenger RNA expression in EAs and AAs (p = 3.8×10−5, dominant model in meta-analysis, Stouffer method), with the (A) allele representing lower gene expression in adipose and higher insulin sensitivity in EAs (p = 0.04). In EAs, adipose ACACB expression was negatively associated with age and sex-adjusted BMI (r = −0.35, p = 0.0002).
Conclusions
Common variants within the ACACB locus appear to regulate adipose gene expression in humans. Body fat (represented by BMI) may further regulate adipose ACACB gene expression in the EA population.
doi:10.1371/journal.pone.0023860
PMCID: PMC3162605  PMID: 21887335
18.  Pulmonary hamartoma with tuberculosis masquerading as metastasis 
Annals of Thoracic Medicine  2011;6(3):152-153.
doi:10.4103/1817-1737.82452
PMCID: PMC3131760  PMID: 21760849
19.  Soluble levels of cytosolic tubulin regulate ciliary length control 
Molecular Biology of the Cell  2011;22(6):806-816.
We show that manipulation of either the microtubule or the actin cytoskeleton has unexpected influences on cilia length control.
The primary cilium is an evolutionarily conserved dynamic organelle important for regulating numerous signaling pathways, and, as such, mutations disrupting ciliogenesis result in a variety of developmental abnormalities and postnatal disorders. The length of the cilium is regulated by the cell through largely unknown mechanisms. Normal cilia length is important, as either shortened or elongated cilia have been associated with disease and developmental defects. Here we explore the importance of cytoskeletal dynamics in regulating cilia length. Using pharmacological approaches in different cell types, we demonstrate that actin depolymerization or stabilization and protein kinase A activation result in a rapid elongation of the primary cilium. The effects of pharmacological agents on cilia length are associated with a subsequent increase in soluble tubulin levels and can be impaired by depletion of soluble tubulin with taxol. In addition, subtle nocodazole treatment was able to induce ciliogenesis under conditions in which cilia are not normally formed and also increases cilia length on cells that have already established cilia. Together these data indicate that cilia length can be regulated through changes in either the actin or microtubule network and implicate a possible role for soluble tubulin levels in cilia length control.
doi:10.1091/mbc.E10-03-0269
PMCID: PMC3057705  PMID: 21270438
20.  Role of ADAM33 gene and associated single nucleotide polymorphisms in asthma 
Allergy & Rhinology  2011;2(2):e63-e70.
Asthma is a multifactorial disorder, primarily resulting from interactions between genetic and environmental factors. ADAM33 gene (located on chromosome 20p13) has been reported to play an important role in asthma. This review article is intended to include all of the publications, to date, which have assessed the association of ADAM33 gene polymorphisms as well as have shown the role of ADAM33 gene in airway remodeling and their expression with asthma. A PubMed search was performed for studies published between 1990 and 2010. The terms “ADAM33,” “ADAM33 gene and asthma,” and “ADAM33 gene polymorphisms” were used as search criteria. Based on available literature we can only speculate its role in the morphogenesis and functions of the lung. Fourteen studies conducted in different populations were found showing an association of ADAM33 gene polymorphisms with asthma. However, none of the single nucleotide polymorphisms (SNPs) of ADAM33 gene had found association with asthma across all ethnic groups. Because higher expression of ADAM33 is found in the fibroblast and smooth muscle cells of the lung, over- or underexpression of ADAM33 gene may result in alterations in airway remodeling and repair processes. However, no SNP of ADAM33 gene showed significant associations with asthma across all ethnic groups; the causative polymorphism, if any, still has to be identified.
doi:10.2500/ar.2011.2.0018
PMCID: PMC3390120  PMID: 22852121
ADAM33; airway remodeling; association studies; asthma; bronchial hyperresponsiveness; chronic inflammatory disorder; multifactorial disorder; pathogenesis of asthma; positional cloning; single-nucleotide polymorphism
21.  A single visit, reattachment of fractured crown fragment 
Contemporary Clinical Dentistry  2010;1(3):168-170.
“Minimal intervention with maximum dentistry” The immediate restorative technique resolving the acute problem of traumatic tooth fracture with pulpal involvement–An immediate fracture fragment reattachment using pre-fabricated fiber post with dual cure cement–A challenging, conservative, aesthetics, rehabilitating, functionally, and economically viable single visit procedure.
doi:10.4103/0976-237X.72785
PMCID: PMC3220104  PMID: 22114409
Fragment reattachment; pre-fabricated fiber post; tooth fracture
22.  Analysis of Osteocalcin as a Candidate Gene for Type 2 Diabetes (T2D) and Intermediate Traits in Caucasians and African Americans 
Disease markers  2010;28(5):281-286.
Recent studies in mice and human identified osteocalcin (OCN) as a bone-derived hormone that modulates insulin secretion and insulin sensitivity. OCN is synthesized by the bone gamma-carboxyglutamate protein (BGLAP) gene located in the well replicated region of type 2 diabetes (T2D) linkage on chromosome 1q22. We resequenced BGLAP gene in 192 individuals with T2D and performed case-control studies in 766 Caucasian (461 T2D and 305 controls) and 563 African American individuals (371 T2D and 192 controls). Metabolic effects of BGLAP variants were examined in 127 nondiabetic members of Caucasian T2D families and in 498 unrelated nondiabetic African American and Caucasian individuals. BGLAP expression was tested in transformed lymphocytes from 60 Caucasian individuals. We identified 17 single nucleotide polymorphisms (SNPs) in African Americans, but observed only the two known SNPs in Caucasians. No SNP was associated with T2D. Promoter SNP rs1800247 was not associated with metabolic traits including insulin sensitivity (SI) or fasting glucose in either population, but nonsynonymous SNP rs34702397 (R94Q) was nominally associated with SI (uncorrected p = 0.05) and glucose-mediated glucose disposal (SG; uncorrected p = 0.03) in African Americans. No SNP altered measures of insulin secretion or obesity, nor was BGLAP expression associated with rs1800247. Our study was sufficiently powered to exclude BGLAP variants as a major risk factor (OR > 1.5) for T2D in Caucasians, but coding variants in exon 4 may alter glucose homeostasis and diabetes risk in African Americans.
doi:10.3233/DMA-2010-0701
PMCID: PMC3304587  PMID: 20592451
Osteocalcin; diabetes; polymorphism; transcript; association; insulin sensitivity
23.  DYF-1 Is Required for Assembly of the Axoneme in Tetrahymena thermophila▿ †  
Eukaryotic Cell  2009;8(9):1397-1406.
In most cilia, the axoneme can be subdivided into three segments: proximal (the transition zone), middle (with outer doublet microtubules), and distal (with singlet extensions of outer doublet microtubules). How the functionally distinct segments of the axoneme are assembled and maintained is not well understood. DYF-1 is a highly conserved ciliary protein containing tetratricopeptide repeats. In Caenorhabditis elegans, DYF-1 is specifically needed for assembly of the distal segment (G. Ou, O. E. Blacque, J. J. Snow, M. R. Leroux, and J. M. Scholey. Nature. 436:583-587, 2005). We show that Tetrahymena cells lacking an ortholog of DYF-1, Dyf1p, can assemble only extremely short axoneme remnants that have structural defects of diverse natures, including the absence of central pair and outer doublet microtubules and incomplete or absent B tubules on the outer microtubules. Thus, in Tetrahymena, DYF-1 is needed for either assembly or stability of the entire axoneme. Our observations support the conserved function for DYF-1 in axoneme assembly or stability but also show that the consequences of loss of DYF-1 for axoneme segments are organism specific.
doi:10.1128/EC.00378-08
PMCID: PMC2747827  PMID: 19581442
24.  Automated medical image segmentation techniques 
Accurate segmentation of medical images is a key step in contouring during radiotherapy planning. Computed topography (CT) and Magnetic resonance (MR) imaging are the most widely used radiographic techniques in diagnosis, clinical studies and treatment planning. This review provides details of automated segmentation methods, specifically discussed in the context of CT and MR images. The motive is to discuss the problems encountered in segmentation of CT and MR images, and the relative merits and limitations of methods currently available for segmentation of medical images.
doi:10.4103/0971-6203.58777
PMCID: PMC2825001  PMID: 20177565
Artificial intelligence techniques; computed tomography; magnetic resonance imaging; medical images artifacts; segmentation
25.  Identification and modeling of a drug target for Clostridium perfringens SM101 
Bioinformation  2010;4(7):278-289.
In the present study, comparative genome analysis between Clostridium perfringens and the human genome was carried out to identify genes that are essential for the pathogen's survival, and non-homologous to the genes of human host, that can be used as potential drug targets. The study resulted in the identification of 426 such genes. The number of these potential drug targets thus identified is significantly lower than the genome's protein coding capacity (2558 protein coding genes). The 426 genes of C. perfringens were further analyzed for overall similarities with the essential genes of 14 different bacterial species present in Database of Essential Genes (DEG). Our results show that there are only 5 essential genes of C. perfringens that exhibit similarity with 12 species of the 14 different bacterial species present in DEG database. Of these, 1 gene was similar in 12 species and 4 genes were similar in 11 species. Thus, the study opens a new avenue for the development of potential drugs against the highly pathogenic bacterium. Further, by selecting these essential genes of C. perfringens, which are common and essential for other pathogenic microbial species, a broad spectrum anti-microbial drug can be developed. As a case study, we have built a homology model of one of the potential drug targets, ABC transporter-ATP binding protein, which can be employed for in silico docking studies by suitable inhibitors.
PMCID: PMC2957761  PMID: 20978600
Clostridium perfringens; DEG; Essential genes; Drug targets; Broad-spectrum anti microbial drug

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