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1.  Genetic variants in microRNAs and breast cancer risk in African American and European American women 
Breast cancer research and treatment  2013;141(3):10.1007/s10549-013-2698-4.
MicroRNAs (miRNAs) are an integral part of the post-transcriptional machinery of gene expression and have been implicated in the carcinogenic cascade. Single nucleotide polymorphisms (SNPs) in miRNAs and risk of breast cancer have been evaluated in populations of European or Asian ancestry, but not among women of African ancestry. Here we examined 145 SNPs in 6 miRNA processing genes and in 78 miRNAs which target genes known to be important in breast cancer among 906 African American (AA) and 653 European American (EA) cases and controls enrolled in the Women’s Circle of Health Study (WCHS). Allele frequencies of most SNPs (87%) differed significantly by race. We found a number of SNPs in miRNAs and processing genes in association with breast cancer overall or stratified by estrogen receptor (ER) status. Several associations were significantly different by race, with none of the associations being significant in both races. Using a polygenic risk score to combine the effects of multiple SNPs, we found significant associations with the score in each subgroup analysis. For ER-positive cancer, each unit increment of the risk score was associated with a 51% increased risk in AAs (OR=1.51, 95% CI=1.30–1.74, p=3.3*10−8) and a 73% increased risk in EAs (OR=1.73, 95% CI=1.45–2.06, p=1.4*10−9). These data show, for the first time, that miRNA-related genetic variations may underlie the etiology of breast cancer in both populations of African and European ancestries. Future studies are needed to validate our findings and to explore the underlying mechanisms.
doi:10.1007/s10549-013-2698-4
PMCID: PMC3856568  PMID: 24062209
microRNA; SNP; breast cancer; epidemiology; estrogen receptor; polygenic risk score
2.  Multiple Shocks, Coping and Welfare Consequences: Natural Disasters and Health Shocks in the Indian Sundarbans 
PLoS ONE  2014;9(8):e105427.
Background
Based on a household survey in Indian Sundarbans hit by tropical cyclone Aila in May 2009, this study tests for evidence and argues that health and climatic shocks are essentially linked forming a continuum and with exposure to a marginal one, coping mechanisms and welfare outcomes triggered in the response is significantly affected.
Data & Methods
The data for this study is based on a cross-sectional household survey carried out during June 2010. The survey was aimed to assess the impact of cyclone Aila on households and consequent coping mechanisms in three of the worst-affected blocks (a sub-district administrative unit), viz. Hingalganj, Gosaba and Patharpratima. The survey covered 809 individuals from 179 households, cross cutting age and gender. A separate module on health-seeking behaviour serves as the information source of health shocks defined as illness episodes (ambulatory or hospitalized) experienced by household members.
Key findings
Finding reveals that over half of the households (54%) consider that Aila has dealt a high, damaging impact on their household assets. Result further shows deterioration of health status in the period following the incidence of Aila. Finding suggests having suffered multiple shocks increases the number of adverse welfare outcomes by 55%. Whereas, suffering either from the climatic shock (33%) or the health shock (25%) alone increases such risks by a much lesser extent. The multiple-shock households face a significantly higher degree of difficulty to finance expenses arising out of health shocks, as opposed to their counterparts facing only the health shock. Further, these households are more likely to finance the expenses through informal loans and credit from acquaintances or moneylenders.
Conclusion
This paper presented empirical evidence on how natural and health shocks mutually reinforce their resultant impact, making coping increasingly difficult and present significant risks of welfare loss, having short as well as long-run development manifestations.
doi:10.1371/journal.pone.0105427
PMCID: PMC4149427  PMID: 25170846
3.  Cofactor Independent Phosphoglycerate Mutase of Brugia malayi Induces a Mixed Th1/Th2 Type Immune Response and Inhibits Larval Development in the Host 
BioMed Research International  2014;2014:590281.
Lymphatic filariasis is a major debilitating disease, endemic in 72 countries putting more than 1.39 billion people at risk and 120 million are already infected. Despite the significant progress in chemotherapeutic advancements, there is still need for other measures like development of an effective vaccine or discovery of novel drug targets. In this study, structural and immunological characterization of independent phosphoglycerate mutase of filarial parasite Brugia malayi was carried out. Protein was found to be expressed in all major parasite life stages and as an excretory secretory product of adult parasites. Bm-iPGM also reacted to all the categories of human bancroftian patient's sera including endemic normals. In vivo immunological behaviour of protein was determined in immunized BALB/c mice followed by prophylactic analysis in BALB/c mice and Mastomys coucha. Immunization with Bm-iPGM led to generation of a mixed Th1/Th2 type immune response offering 58.2% protection against larval challenge in BALB/c and 65–68% protection in M. coucha. In vitro studies confirmed participation of anti-Bm-iPGM antibodies in killing of B. malayi infective larvae and microfilariae through ADCC mechanism. The present findings reveal potential immunoprotective nature of Bm-iPGM advocating its worth as an antifilarial vaccine candidate.
doi:10.1155/2014/590281
PMCID: PMC4100390  PMID: 25061608
4.  Two functional serotonin polymorphisms moderate the effect of food reinforcement on BMI 
Behavioral neuroscience  2013;127(3):387-399.
Food reinforcement, or the motivation to eat, has been associated with increased energy intake, greater body weight and prospective weight gain. Much of the previous research on the reinforcing value of food has focused on the role of dopamine, but it may be worthwhile to examine genetic polymorphisms in the serotonin and opioid systems as these neurotransmitters have been shown to be related to reinforcement processes and to influence energy intake. We examined the relationship among 44 candidate genetic polymorphisms in the dopamine, serotonin and opioid systems, and food reinforcement and body mass index (BMI) in a sample of 245 individuals. Polymorphisms in the Monoamine oxidase A (MAOA-LPR) and serotonin receptor 2A genes (rs6314) moderated the effect of food reinforcement on BMI, accounting for an additional 5-10% variance and revealed a potential role of the single nucleotide polymorphism, rs6314 in the serotonin 2A receptor as a differential susceptibility factor for obesity. Differential susceptibility describes a factor that can confer either risk or protection depending on a second variable, such that rs6314 is predictive of both high and low BMI based on the level of food reinforcement, while the diathesis stress or dual-gain model influences only one end of the outcome measure. The interaction with MAOA-LPR better fit the dual-risk or diathesis stress model, with the 3.5R/4R allele conferring protection for individuals low in food reinforcement. These results provide new insight into genes theoretically involved in obesity and support the hypothesis that genetics moderate the association between food reinforcement on BMI.
doi:10.1037/a0032026
PMCID: PMC4049455  PMID: 23544600
Obesity; dopamine; serotonin; food reinforcement; differential susceptibility
5.  Recruitment of NCOR1 to VDR target genes is enhanced in prostate cancer cells and associates with altered DNA methylation patterns 
Carcinogenesis  2012;34(2):248-256.
The current study investigated transcriptional distortion in prostate cancer cells using the vitamin D receptor (VDR) as a tool to examine how epigenetic events driven by corepressor binding and CpG methylation lead to aberrant gene expression. These relationships were investigated in the non-malignant RWPE-1 cells that were 1α,25(OH)2D3 responsive (RWPE-1) and malignant cell lines that were 1α,25(OH)2D3 partially responsive (RWPE-2) and resistant (PC-3). These studies revealed that selective attenuation and repression of VDR transcriptional responses in the cancer cell lines reflected their loss of antiproliferative sensitivity. This was evident in VDR target genes including VDR, CDKN1A (encodes p21(waf1/cip1)) and GADD45A; NCOR1 knockdown alleviated this malignant transrepression. ChIP assays in RWPE-1 and PC-3 cells revealed that transrepression of CDKN1A was associated with increased NCOR1 enrichment in response to 1α,25(OH)2D3 treatment. These findings supported the concept that retained and increased NCOR1 binding, associated with loss of H3K9ac and increased H3K9me2, may act as a beacon for the initiation and recruitment of DNA methylation. Overexpressed histone methyltransferases (KMTs) were detectable in a wide panel of prostate cancer cell lines compared with RWPE-1 and suggested that generation of H3K9me2 states would be favored. Cotreatment of cells with the KMT inhibitor, chaetocin, increased 1α,25(OH)2D3-mediated induction of CDKN1A expression supporting a role for this event to disrupt CDKN1A regulation. Parallel surveys in PC-3 cells of CpG methylation around the VDR binding regions on CDKN1A revealed altered basal and VDR-regulated DNA methylation patterns that overlapped with VDR-induced recruitment of NCOR1 and gene transrepression. Taken together, these findings suggest that sustained corepressor interactions with nuclear-resident transcription factors may inappropriately transform transient-repressive histone states into more stable and repressive DNA methylation events.
doi:10.1093/carcin/bgs331
PMCID: PMC3564435  PMID: 23087083
6.  Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients 
Oncotarget  2014;5(3):824-840.
We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p <.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.
PMCID: PMC3996656  PMID: 24583788
Prostate cancer; microRNA; biochemical progression; miR-103; miR-125b; miR-222; cancer epigenetics
7.  Evaluation of Phytase Producing Bacteria for Their Plant Growth Promoting Activities 
Bacterial inoculants are known to possess plant growth promoting abilities and have potential as liquid biofertilizer application. Four phytase producing bacterial isolates (phytase activity in the range of 0.076–0.174 U/mL), identified as Advenella species (PB-05, PB-06, and PB-10) and Cellulosimicrobium sp. PB-09, were analyzed for their plant growth promoting activities like siderophore production, IAA production, HCN production, ammonia production, phosphate solubilization, and antifungal activity. All isolates were positive for the above characteristics except for HCN production. The solubilization index for phosphorus on Pikovskaya agar plates was in the range of 2–4. Significant amount of IAA (7.19 to 35.03 μg/mL) production and solubilized phosphate (189.53 to 746.84 μg/mL) was noticed by these isolates at different time intervals. Besides that, a greenhouse study was also conducted with Indian mustard to evaluate the potential of these isolates to promote plant growth. Effect of seed bacterization on various plant growth parameters and P uptake by plant were used as indicators. The plant growth promoting ability of bacterial isolates in pot experiments was correlated to IAA production, phosphate solubilization, and other in vitro tests. On the basis of present findings, isolate PB-06 was most promising in plant growth promotion with multiple growth promoting characteristics.
doi:10.1155/2014/426483
PMCID: PMC3941791  PMID: 24669222
8.  Equity in maternal, newborn, and child health care coverage in India 
Global Health Action  2013;6:10.3402/gha.v6i0.22217.
Background
Addressing inequitable coverage of maternal and child health care services among different socioeconomic strata of population and across states is an important part of India's contemporary health program. This has wide implications for the achievement of the Millennium Development Goal targets.
Objective
This paper assesses the inequity in coverage of maternal, newborn, and child health (MNCH) care services across household wealth quintiles in India and its states.
Design
Utilizing the District Level Household and Facility Survey conducted during 2007–08, this paper has constructed a Composite Coverage Index (CCI) in MNCH care.
Results
The mean overall coverage of 45% was estimated at the national level, ranging from 31% for the poorest to 60% for the wealthiest quintile. Moreover, a massive state-wise difference across wealth quintiles was observed in the mean overall CCI. Almost half of the Indian states and union territories recorded a ≤50% coverage in MNCH care services, which demands special attention.
Conclusion
India needs focused efforts to address the inequity in coverage of health care services by recognising or defining underserved people and pursuing well-planned time-oriented health programs committed to ameliorate the present state of MNCH care.
doi:10.3402/gha.v6i0.22217
PMCID: PMC3772319  PMID: 24119659
maternal; newborn and child health; composite coverage index; household economic status; states; India; millennium development goals
9.  Trends in Child Immunization across Geographical Regions in India: Focus on Urban-Rural and Gender Differentials 
PLoS ONE  2013;8(9):e73102.
Background
Although child immunization is regarded as a highly cost-effective lifesaver, about fifty percent of the eligible children aged 12–23 months in India are without essential immunization coverage. Despite several programmatic initiatives, urban-rural and gender difference in child immunization pose an intimidating challenge to India’s public health agenda. This study assesses the urban-rural and gender difference in child immunization coverage during 1992–2006 across six major geographical regions in India.
Data and Methods
Three rounds of the National Family Health Survey (NFHS) conducted during 1992–93, 1998–99 and 2005–06 were analyzed. Bivariate analyses, urban-rural and gender inequality ratios, and the multivariate-pooled logistic regression model were applied to examine the trends and patterns of inequalities over time.
Key Findings
The analysis of change over one and half decades (1992–2006) shows considerable variations in child immunization coverage across six geographical regions in India. Despite a decline in urban-rural and gender differences over time, children residing in rural areas and girls remained disadvantaged. Moreover, northeast, west and south regions, which had the lowest gender inequality in 1992 observed an increase in gender difference over time. Similarly, urban-rural inequality increased in the west region during 1992–2006.
Conclusion
This study suggests periodic evaluation of the health care system is vital to assess the between and within group difference beyond average improvement. It is essential to integrate strong immunization systems with broad health systems and coordinate with other primary health care delivery programs to augment immunization coverage.
doi:10.1371/journal.pone.0073102
PMCID: PMC3762848  PMID: 24023816
10.  Immunization of Mastomys coucha with Brugia malayi Recombinant Trehalose-6-Phosphate Phosphatase Results in Significant Protection against Homologous Challenge Infection 
PLoS ONE  2013;8(8):e72585.
Development of a vaccine to prevent or reduce parasite development in lymphatic filariasis would be a complementary approach to existing chemotherapeutic tools. Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine target due to its absence in mammals, prevalence in the major life stages of the parasite and immunoreactivity with human bancroftian antibodies, especially from endemic normal subjects. We have recently reported on the cloning, expression, purification and biochemical characterization of this vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of Bm-TPP was carried out against B. malayi larval challenge in a susceptible host Mastomys coucha and the protective ability of the recombinant protein was evaluated by observing the adverse effects on microfilarial density and adult worm establishment. Immunization caused 78.4% decrease in microfilaremia and 71.04% reduction in the adult worm establishment along with sterilization of 70.06% of the recovered live females. The recombinant protein elicited a mixed Th1/Th2 type of protective immune response as evidenced by the generation of both pro- and anti-inflammatory cytokines IL-2, IFN-γ, TNF-α, IL-4 and an increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus immunization with Bm-TPP conferred considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis (LF).
doi:10.1371/journal.pone.0072585
PMCID: PMC3755969  PMID: 24015262
11.  The Interactions of microRNA and Epigenetic Modifications in Prostate Cancer 
Cancers  2013;5(3):998-1019.
Epigenetic modifiers play important roles in fine-tuning the cellular transcriptome. Any imbalance in these processes may lead to abnormal transcriptional activity and thus result in disease state. Distortions of the epigenome have been reported in cancer initiation and progression. DNA methylation and histone modifications are principle components of this epigenome, but more recently it has become clear that microRNAs (miRNAs) are another major component of the epigenome. Interactions of these components are apparent in prostate cancer (CaP), which is the most common non-cutaneous cancer and second leading cause of death from cancer in the USA. Changes in DNA methylation, altered histone modifications and miRNA expression are functionally associated with CaP initiation and progression. Various aspects of the epigenome have also been investigated as biomarkers for different stages of CaP detection, though with limited success. This review aims to summarize key aspects of these mechanistic interactions within the epigenome and to highlight their translational potential as functional biomarkers. To this end, exploration of TCGA prostate cancer data revealed that expression of key CaP miRNAs inversely associate with DNA methylation. Given the importance and prevalence of these epigenetic events in CaP biology it is timely to understand further how different epigenetic components interact and influence each other.
doi:10.3390/cancers5030998
PMCID: PMC3795376  PMID: 24202331
epigenetics; DNA methylation; histone modifications; microRNA; prostate cancer; cancer
12.  Socioeconomic Disparities in Maternity Care among Indian Adolescents, 1990–2006 
PLoS ONE  2013;8(7):e69094.
Background
India, with a population of more than 1.21 billion, has the highest maternal mortality in the world (estimated to be 56000 in 2010); and adolescent (aged 15–19) mortality shares 9% of total maternal deaths. Addressing the maternity care needs of adolescents may have considerable ramifications for achieving the Millennium Development Goal (MDG)–5. This paper assesses the socioeconomic differentials in accessing full antenatal care and professional attendance at delivery by adolescent mothers (aged 15–19) in India during 1990–2006.
Methods and Findings
Data from three rounds of the National Family Health Survey of India conducted during 1992–93, 1998–99, and 2005–06 were analyzed. The Cochran-Armitage and Chi-squared test for linear and non-linear time trends were applied, respectively, to understand the trend in the proportion of adolescent mothers utilizing select maternity care services during 1990–2006. Using pooled multivariate logistic regression models, the probability of select maternal healthcare utilization among women by key socioeconomic characteristics was appraised. After adjusting for potential socio-demographic and economic characteristics, the likelihood of adolescents accessing full antenatal care increased by only 4% from 1990 to 2006. However, the probability of adolescent women availing themselves of professional attendance at delivery increased by 79% during the same period. The study also highlights the desolate disparities in maternity care services among adolescents across the most and the least favoured groups.
Conclusion
Maternal care interventions in India need focused programs for rural, uneducated, poor adolescent women so that they can avail themselves of measures to delay child bearing, and for better antenatal consultation and delivery care in case of pregnancy. This study strongly advocates the promotion of a comprehensive ‘adolescent scheme’ along the lines of ‘Continuum of Maternal, Newborn and Child health Care’ to address the unmet need of reproductive and maternal healthcare services among adolescent women in India.
doi:10.1371/journal.pone.0069094
PMCID: PMC3720871  PMID: 23894412
13.  The Arabidopsis LECTIN RECEPTOR KINASE-VI.2 is a functional protein kinase and is dispensable for basal resistance to Botrytis cinerea 
Plant Signaling & Behavior  2012;8(1):e22611.
Sensing of microbial pathogens by pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) elicits a defense program known as PAMP-triggered immunity (PTI). Recently, we have shown that the Arabidopsis thaliana L-TYPE LECTIN RECEPTOR KINASE-VI.2 (LecRK-VI.2) positively regulates bacterial PTI. In this report, we suggest by in silico analysis that the kinase domain of LecRK-VI.2 is functional. LecRK-VI.2 also demonstrated auto-phosphorylation activity in vitro in the presence of divalent metal cations indicating that LecRK-VI.2 has the ability to auto-phosphorylate. We further investigate the role of LecRK-VI.2 in Arabidopsis resistance to the necrotrophic fungal pathogen Botrytis cinerea. Disruption of LecRK-VI.2 did not affect Arabidopsis resistance to B. cinerea. Accordingly, wild-type upregulation levels of PTI-responsive WRKY53, FRK1, NHL10, CYP81F2 and CBP60 g after treatment with the fungal PAMP chitin were observed in lecrk-VI.2-1. These data provide evidences that the kinase domain of LecRK-VI.2 is active and show that LecRK-VI.2 is not critical for resistance to the fungal pathogen B. cinerea.
doi:10.4161/psb.22611
PMCID: PMC3745566  PMID: 23221759
Arabidopsis thaliana; lectin receptor kinase; innate immunity; protein kinase; botrytis cinerea; chitin
14.  Chronic meningitis with multiple cranial neuropathies: A rare initial presentation of Wegener's granulomatosis 
Wegener's granulomatosis (WG) is a systemic necrotizing vasculitis that affects the small blood vessels. It mainly affects the upper and lower respiratory tract and kidneys. Central nervous system (CNS) involvement is rare, and has been reported only in about 8% of cases during the course of illness. Initial presentation with neurologic affection, particularly chronic hypertrophic meningitis is very unusual. We report the case of a 34 year old male who presented with chronic hypertrophic meningitis and multiple cranial nerve involvement as the initial manifestation, without respiratory and renal symptoms. This case highlights the difficulties in diagnosing a rare disease with rarer presentation, and at the same time illustrates that Wegener's granulomatosis should be considered in the differential diagnosis of chronic meningitis.
doi:10.4103/0972-2327.116920
PMCID: PMC3788296  PMID: 24101832
Chronic meningitis; cranial neuropathies; Wegener's granulomatosis
15.  In vitro gene silencing of independent phosphoglycerate mutase (iPGM) in the filarial parasite Brugia malayi 
Background
The phosphoglycerate mutase (PGM) enzyme catalyzes the interconversion of 2- and 3-phosphoglycerate in the glycolytic /gluconeogenic pathways that are present in the majority of cellular organisms. They can be classified as cofactor-dependent PGM (dPGM) or cofactor-independent PGM (iPGM). Vertebrates, yeasts, and many bacteria have only dPGM, while higher plants, nematodes, archaea, and many other bacteria have only iPGM. A small number of bacteria, including Escherichia coli and certain archaea and protozoa, contain both forms. The silencing of ipgm in Caenorhabditis elegans (C. elegans) has demonstrated the importance of this enzyme in parasite viability and, therefore, its potential as an anthelmintic drug target. In this study, the role of the Brugia malayi (B. malayi) ipgm in parasite viability, microfilaria release, embryogenesis, and in vivo development of infective larvae post-gene silencing was explored by applying ribonucleic acid (RNA) interference studies.
Results
The in vitro ipgm gene silencing by small interfering RNA (siRNA) leads to severe phenotypic deformities in the intrauterine developmental stages of female worms with a drastic reduction (~90%) in the motility of adult parasites and a significantly reduced (80%) release of microfilariae (mf) by female worms in vitro. Almost half of the in vitro-treated infective L3 displayed sluggish movement. The in vivo survival and development of siRNA-treated infective larvae (L3) was investigated in the peritoneal cavity of jirds where a ~45% reduction in adult worm establishment was observed.
Conclusion
The findings clearly suggest that iPGM is essential for both larval and adult stages of B. malayi parasite and that it plays a pivotal role in female worm embryogenesis. The results thus validate the Bm-iPGM as a putative anti-filarial drug target.
doi:10.1186/2049-9957-2-5
PMCID: PMC3707094  PMID: 23849829
siRNA; Lymphatic filariasis; Drug target; RNAi; Embryogenesis
16.  Serum Vitamin D Metabolites in Colorectal Cancer Patients Receiving Cholecalciferol Supplementation: Correlation with Polymorphisms in the Vitamin D Genes 
Hormones & Cancer  2013;4(4):242-250.
Cholecalciferol (D3) supplementation results in variable increases in serum 25(OH)D3 levels, however, the influence of genetic polymorphisms on these variable responses is unclear. We measured serum 25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3 and VDBP levels in 50 colorectal cancer (CRC) patients before and during 2,000 IU daily oral D3 supplementation for six months and in 263 archived CRC serum samples. Serum PTH levels and PBMC 24-OHase activity were also measured during D3 supplementation. TagSNPs in CYP2R1, CYP27A1, CYP27B1, CYP24A1, VDR, and GC genes were genotyped in all patients, and the association between these SNPs and serum vitamin D3 metabolites levels before and after D3 supplementation was analyzed. The mean baseline serum 25(OH)D3 level was less than 32 ng/mL in 65 % of the 313 CRC patients. In the 50 patients receiving D3 supplementation, serum levels of 25(OH)D3 increased (p = 0.008), PTH decreased (p = 0.036) and 24,25(OH)2D3, 1,25(OH)2D3, VDBP levels and PBMC 24-OHase activity were unchanged. GC SNP rs222016 was associated with high 25(OH)D3 and 1,25(OH)2D3 levels at baseline while rs4588 and rs2282679 were associated with lower 25(OH)D3 and 1,25(OH)2D3 levels both before and after D3 supplementation. CYP2R1 rs12794714 and rs10500804 SNPs were significantly associated with low 25(OH)D3 levels after supplementation but not with baseline 25(OH)D3. Our results show that D3 supplementation increased 25(OH)D3 levels in all patients. GC rs4588 and rs2283679 SNPs were associated with increased risk of vitamin D3 insufficiency and suboptimal increase in 25(OH)D3 levels after D3 supplementation. Individuals with these genotypes may require higher D3 supplementation doses to achieve vitamin D3 sufficiency.
doi:10.1007/s12672-013-0139-9
PMCID: PMC3689467  PMID: 23456391
17.  Lectin receptor kinases in plant innate immunity 
A key feature of innate immunity is the ability to recognize and respond to potential pathogens in a highly sensitive and specific manner. In plants, the first layer of defense is induced after recognition by pattern recognition receptors of microbe-associated molecular patterns. This recognition elicits a defense program known as pattern-triggered immunity. Pathogen entry into host tissue is a critical early step in causing infection. For foliar bacterial pathogens, natural surface openings such as stomata, are important entry sites. Stomata in contact with bacteria rapidly close and can thus restrict bacterial entry into leaves. The molecular mechanisms regulating stomatal closure upon pathogen perception are not yet well-understood. Plant lectin receptor kinases are thought to play crucial roles during development and in the adaptive response to various stresses. Although the function of most plant lectin receptor kinases is still not clear, a role for this kinase family in plant innate immunity is emerging. Here, we summarize recent progresses in the identification of lectin receptor kinases involved in plant innate immunity. We also discuss the role of lectin receptor kinases in stomatal innate immunity signaling.
doi:10.3389/fpls.2013.00124
PMCID: PMC3646242  PMID: 23675375
plant; receptor-like kinase; lectin receptor kinase; innate immunity; stomatal innate immunity; bacteria
18.  Correlation of Pulse Oximetry and Apgar Scoring in the Normal Newborns 
Context:
Apgar score (AS) is routinely used for assessment of newborns immediately after birth. Within acceptable limits, low saturations at birth are normal in vigorous newborn babies. Various studies have questioned the reliability of AS.
Aims:
To detect whether AS is an accurate indicator of hypoxemia and to study the correlation of different components of AS with the arterial oxygenation saturation (SpO2) levels of normal newborns in the delivery room.
Settings and Design:
A prospective cross-sectional observational study on normal healthy neonates delivered vaginally in a tertiary level referral medical college.
Materials and Methods:
SpO2 levels were monitored continuously in the newborns with a pulse oximeter and serial recording of SpO2 levels was done at 5 min intervals starting at 1 min of life until 30 min after birth. Simultaneously, AS was recorded in these newborns at 1 and 5 min of life.
Statistical Analysis:
Data was analyzed using the Mann-Whitney–U test.
Results:
AS at 1 and 5 min of life didn’t correlate with the changes in SpO2 of newborns. In AS; though respiratory efforts and muscle tone were significantly correlated with SpO2 of the newborns, body color did not have significant correlation with simultaneously recorded SpO2.
Conclusions:
A revised AS in which evaluation of color is replaced by pulse oximetry monitoring would prove to be a better tool for neonatal evaluation in the immediate postnatal period.
doi:10.4103/2249-4847.109241
PMCID: PMC3761955  PMID: 24027740
Apgar score; neonatal monitoring; oxygen saturation level; pulse oximetry
19.  Synthesis, Spectroscopic Characterization, and In Vitro Antimicrobial Studies of Pyridine-2-Carboxylic Acid N′-(4-Chloro-Benzoyl)-Hydrazide and Its Co(II), Ni(II), and Cu(II) Complexes 
N-substituted pyridine hydrazide (pyridine-2-carbonyl chloride and 4-chloro-benzoic acid hydrazide) undergoes hydrazide formation of the iminic carbon nitrogen double bond through its reaction with cobalt(II), nickel(II), and copper(II) metal salts in ethanol which are reported and characterized based on elemental analyses, IR, solid reflectance, magnetic moment, molar conductance, and thermal analysis (TG). From the elemental analyses data, 1 : 2 metal complexes are formed having the general formulae [MCl2(HL)2] ·yH2O (where M = Co(II), Ni(II), and Cu(II), y = 1–3). The important infrared (IR) spectral bands corresponding to the active groups in the ligand and the solid complexes under investigation were studied. IR spectra show that ligand is coordinated to the metal ions in a neutral bidentate manner with ON donor sites. The solid complexes have been synthesized and studied by thermogravimetric analysis. All the metal chelates are found to be nonelectrolytes. From the magnetic and solid reflectance spectra, the complexes (cobalt(II), nickel(II), and copper(II)) have octahedral and square planner geometry, respectively. The antibacterial and antifungal activity's data show that the metal complexes have a promising biological activity comparable with the parent ligand against bacterial and fungal species.
doi:10.1155/2012/104549
PMCID: PMC3485482  PMID: 23125560
20.  Examining the Effect of Household Wealth and Migration Status on Safe Delivery Care in Urban India, 1992–2006 
PLoS ONE  2012;7(9):e44901.
Background
Although the urban health issue has been of long-standing interest to public health researchers, majority of the studies have looked upon the urban poor and migrants as distinct subgroups. Another concern is, whether being poor and at the same time migrant leads to a double disadvantage in the utilization of maternal health services? This study aims to examine the trends and factors that affect safe delivery care utilization among the migrants and the poor in urban India.
Methodology/Principal Findings
Using data from the National Family Health Survey, 1992–93 and 2005–06, this study grouped the household wealth and migration status into four distinct categories poor-migrant, poor-non migrant, non poor-migrant, non poor-non migrant. Both chi-square test and binary logistic regression were performed to examine the influence of household wealth and migration status on safe delivery care utilization among women who had experienced a birth in the four years preceding the survey. Results suggest a decline in safe delivery care among poor-migrant women during 1992–2006. The present study identifies two distinct groups in terms of safe delivery care utilization in urban India – one for poor-migrant and one for non poor-non migrants. While poor-migrant women were most vulnerable, non poor-non migrant women were the highest users of safe delivery care.
Conclusion
This study reiterates the inequality that underlies the utilization of maternal healthcare services not only by the urban poor but also by poor-migrant women, who deserve special attention. The ongoing programmatic efforts under the National Urban Health Mission should start focusing on the poorest of the poor groups such as poor-migrant women. Importantly, there should be continuous evaluation to examine the progress among target groups within urban areas.
doi:10.1371/journal.pone.0044901
PMCID: PMC3436793  PMID: 22970324
21.  In Vitro Silencing of Brugia malayi Trehalose-6-Phosphate Phosphatase Impairs Embryogenesis and In Vivo Development of Infective Larvae in Jirds 
Background
The trehalose metabolic enzymes have been considered as potential targets for drug or vaccine in several organisms such as Mycobacterium, plant nematodes, insects and fungi due to crucial role of sugar trehalose in embryogenesis, glucose uptake and protection from stress. Trehalose-6-phosphate phosphatase (TPP) is one of the enzymes of trehalose biosynthesis that has not been reported in mammals. Silencing of tpp gene in Caenorhabditis elegans revealed an indispensable functional role of TPP in nematodes.
Methodology and Principal Findings
In the present study, functional role of B. malayi tpp gene was investigated by siRNA mediated silencing which further validated this enzyme to be a putative antifilarial drug target. The silencing of tpp gene in adult female B. malayi brought about severe phenotypic deformities in the intrauterine stages such as distortion and embryonic development arrest. The motility of the parasites was significantly reduced and the microfilarial production as well as their in vitro release from the female worms was also drastically abridged. A majority of the microfilariae released in to the culture medium were found dead. B. malayi infective larvae which underwent tpp gene silencing showed 84.9% reduced adult worm establishment after inoculation into the peritoneal cavity of naïve jirds.
Conclusions/Significance
The present findings suggest that B. malayi TPP plays an important role in the female worm embryogenesis, infectivity of the larvae and parasite viability. TPP enzyme of B. malayi therefore has the potential to be exploited as an antifilarial drug target.
Author Summary
Lymphatic filariasis, one of the neglected tropical diseases, is the second leading cause of permanent and long term disability. Control of the disease relies on the mass administration of drugs which mainly act on the microfilariae without substantial effect on adult worms. Drugs need to be continued for several years to block the transmission of infection which may result in to development of resistant parasites. The sugar trehalose has been shown to play several important functions in the nematodes, and trehalose biosynthetic enzymes have been considered as potential targets for drug or vaccine candidate. In the present study we silenced trehalose-6-phosphate phosphatase and studied the biological function of TPP enzyme in the filarial nematode B. malayi viability, female worm embryogenesis and establishment of infection in the host. In vitro gene silencing was done in adult parasites using 5 mM concentration of siRNA while 2 mM of siRNA was used to treat L3 which were further inoculated into the peritoneal cavity of jirds to study the effect of siRNA treatment on in vivo larval development. The present findings validate trehalose-6-phosphate phosphatase as a vital antifilarial drug target.
doi:10.1371/journal.pntd.0001770
PMCID: PMC3419221  PMID: 22905273
22.  The role of fluorodeoxyglucose positron emission tomography-computerized tomography in resolving therapeutic dilemmas in pediatric Hodgkin lymphoma 
Introduction:
Hodgkin lymphoma (HL) is a highly curable lymphoma with cure rates of over 80% and even higher with limited stage disease. Computerized tomography (CT) scan is currently the recommended modality in staging and assessment of response to therapy in patients with HL. However, CT has its limitations. This study describes our experience with patients of HL where fluorodeoxyglucose positron emission tomography (FDG-PET)-CT scan helped decide further management, after completion of chemotherapy.
Methodology:
This is a retrospective review of the records of children diagnosed with HL at our center. Patients with post-treatment CT scan showing evidence of residual disease, who underwent FDG-PET-CT for deciding further management, were included in the study.
Results:
Thirty one patients were diagnosed with HL during this period. Nine patients were eligible and underwent PET-CT. In 8 out of 9 patients, PET-CT showed no scan evidence of active disease. In one patient, FDG-PET-CT carried out after completion of chemotherapy showed evidence of active disease and was given radiotherapy.
Conclusion:
FDG-PET-CT is a promising modality in deciding further management when there is discordance between the post-treatment CT scan and clinical condition of the patient with HL thus avoiding unnecessary chemotherapy/radiotherapy.
doi:10.4103/0972-3919.112717
PMCID: PMC3728733  PMID: 23919065
Children; hodgkin lymphoma; positron emission tomography-computerized tomography
23.  Under-Five Mortality in High Focus States in India: A District Level Geospatial Analysis 
PLoS ONE  2012;7(5):e37515.
Background
This paper examines if, when controlling for biophysical and geographical variables (including rainfall, productivity of agricultural lands, topography/temperature, and market access through road networks), socioeconomic and health care indicators help to explain variations in the under-five mortality rate across districts from nine high focus states in India. The literature on this subject is inconclusive because the survey data, upon which most studies of child mortality rely, rarely include variables that measure these factors. This paper introduces these variables into an analysis of 284 districts from nine high focus states in India.
Methodology/Principal Findings
Information on the mortality indicator was accessed from the recently conducted Annual Health Survey of 2011 and other socioeconomic and geographic variables from Census 2011, District Level Household and Facility Survey (2007–08), Department of Economics and Statistics Divisions of the concerned states. Displaying high spatial dependence (spatial autocorrelation) in the mortality indicator (outcome variable) and its possible predictors used in the analysis, the paper uses the Spatial-Error Model in an effort to negate or reduce the spatial dependence in model parameters. The results evince that the coverage gap index (a mixed indicator of district wise coverage of reproductive and child health services), female literacy, urbanization, economic status, the number of newborn care provided in Primary Health Centers in the district transpired as significant correlates of under-five mortality in the nine high focus states in India. The study identifies three clusters with high under-five mortality rate including 30 districts, and advocates urgent attention.
Conclusion
Even after controlling the possible biophysical and geographical variables, the study reveals that the health program initiatives have a major role to play in reducing under-five mortality rate in the high focus states in India.
doi:10.1371/journal.pone.0037515
PMCID: PMC3356406  PMID: 22629412
24.  Genetic Ancestry, Self-Reported Race and Ethnicity in African Americans and European Americans in the PCaP Cohort 
PLoS ONE  2012;7(3):e30950.
Background
Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.
Methods
Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.
Results
Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered “no” to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.
Conclusions
Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.
doi:10.1371/journal.pone.0030950
PMCID: PMC3313995  PMID: 22479307
25.  Differential response to sustained stimulation by hCG & LH on goat ovarian granulosa cells 
Background & objectives:
Chapekar established a model of ovarian tumourigenesis in mice by splenic transplantation of ovaries, resulting in sustained luteinizing hormone (LH) levels because of absence of feedback inhibition. There is increasing evidence of the differential response to LH or hCG under various experimental conditions. The effect of sustained hormonal stimulation in long term cultures is sparsely investigated. The study is aimed to determine the role of hCG and LH stress on caprine ovarian granulosa cells and their downstream signaling in short and long term cultures.
Methods:
To study the response of hCG and LH stress and downstream signaling, short term cultures were set up by exposing goat ovarian granulosa cells in primary cultures to hCG and LH stress (levels beyond their physiological doses) for 5 days (P0). Cells were sub-cultured at sixth day and subjected to prolonged LH/ hCG stress for two weeks in passage 1(P1) (long term cultures). Downstream cell signaling molecules were assessed. Intracellular cAMP was estimated by ELISA. For PKA and PKC, activity assays were performed. pERK protein expressions in short term cultures were assessed by Western blot and flowcytometry; in long term cultures, pERK expression was analyzed by flowcytometry.
Results:
Differential effects on cell proliferation were observed in long term cultures, where the untreated and hCG exposed cells showed markedly reduced cell proliferation after second week of exposure while LH treated cells continued to proliferate. Different levels of cAMP, PKA, PKC and phosphorylated ERK1/2 were observed on short term and long term LH stimulation. On sustained hormonal stimulation, cAMP levels were significantly (P<0.05) higher in hCG treated cultures as compared to controls and LH treated cultures. LH led to maximal elevation of ERK in long term cultures.
Interpretation & Conclusions:
As pERK1/2 promotes cellular proliferation, activation of ERK1/2 in LH treated cultures may be responsible for sustained growth. Prolonged LH treatment promoted growth and proliferation in caprine ovarian granulosa cells whereas prolonged exposure to hCG led to elevated levels of cAMP and decreased the rate of proliferation. Defining the signals and second messengers that act as survival or apoptotic mediators may help in elucidation of the mechanisms controlling proliferation or programmed cell death in granulosa cells.
PMCID: PMC3361869  PMID: 22561619
Caprine; cell culture; cell proliferation; granulosa cells; hCG; LH

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