Shailaja Sopory

Translational Health Science and Technology Institute

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Nitya Wadhwa

Translational Health Science and Technology Institute

Shinjini Bhatnagar

Translational Health Science and Technology Institute

Uma Chandra Mouli Natchu

Society for Applied Studies

Ramachandran Thiruvengadam

Translational Health Science and Technology Institute

Vineeta Bal

National Institute of Immunology

Satyajit Rath

Institute of Oceanology

Bapu Koundinya Desiraju

Translational Health Science and Technology Institute

Pallavi Kshetrapal

Translational Health Science and Technology Institute

Harish Chellani

Vardhman Mahavir Medical College & Safdarjung Hospital

Sumit Misra

Translational Health Science and Technology Institute

Cooperative Institutions

Translational Health Science and Technology Institute

All India Institute of Medical Sciences

All India Institute of Medical Sciences Raipur

All India Institute of Medical Sciences Bhopal

Public Health Laboratory Ivo de Carneri

Cincinnati Children's Hospital Medical Center

World Health Organization

Johns Hopkins University

Aga Khan University

National Institute of Immunology

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Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multi-country meta-analysis

medRxiv (Cold Spring Harbor Laboratory) (2022)

Nagendra Monangi Huan Xu Yue‐Mei Fan Rasheda Khanam Waqasuddin Khan

ABSTRACT Background Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). We aimed to determine the association of maternal plasma/serum Cu concentrations during pregnancy with PTB risk and gestational duration in a large multi-cohort study including diverse populations. Methods Gestational duration data and maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal plasma or serum Cu concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) analysis. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute phase reactants (APRs), malaria, and HIV infection were analyzed in 1239 samples from the Malawi cohort. Findings The maternal prenatal Cu concentration in our study samples followed a normal distribution with a mean of 1.92 μg/ml and a standard deviation of 0.43 μg/ml, and Cu concentrations increased with gestational age up to 20 weeks. The random effect meta-analysis across the 18 cohorts revealed that 1 μg/ml increase in maternal Cu concentration before the third trimester was associated with a higher risk of PTB with an OR of 1.30 (95% CI: 1.08 to 1.57) and shorter gestational duration of 1.64 days (95% CI: 0.56 to 2.73). The estimated effects were generally consistent across all sites. In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. Interpretation Our study supports a robust negative association between maternal mid-gestation Cu concentration and gestational duration and a positive association with risk for preterm birth. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as a potential marker of the integrated inflammatory pathways during pregnancy and risk for preterm birth.

10.1101/2022.08.27.22278198

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The prodomain of BMP4 is necessary and sufficient to generate stable BMP4/7 heterodimers with enhanced bioactivity in vivo

Proceedings of the National Academy of Sciences (2015)

Judith M. Neugebauer Sunjong Kwon Hyung-Seok Kim Nathan Donley Anup Tilak

Significance Bone morphogenetic proteins (BMPs) are made as inactive precursor proteins that dimerize and are cleaved to generate a bioactive ligand along with prodomain fragments that lack signaling activity. BMP ligands signal as either homodimers, or as heterodimers that display significantly higher activity in vivo. Recombinant homodimeric BMP ligands are used clinically to stimulate bone healing, but this requires supraphysiological doses due to the short half-life of the implanted protein. The current studies demonstrate that properties intrinsic to the BMP4 prodomain contribute to the formation and activity of BMP homodimers and heterodimers in vivo. Understanding how the prodomain regulates the activity of the ligand when it is made in vivo may lead to changes in the way BMP ligands are used clinically.

HEK 293 cells

10.1073/pnas.1501449112

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Citations (42)

Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children

Kidney International (2014)

Aditi Sinha Jaya Bajpai Savita Saini Divya Bhatia Aarti Gupta

SuPAR

Minimal change disease

Nephrosis

10.1038/ki.2013.546

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Development and external validation of Indian population-specific Garbhini-GA2 model for estimating gestational age in second and third trimesters

The Lancet Regional Health - Southeast Asia (2024)

Veerendra P. Gadekar Nikhita Damaraju Ashley Xavier Shambo Basu Thakur Ramya Vijayram

A large proportion of pregnant women in lower and middle-income countries (LMIC) seek their first antenatal care after 14 weeks of gestation. While the last menstrual period (LMP) is still the most prevalent method of determining gestational age (GA), ultrasound-based foetal biometry is considered more accurate in the second and third trimesters. In LMIC settings, the Hadlock formula, originally developed using data from a small Caucasian population, is widely used for estimating GA and foetal weight worldwide as the pre-programmed formula in ultrasound machines. This approach can lead to inaccuracies when estimating GA in a diverse population. Therefore, this study aimed to develop a population-specific model for estimating GA in the late trimesters that was as accurate as the GA estimation in the first trimester, using data from GARBH-Ini, a pregnancy cohort in a North Indian district hospital, and subsequently validate the model in an independent cohort in South India.

Third trimester

10.1016/j.lansea.2024.100362

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Flow cytometric-gating strategies for major cell lineages from cord blood.

K. Rathore Deepak Nair Deepa Saimah Raza Savita Saini Singh Reeta

10.1371/journal.pone.0123589.g001

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TLR-mediated albuminuria needs TNFα-mediated co-operativity between TLRs present in hematopoietic tissues and CD80 present on non-hematopoietic tissues

Disease Models & Mechanisms (2016)

Nidhi Jain Bhavya Khullar Neelam Oswal Balaji Banoth Prashant Joshi

Transient albuminuria induced by pathogen-associated molecular patterns (PAMPs) in mice through engagement of Toll-like receptors (TLRs) is widely studied as a partial model for some forms of human nephrotic syndrome (NS). In addition to TLRs, CD80 has been shown to be essential for PAMP-mediated albuminuria. However, the mechanistic relationships between TLRs, CD80 and albuminuria remain unclear. Here, we show that albuminuria and CD80-uria induced in mice by many TLR ligands are dependent on the expression of TLRs and their downstream signalling intermediate MyD88 exclusively in hematopoietic cells and, conversely, on CD80 expression exclusively in non-hematopoietic cells. TNFα is crucial for TLR-mediated albuminuria and CD80-uria, and induces CD80 expression in cultured renal podocytes. IL-10 from hematopoietic cells ameliorates TNFα production, albuminuria and CD80-uria but does not prevent TNFα-mediated induction of podocyte CD80 expression. Chitohexaose, a small molecule originally of parasite origin, mediates TLR4-dependent anti-inflammatory responses, and blocks TLR-mediated albuminuria and CD80-uria through IL-10. Thus, TNFα is a prominent mediator of renal CD80 induction and resultant albuminuria in this model, and small molecules modulating TLR-mediated inflammatory activation might have contributory or adjunct therapeutic potential in some contexts of NS development.

Albuminuria

CD80

Proinflammatory cytokine

10.1242/dmm.023440

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VP35.14: Ultrasound‐based assessment of fetal growth in a North Indian population compared with known growth standards: a hospital‐based longitudinal study

Ultrasound in Obstetrics and Gynecology (2021)

K Kaushal Anusha Sachan Aman Khurana Nitya Wadhwa Sumit Misra

Assessing fetal growth during pregnancy is important for monitoring the well-being of the fetus. In this study we describe longitudinal fetal growth patterns in a North Indian population and estimate the prevalence of small for gestational age using growth charts available globally. Data on 2780 pregnancies with accurate dating information and singleton live births were collected in a hospital-based GARBH-Ini pregnancy cohort, Haryana, India from May 2015 to June 2020. We obtained fetal biometry at 18–20, 30–32 and 35–37 weeks. Fetal weight (EFW) was estimated using Hadlock-3 formula. Fetal growth trajectories were constructed using GAMLSS model. We used the Fetal Growth Percentile software (FetalGPSR package) to calculate the EFW percentile against five standards (WHO, Intergrowth 21st (IG21st), NICHD, FMF and Hadlock) and calculated the proportion of small for gestational age (SGA). At birth, anthropometry was evaluated using IG21st and Fenton's standards. Delphi consensus definitions were used to estimate the proportions of fetal growth restriction (FGR). Proportions of SGA varied widely (between 12.5–52.3% at 30–32 weeks and 21–57.4% at 35–37 weeks) with the lowest when compared against IG21st and highest with FMF charts. As the gestation progresses, from 30–32 weeks to 35–37 weeks there is a 1.4–2 fold increase of SGA. IG21st classified lesser number of babies as SGA at birth as compared to Fenton charts. In order to resolve these differences, we used the Delphi consensus definitions and estimated that 11.6%, 15.9% and 28.6 % were early, late FGR and FGR at birth respectively. We report a longitudinal description of fetal growth in a North Indian population using references and standards available globally. The proportions of SGA varied widely with the choice of reference/standard. Fetal growth restriction progressively aggravates with gestation. The Delphi consensus definition may be a solution to provide estimates of FGR that can be interchangeably used globally.

Fetal growth

Intrauterine growth restriction

10.1002/uog.24535

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The cGMP-binding, cGMP-specific phosphodiesterase (PDE5): intestinal cell expression, regulation and role in fluid secretion

Cellular Signalling (2003)

Shailaja Sopory Tanvir Kaur Sandhya S. Visweswariah

Phosphodiesterase 3

PDE10A

Jejunum

10.1016/j.cellsig.2003.11.004

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Citations (28)

Classical monocytes, myeloid and plasmacytoid DCs as well as mDC: pDC ratios differ between AGA and SGA cord blood.

K. Rathore Deepak Nair Deepa Saimah Raza Savita Saini Singh Reeta

Cord blood

Monocyte

10.1371/journal.pone.0123589.g004

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The GAF Domain of the cGMP-Binding, cGMP-Specific Phosphodiesterase (PDE5) Is a Sensor and a Sink for cGMP

Biochemistry (2008)

Kabir H. Biswas Shailaja Sopory Sandhya S. Visweswariah

We describe here a novel sensor for cGMP based on the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase 5 (PDE5) using bioluminescence resonance energy transfer (BRET). The wild type GAFa domain, capable of binding cGMP with high affinity, and a mutant (GAFaF163A) unable to bind cGMP were cloned as fusions between GFP and Rluc for BRET2 assays. BRET2 ratios of the wild type GAFa fusion protein, but not GAFaF163A, increased in the presence of cGMP but not cAMP. Higher basal BRET2 ratios were observed in cells expressing the wild type GAFa domain than in cells expressing GAFaF163A. This was correlated with elevated basal intracellular levels of cGMP, indicating that the GAF domain could act as a sink for cGMP. The tandem GAF domains in full length PDE5 could also sequester cGMP when the catalytic activity of PDE5 was inhibited. Therefore, these results describe a cGMP sensor utilizing BRET2 technology and experimentally demonstrate the reservoir of cGMP that can be present in cells that express cGMP-binding GAF domain-containing proteins. PDE5 is the target for the anti-impotence drug sildenafil citrate; therefore, this GAF-BRET2 sensor could be used for the identification of novel compounds that inhibit cGMP binding to the GAF domain, thereby regulating PDE5 catalytic activity.

PDE10A

cGMP-dependent protein kinase

Phosphodiesterase 3

10.1021/bi702025w

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Citations (59)