Publications by authors named "Priyanka Aggarwal"

27 Publications

  • Page 1 of 1

Hinge like domain motion facilitates human RBMS1 protein binding to proto-oncogene c-myc promoter.

Nucleic Acids Res 2021 06;49(10):5943-5955

Transcription Regulation group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi 110067, India.

DNA binding proteins recognize DNA specifically or non-specifically using direct and indirect readout mechanisms like sliding, hopping, and diffusion. However, a common difficulty in explicitly elucidating any particular mechanism of site-specific DNA-protein recognition is the lack of knowledge regarding target sequences and inadequate account of non-specific interactions, in general. Here, we decipher the structural basis of target search performed by the key regulator of expression of c-myc proto-oncogene, the human RBMS1 protein. In this study, we have shown the structural reorganization of this multi-domain protein required for recognizing the specific c-myc promoter sequence. The results suggest that a synergy between structural re-organization and thermodynamics is necessary for the recognition of target sequences. The study presents another perspective of looking at the DNA-protein interactions.
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http://dx.doi.org/10.1093/nar/gkab363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191779PMC
June 2021

Rotavirus Gastroenteritis in Eastern Uttar Pradesh, India.

Indian J Pediatr 2021 03 18;88(Suppl 1):66-71. Epub 2021 Jan 18.

The Wellcome Trust Research Laboratory, Christian Medical College, Vellore, Tamil Nadu, India.

Objective: To identify cases of rotavirus diarrhea in Uttar Pradesh among children less than 5 y of age presenting with acute gastroenteritis, to study the clinical profile of the cases and to identify the rotavirus genotypes.

Methods: Any child who is 0-59 mo of age who is admitted to the study facility with diarrhea as the presenting complaint were enrolled into the surveillance after obtaining informed consent. Clinical history and sociodemographic information was recorded for all the patients. Patients with dehydration were treated as per standard protocol. Stool samples were collected for isolation of rotavirus and identification of its genotype.

Results: Of the 418 stool specimens collected, rotavirus was isolated in 47 (11.33%) samples. Rotavirus gastroenteritis was most common below the age of two years. A significant difference in the clinical characteristics between children who were positive for rotavirus and those who tested negative were not observed in this study. But patients with rotavirus diarrhea had longer duration of hospital stay (OR 3.31; CI 1.24-8.87). The outcome was similar in the two groups (OR 2.64; CI 0.27-25.89). G3P[8] was the most common type genotype isolated in 13 (28.89%) patients followed by G2P[4] in 7 (15.56%) patients. Thirteen patients (28.89%) had mixed genotype.

Conclusion: Rotavirus diarrhea was most common below two years of age. G3P[8] was the most common genotype identified.
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http://dx.doi.org/10.1007/s12098-020-03625-0DOI Listing
March 2021

Early postnatal color Doppler changes in neonates receiving delivery room resuscitation with low 5 min Apgar score-a pilot study.

J Perinatol 2021 Mar 9;41(3):486-493. Epub 2020 Dec 9.

Departments of Radiodiagnosis and Imaging, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Aims And Objectives: To evaluate the Doppler changes in the intracranial arteries of neonates exposed to perinatal hypoxic insult and compare it with normal neonates.

Materials And Methods: Color Doppler of bilateral anterior and middle cerebral arteries was performed within 6 h of birth in 26 healthy neonates and 50 neonates who received delivery room resuscitation (DRR) for perinatal depression and had a 5 min Apgar score <7. Comparisons of resistive index (RI) and peak systolic velocity (PSV) were made between the (a) control group (b) patients with low 5 min Apgar score <7 who without clinical features of neonatal encephalopathy at 24 h (c) neonates with perinatal depression with a clinical evidence of disturbed neurological function at 24 h of birth and examination consistent with mild, moderate, or severe encephalopathy using modified Sarnat and Sarnat's classification.

Results: Significantly higher RI was observed in the neonates with to perinatal depression compared to the normal neonates. Significantly higher RI was seen in the patients with clinical features of neonatal encephalopathy (Group C) compared to group B. RI <0.6 and >0.82 was associated with severe neonatal encephalopathy. Differences in PSV were not statistically significant in the various groups.

Conclusion: The study presents the changes in early cerebral Doppler parameters observed in neonates with low 5 min Apgar score following DRR compared to the normal neonates. We also present the relations of Doppler parameters with increasing severity of neonatal encephalopathy according to Sarnat classification.
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http://dx.doi.org/10.1038/s41372-020-00882-xDOI Listing
March 2021

Bone Mineral Metabolism During Chemotherapy in Childhood Acute Lymphoblastic Leukemia.

J Pediatr Hematol Oncol 2020 Aug 18. Epub 2020 Aug 18.

Departments of Pediatrics.

Objective: The aim of this study was to evaluate levels of vitamin D, bone mineral density (BMD), and x-ray features at diagnosis and after 6 months of chemotherapy in patients with acute lymphoblastic leukemia (ALL). Vitamin D levels were also correlated with BMD and x-ray features.

Materials And Methods: 25-Hydroxy vitamin D [25(OH)D] levels, BMD, and x-ray features were assessed in 50 newly diagnosed patients of ALL in the age group of 2 to 14 years. A total of 30 age-matched and sex-matched children were recruited as controls. Vitamin D deficiency was defined as 25(OH)D <10 ng/mL, Vitamin D insufficiency as 10 to 29 ng/mL, and Vitamin D sufficiency as ≥30 ng/mL. Enzyme immunoassay (EIA) was used for the quantitative measurement of 25(OH)D levels in plasma and a LUNAR DPX NT bone densitometer was used for the assessment of BMD.

Results: The mean age of the patients was 6.3 years, with a male:female ratio of 1.38:1. The mean 25(OH)D levels were 31.90±16.90 ng/mL in patients at diagnosis against 41.63±20.50 ng/mL in controls (P=0.02). Levels were 18.50±11.10 ng/mL postchemotherapy (P=0.00). Female sex was a risk factor for deficient 25(OH)D levels. There was a significant decrease in BMD postchemotherapy in the age groups of 5 to 10 and above 10 years at the femoral neck. Osteopenic changes were observed in more number of patients after 6 months of chemotherapy. There was a significant correlation between vitamin D levels, BMD, and osteopenic changes.

Conclusions: Vitamin D deficiency was common among ALL patients, which worsened after chemotherapy. This had a significant correlation with BMD and osteopenic changes in x-ray.
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http://dx.doi.org/10.1097/MPH.0000000000001908DOI Listing
August 2020

Global Retinoblastoma Presentation and Analysis by National Income Level.

JAMA Oncol 2020 05;6(5):685-695

Imam Hussein Cancer Center, Karbala, Iraq.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.

Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.

Design, Setting, And Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.

Main Outcomes And Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.

Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).

Conclusions And Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
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http://dx.doi.org/10.1001/jamaoncol.2019.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047856PMC
May 2020

Structured MRI reporting in spinal dysraphism.

Acta Radiol 2020 Nov 13;61(11):1520-1533. Epub 2020 Feb 13.

Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Magnetic resonance evaluation of spinal dysraphism can be confusing for inexperienced radiologists and a detailed, step-by-step evaluation of the normal and abnormal imaging findings can help garner the diagnosis. The purpose of this article is to review the existing literature and to provide a comprehensive, structured, template checklist-style format for reporting spinal dysraphism that can help inexperienced radiologists to systematically analyze and report all the significant and ancillary findings in cases of spinal dysraphism and efficiently communicate the findings to the treating physician/surgeon.
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http://dx.doi.org/10.1177/0284185120903445DOI Listing
November 2020

Relation Between Cardiac T2* Values and Electrocardiographic Parameters in Children With Transfusion-dependent Thalassemia.

J Pediatr Hematol Oncol 2020 10;42(7):e610-e614

Departments of Pediatrics, Division of Pediatric Hematology Oncology.

Background/objectives: Cardiac T2* magnetic resonance imaging (MRI) is the gold standard to determine myocardial iron overload. As availability of Cardiac T2* is not uniform across developing nations, our strategy was to identify a more accessible and cost effective tool to assess myocardial iron accumulation. As children with transfusion-dependent thalassemia also experience various electrocardiographic abnormalities, we performed electrocardiography (ECG) as well as Cardiac T2* MRI on all children registered in our thalassemia unit.

Materials And Methods: Forty-eight transfusion-dependent thalassemia children with transfusion burden ≥12 times/y (6 to 19 y) in the Thalassemia Unit of the Division of Hematology Oncology, Department of Pediatrics were enrolled. Patients were divided into 3 groups based on severity of T2* value, that is group I (T2*<10), group II (T2* 10 to 20), group III (T2*>20). A T2* value >20 was taken as normal. ECG and serum ferritin was also performed on the day of MRI.

Results: Among the various ECG parameters, QRS duration, and QTc interval were significantly increased if cardiac iron overload was high with a P-value of 0.036 and 0.000, respectively. Also, high serum ferritin predicted a decline in T2* value with a P-value of 0.001. QT interval and QTc interval significantly correlated inversely with T2* (P=0.042, r=-0.295 and P=0.002, r=-0.446, respectively) but not QRS duration (P=0.05, r=-0.282). Serum ferritin also was found to have a significant inverse correlation with T2* value (P=0.000, r=-0.497).

Conclusions: Abnormalities on ECG, that is prolongation of QRS duration, QT interval, and QTc interval were significantly associated with cardiac iron overload, that is decrease in the value of Cardiac T2* in our study.
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http://dx.doi.org/10.1097/MPH.0000000000001734DOI Listing
October 2020

Variable Phenotypic Presentation of Two Siblings with Hemoglobin SD Disease.

Indian J Pediatr 2020 03 14;87(3):229-230. Epub 2020 Jan 14.

Division of Hematology-Oncology, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

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http://dx.doi.org/10.1007/s12098-019-03168-zDOI Listing
March 2020

Edwardsiella induces microtubule-severing in host epithelial cells.

Microbiol Res 2019 Dec 26;229:126325. Epub 2019 Aug 26.

Guangdong Technion, Israel Institute of Technology, Shantou, Guangdong, China. Electronic address:

Edwardsiella bacteria cause economic losses to a variety of commercially important fish globally. Human infections are rare and result in a gastroenteritis-like illness. Because these bacteria are evolutionarily related to other Enterobacteriaceae and the host cytoskeleton is a common target of enterics, we hypothesized that Edwardsiella may cause similar phenotypes. Here we use HeLa and Caco-2 infection models to show that microtubules are severed during the late infections. This microtubule alteration phenotype was not dependant on the type III or type VI secretion system (T3SS and T6SS) of the bacteria as ΔT3SS and ΔT6SS mutants of E. piscicida EIB202 and E. tarda ATCC15947 that lacks both also caused microtubule disassembly. Immunolocalization experiments showed the host katanin catalytic subunits A1 and A like 1 proteins at regions of microtubule severing, suggesting their involvement in the microtubule disassembly events. To identify bacterial components involved in this phenotype, we screened a 2,758 transposon library of E. piscicida EIB202 and found that 4 single mutations in the atpFHAGDC operon disrupted microtubule disassembly in HeLa cells. We then constructed three atp deletion mutants; they all could not disassemble host microtubules. This work provides the first clear evidence of host cytoskeletal alterations during Edwardsiella infections.
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http://dx.doi.org/10.1016/j.micres.2019.126325DOI Listing
December 2019

Langerhans cell histiocytosis: An enigmatic disease.

South Asian J Cancer 2019 Jul-Sep;8(3):183-185

Department of Pediatrics, Division of Hematology-Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Background: Langerhans cell histiocytosis (LCH) is a poorly understood disease with heterogeneous clinical presentation ranging from unifocal bony involvement to disseminated disease with life-threatening complications.

Materials And Methods: The clinical profile, laboratory findings, treatment, and long-term outcome were retrieved from maintained medical records from January 2006 to January 2016 and were retrospectively analyzed. The extent of the disease was classified as per the LCH-III trial of "The Histiocyte Society." The assessment and categorization of treatment response followed LCH III trial definitions.

Results: A total of 28 children with LCH were diagnosed. The age ranged between 5 months and 9 years, with a mean of 3½ years. The M: F ratio was 3:1. Single system, unifocal and multifocal bone diseases were seen in nine (32.1%) and two (7.1%) cases, respectively. Disseminated disease without risk organ involvement was seen in six (21.1%), whereas disseminated disease with risk organ involvement was seen in 11 (39.3%) cases. The most common presentation was bony involvement (19 [67.8%]), out of which 16 (88.8%) had skull involvement. During follow-up, 17 (60.7%) were in complete remission though five (17.8%) of them relapsed, but achieved second remission. Two (7.1%) were lost to follow-up. Six (21.4%) had progressive disease of which four expired and two abandoned treatment. Two (10.7%) refused the initiation of treatment.

Conclusion: A better understanding of the disease, early suspicion, and diagnosis can improve the outcome of patients with LCH.
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http://dx.doi.org/10.4103/sajc.sajc_211_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699242PMC
September 2019

Design of therapeutically improved analogue of the antimicrobial peptide, indolicidin, using a glycosylation strategy.

Amino Acids 2019 Nov 4;51(10-12):1443-1460. Epub 2019 Sep 4.

National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India.

Indolicidin is a member of cathelicidin family which displays broad spectrum antimicrobial activity. Severe toxicity and aggregation propensity associated with indolicidin pose a huge limitation to its probable therapeutic application. We are reporting the use of glycosylation strategy to design an analogue of indolicidin and subsequently explore structural and functional effects of sugar on it. Our study led to the design of a potent antibacterial glycosylated peptide, [βGlc-T9,K7]indolicidin, which showed decreased toxicity against erythrocytes and macrophage cells and thus a higher therapeutic selectivity. The incorporation of sugar also increased the solubility of the peptide. The mode of bacterial killing, functional stability, LPS binding, and cytokine inhibitory potential of the peptide, however, seemed unaffected upon glycosylation. Absence of significant changes in structure upon glycosylation accounts for the possibly retained functions and mode of action of the peptide. Our report thus presents the designing of an indolicidin analogue with improved therapeutic potential by substituting aromatic amino acid with glycosylated amino acid as a promising strategy for the first time.
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http://dx.doi.org/10.1007/s00726-019-02779-2DOI Listing
November 2019

A Rare Case of Multiple Intracranial Cysts.

Indian J Pediatr 2019 12 27;86(12):1162-1163. Epub 2019 Jun 27.

Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

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http://dx.doi.org/10.1007/s12098-019-03008-0DOI Listing
December 2019

Cardiac T2* magnetic resonance analysis of membranous interventricular septum in assessment of cardiac iron overload in pediatric thalassemia patients: A pilot study.

Indian J Radiol Imaging 2019 Jan-Mar;29(1):33-39

Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Background: Cardiac iron deposition in transfusion-dependent thalassemia patients is patchy in distribution.

Purpose: The purpose of this study is to assess the correlation between T2* matrices of membranous interventricular septum (MIVS) and T2* values of muscular interventricular septum (IVS) on magnetic resonance imaging (MRI) and to evaluate the relationship of myocardial T2* at these two locations with MRI-estimated liver iron concentrations (LIC) and electrocardiographic (ECG) parameters.

Material And Methods: MRI of heart and liver was performed in 16 consecutive pediatric patients of transfusion-dependent thalassemia major to calculate liver iron concentration and T2* time of membranous and muscular IVS. ECG parameters of these patients were charted and correlated with MRI parameters.

Results: No significant correlation between T2* values of muscular IVS and MIVS was observed. Mean T2* of MIVS (9.8 ms) was significantly lower than that of muscular IVS (26.9 ms). T2* of MIVS correlated strongly with LIC where as a weak correlation was observed between T2* of IVS and LIC. Significantly higher mean QTc (corrected QT interval) value (439.86 ms) was seen in patients with T2* IVS <20 ms.

Conclusion: Addition of T2* analysis of MIVS to the existing MRI protocol, consisting of muscular IVS analysis, may offer a more sensitive estimation of cardiac iron overload.
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http://dx.doi.org/10.4103/ijri.IJRI_395_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467041PMC
April 2019

Posterior quadrantic dysplasia with localized hemimegalencephaly in a patient with giant congenital melanocytic nevus: First case report.

Neuroradiol J 2019 Jun 22;32(3):210-214. Epub 2019 Feb 22.

2 Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, India.

Giant congenital melanocytic nevus (GCMN) is associated with neurocutaneous melanocytosis and various other neurological complications. Its association with migrational anomalies of the brain is extremely rare. Herein, we document the first case of GCMN in a one-day-old baby associated with localized hemimegalencephaly (HME) of the brain with extensive malformation of cortical development including polymicrogyria, pachygyria and sublobar dysplasia, limited to an enlarged quadrant of the brain. HME and GCMN are considered embryological anomalies of cell migration and proliferation. We discuss the unusual magnetic resonance imaging findings along with a brief review of the literature. To the best of our knowledge, our case is the first to report the association of GCMN with localized HME.
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http://dx.doi.org/10.1177/1971400919832474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512208PMC
June 2019

Strongly Correlated Excitons of Regular/Irregular Planar Quantum Dots in Magnetic Field: Size-Extensive Bi- and Triexciton (e-h-e-h and e-e-h/e-h-h) Systems by Multipole Expansion.

ACS Omega 2017 Oct 31;2(10):7410-7423. Epub 2017 Oct 31.

Department of Chemistry (Physical), University of Delhi, Vishwavidyalaya Marg, North Campus, 110 007 New Delhi, India.

Excitons in parabolically confined planar quantum dots with a transverse magnetic field have been studied in various model systems. The correlations between e-h, e-e, and h-h have been incorporated in terms of exact, simply elegant, and absolutely terminating finite summed Lauricella functions which eliminate the secular divergence problem and pave way for a comprehensive understanding of certain exotic phenomena of various two-dimensional regular and irregular quantum dots. A simple yet highly accurate and exact variational wave function in terms of Whittaker- function extensible to multiexcitonic systems has been propounded. We have also presented a formulation extending the size of the systems to triexcitonic (e-e-h/e-h-h), biexcitonic (e-h-e-h), and multiexcitonic ("N" e-h pair) planar dots by mono-, di-, quadru-, and octopole expansions. As a benchmark, we have examined the energy spectra, level-spacing statistics, heat capacities ( at 1 K), and magnetization ( ≈ 0-1 K) of He/SiO/BN/GaAs model systems for different lateral confinements, magnetic fields, mass ratios of e-h, and dielectric constants (ϵ).
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http://dx.doi.org/10.1021/acsomega.7b00886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645354PMC
October 2017

Exploring Heme and Hemoglobin Binding Regions of Plasmodium Heme Detoxification Protein for New Antimalarial Discovery.

J Med Chem 2017 10 11;60(20):8298-8308. Epub 2017 Oct 11.

Malaria Biology Group, International Centre for Genetic Engineering and Biotechnology , Aruna Asaf Ali Marg, New Delhi 110067, India.

Hemoglobin degradation/hemozoin formation, essential steps in the Plasmodium life cycle, are targets of existing antimalarials. The pathway still offers vast possibilities to be explored for new antimalarial discoveries. Here, we characterize heme detoxification protein, PfHDP, a major protein involved in hemozoin formation, as a novel drug target. Using in silico and biochemical approaches, we identified two heme binding sites and a hemoglobin binding site in PfHDP. Treatment of Plasmodium falciparum 3D7 parasites with peptide corresponding to the hemoglobin binding domain in PfHDP resulted in food vacuole abnormalities similar to that seen with a cysteine protease inhibitor, E-64 (I-1). Screening of compounds that bound the modeled PfHDP structure in the heme/hemoglobin-binding pockets from Maybridge Screening Collection identified a compound, ML-2, that inhibited parasite growth in a dose-dependent manner, thus paving the way for testing its potential as a new drug candidate. These results provide functional insights into the role of PfHDP in Hz formation and further suggest that PfHDP could be an important drug target to combat malaria.
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http://dx.doi.org/10.1021/acs.jmedchem.7b00089DOI Listing
October 2017

Electron Spin Relaxation and Biochemical Characterization of the Hydrogenase Maturase HydF: Insights into [2Fe-2S] and [4Fe-4S] Cluster Communication and Hydrogenase Activation.

Biochemistry 2017 06 13;56(25):3234-3247. Epub 2017 Jun 13.

Department of Chemistry and Biochemistry, Montana State University , Bozeman, Montana 59717, United States.

Nature utilizes [FeFe]-hydrogenase enzymes to catalyze the interconversion between H and protons and electrons. Catalysis occurs at the H-cluster, a carbon monoxide-, cyanide-, and dithiomethylamine-coordinated 2Fe subcluster bridged via a cysteine to a [4Fe-4S] cluster. Biosynthesis of this unique metallocofactor is accomplished by three maturase enzymes denoted HydE, HydF, and HydG. HydE and HydG belong to the radical S-adenosylmethionine superfamily of enzymes and synthesize the nonprotein ligands of the H-cluster. These enzymes interact with HydF, a GTPase that acts as a scaffold or carrier protein during 2Fe subcluster assembly. Prior characterization of HydF demonstrated the protein exists in both dimeric and tetrameric states and coordinates both [4Fe-4S] and [2Fe-2S] clusters [Shepard, E. M., Byer, A. S., Betz, J. N., Peters, J. W., and Broderick, J. B. (2016) Biochemistry 55, 3514-3527]. Herein, electron paramagnetic resonance (EPR) is utilized to characterize the [2Fe-2S] and [4Fe-4S] clusters bound to HydF. Examination of spin relaxation times using pulsed EPR in HydF samples exhibiting both [4Fe-4S] and [2Fe-2S] cluster EPR signals supports a model in which the two cluster types either are bound to widely separated sites on HydF or are not simultaneously bound to a single HydF species. Gel filtration chromatographic analyses of HydF spectroscopic samples strongly suggest the [2Fe-2S] and [4Fe-4S] clusters are coordinated to the dimeric form of the protein. Lastly, we examined the 2Fe subcluster-loaded form of HydF and showed the dimeric state is responsible for [FeFe]-hydrogenase activation. Together, the results indicate a specific role for the HydF dimer in the H-cluster biosynthesis pathway.
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http://dx.doi.org/10.1021/acs.biochem.7b00169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5490485PMC
June 2017

Do Not Forget to Look at the Big Toe.

Indian J Pediatr 2017 12 13;84(12):965-966. Epub 2017 May 13.

Department of Pediatrics, Genetic Clinic, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.

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http://dx.doi.org/10.1007/s12098-017-2364-7DOI Listing
December 2017

Congenital facial nerve aplasia: MR depiction of a rare anomaly.

Indian J Radiol Imaging 2016 Oct-Dec;26(4):517-520

Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

We report two infants presenting with unilateral congenital facial palsy since birth. Magnetic resonance imaging (MRI) in both the cases revealed complete unilateral aplasia of facial nerve. To our knowledge, this is the first reported MR depiction of nonsyndromic isolated facial nerve aplasia. Imaging features and the pertinent anatomy is discussed along with a brief review of literature.
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http://dx.doi.org/10.4103/0971-3026.195791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201086PMC
January 2017

Magnetic resonance neurographic confirmation of extensive Plexiform neurofibroma in neurofibromatosis-1 presenting as ambiguous genitalia.

Indian J Radiol Imaging 2016 Jul-Sep;26(3):332-336

Department of Radiodiagnosis, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Genitourinary involvement of neurofibromatosis is uncommon and genital neurofibromatosis is even rarer. Involvement of clitoris by neurofibroma can lead to clitoromegaly masquerading as a male penis. We report such a case of ambiguous genitalia in a 7-year-old female child presenting with clitoromegaly since birth, in which magnetic resonance imaging (MRI) revealed the presence of extensive neurofibromatosis in the clitoris and lumbosacral regions. We emphasize the central role of MRI in evaluation of hormonal and non-hormonal causes of ambiguous genitalia. We further discuss the merits of including MR neurography in the imaging protocol for comprehensive delineation of neurofibromatosis.
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http://dx.doi.org/10.4103/0971-3026.190423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5036330PMC
November 2016

Comparison of Continuous Wave and Rapid Scan X-band Electron Paramagnetic Resonance of Irradiated Clipped Fingernails.

Radiat Prot Dosimetry 2016 Dec 2;172(1-3):133-138. Epub 2016 Sep 2.

Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208 USA

X-band rapid scan electron paramagnetic resonance (EPR) measures the free radicals in irradiated clipped fingernails with higher signal-to-noise (S/N) and lower standard deviation of the signal amplitude for replicate measurements than does conventional continuous wave (CW) EPR in the same measurement time. For a clipped fingernail sample irradiated to 10 Gy and data acquisition time of 30 s with B = 8.5 μT, the S/N for rapid scan is >2000 for the absorption spectrum and 1200 for the corresponding first derivative. The standard deviation for replicate measurements of signal amplitude is ~1%. For CW spectra, the S/N depends on the modulation amplitude. The CW signal has a first derivative peak-to-peak linewidth of 0.95 mT. For 30 s of CW acquisition time, the S/N was 30 for a conservative modulation amplitude of 0.2 mT and B of 2.3 μT or 90 for a modulation amplitude of 0.4 mT and B of 3.2 μT, which resulted in standard deviations of replicate measurements of 5% or 2%, respectively.
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http://dx.doi.org/10.1093/rpd/ncw162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225971PMC
December 2016

Mycofactocin biosynthesis: modification of the peptide MftA by the radical S-adenosylmethionine protein MftC.

FEBS Lett 2016 08 29;590(16):2538-48. Epub 2016 Jun 29.

Department of Chemistry and Biochemistry, University of Denver, CO, USA.

Mycofactocin is a putative, peptide derived, cofactor that is associated primarily with the Mycobacterium genera including the pathogen M. tuberculosis. The pathway consists of the three genes mftA, mftB, and mftC that encode for the peptide substrate, peptide chaperone, and a radical S-adenosylmethionine protein (RS), respectively. Here, we show that the MftB acts as a peptide chaperone, binding MftA with a submicromolar KD (~ 100 nm) and MftC with a low micromolar KD (~ 2 μm). Moreover, we demonstrate that MftC is a radical S-adenosylmethionine (SAM) enzyme. Finally, we show that MftC catalyzes the oxidative decarboxylation of the peptide MftA.
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http://dx.doi.org/10.1002/1873-3468.12249DOI Listing
August 2016

Magnetic resonance spectroscopy - Revisiting the biochemical and molecular milieu of brain tumors.

BBA Clin 2016 Jun 12;5:170-8. Epub 2016 Apr 12.

Consultant Radiologist.

Background: Magnetic resonance spectroscopy (MRS) is an established tool for in-vivo evaluation of the biochemical basis of human diseases. On one hand, such lucid depiction of 'live biochemistry' helps one to decipher the true nature of the pathology while on the other hand one can track the response to therapy at sub-cellular level. Brain tumors have been an area of continuous interrogation and instigation for mankind. Evaluation of these lesions by MRS plays a crucial role in the two aspects of disease management described above.

Scope Of Review: Presented is an overview of the window provided by MRS into the biochemical aspects of brain tumors. We systematically visit each metabolite deciphered by MRS and discuss the role of deconvoluting the biochemical aspects of pathologies (here in context of brain tumors) in the disease management cycle. We further try to unify a radiologist's perspective of disease with that of a biochemist to prove the point that preclinical work is the mother of the treatment we provide at bedside as clinicians. Furthermore, an integrated approach by various scientific experts help resolve a query encountered in everyday practice.

Major Conclusions: MR spectroscopy is an integral tool for evaluation and systematic follow-up of brain tumors. A deeper understanding of this technology by a biochemist would help in a swift and more logical development of the technique while a close collaboration with radiologist would enable definitive application of the same.

General Significance: The review aims at inciting closer ties between the two specialists enabling a deeper understanding of this valuable technology.
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http://dx.doi.org/10.1016/j.bbacli.2016.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845155PMC
June 2016

Low-dose maternal warfarin intake resulting in fetal warfarin syndrome: In search for a safe anticoagulant regimen during pregnancy.

Birth Defects Res A Clin Mol Teratol 2016 Feb 21;106(2):142-7. Epub 2015 Sep 21.

Neonatology Unit, Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

Background: Fetal exposure to maternal ingestion of warfarin is known to produce certain dysmorphic features in the neonate, known as fetal warfarin syndrome (FWS). There is a general consensus that maternal intake of warfarin at a daily dose of 5 mg or less is safe both for the infant and the mother.

Methods: We report four cases of FWS born to mothers with rheumatic heart disease on warfarin prophylaxis during pregnancy at a dose less than 5 mg/day.

Results: Along with typical facial features of FWS and multiple epiphyseal stippling in skeletal x-ray, Case 1 had Dandy-Walker malformation and Case 2 had laryngo-tracheomalacia and patent ductus arteriosus.

Conclusion: We emphasize the need for optimizing the choice and dosage schedule of anticoagulants during pregnancy, least harmful for the mother and her developing fetus.
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http://dx.doi.org/10.1002/bdra.23435DOI Listing
February 2016

Gadolinium-Loaded Viral Capsids as Magnetic Resonance Imaging Contrast Agents.

Appl Magn Reson 2015 Mar 11;46(3):349-355. Epub 2015 Jan 11.

Department of Chemistry, Indiana University, Bloomington, IN 47405, USA.

Polymeric nanohybrid P22 virus capsids were used as templates for high density Gd loading to explore magnetic field-dependent (0.5-7.0 T) proton relaxivity. The field-dependence of relaxivity by the spatially constrained Gd in the capsids was similar when either the loading of the capsids or the concentration of capsids was varied. The ionic longitudinal relaxivity, , decreased from 25-32 mM s at 0.5 T to 6-10 mM s at 7 T. The ionic transverse relaxivity, , increased from 28-37 mM s at 0.5 T to 39-50 mM s at 7 T. The / ratio increased linearly with increasing magnetic field from about 1 at 0.5 T, which is typical of contrast agents, to 5-8 at 7 T, which is approaching the ratios for contrast agents. Increases in electron paramagnetic resonance line widths at 80 and 150 K and higher microwave powers required for signal saturation indicate enhanced Gd electron spin relaxation rates for the Gd-loaded capsids than for low concentration Gd. The largest / at 7 T was for the highest cage loading, which suggests that Gd-Gd interactions within the capsid enhance more than .
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http://dx.doi.org/10.1007/s00723-014-0639-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645056PMC
March 2015

An enhanced MEMS error modeling approach based on Nu-Support Vector Regression.

Sensors (Basel) 2012 9;12(7):9448-66. Epub 2012 Jul 9.

EECS Department, The University of Toledo, MS 308, 2801 W. Bancroft St., Toledo, OH 43606, USA.

Micro Electro Mechanical System (MEMS)-based inertial sensors have made possible the development of a civilian land vehicle navigation system by offering a low-cost solution. However, the accurate modeling of the MEMS sensor errors is one of the most challenging tasks in the design of low-cost navigation systems. These sensors exhibit significant errors like biases, drift, noises; which are negligible for higher grade units. Different conventional techniques utilizing the Gauss Markov model and neural network method have been previously utilized to model the errors. However, Gauss Markov model works unsatisfactorily in the case of MEMS units due to the presence of high inherent sensor errors. On the other hand, modeling the random drift utilizing Neural Network (NN) is time consuming, thereby affecting its real-time implementation. We overcome these existing drawbacks by developing an enhanced Support Vector Machine (SVM) based error model. Unlike NN, SVMs do not suffer from local minimisation or over-fitting problems and delivers a reliable global solution. Experimental results proved that the proposed SVM approach reduced the noise standard deviation by 10-35% for gyroscopes and 61-76% for accelerometers. Further, positional error drifts under static conditions improved by 41% and 80% in comparison to NN and GM approaches.
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http://dx.doi.org/10.3390/s120709448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444110PMC
February 2013

Waist circumference measurement by site, posture, respiratory phase, and meal time: implications for methodology.

Obesity (Silver Spring) 2009 May 22;17(5):1056-61. Epub 2009 Jan 22.

Department of Epidemiology, University of North Carolina at Chapel Hill, North Carolina, USA.

Waist circumference (WC) has been advocated as a simple, reliable, and cost-effective measure to understand an individual's cardio-metabolic risk. Although several protocols exist for measuring WC, the variation induced by a few factors has not been investigated. We compared several established and experimental WC measurement protocols to identify factors that may cause variations in WC measurement. In this cross-sectional study, we examined the variations in the measurement of waist circumference (WC) measures carried out in 11 ways differing by anatomical site, posture, respiratory phase, and time since last meal, using repeated measure analysis of variance (using mixed models) after Tukey-Kramer adjustment. We estimated the proportion of variance in percentage of body fat (%BF) and fat-free mass (FFM) explained by each of the WC measures. We studied 123 apparently healthy Asian Indians (75 females), with mean (s.d.) age of 34 (8.7) years and BMI of 23.9 (4.8) kg/m(2). Overall, the mean of WCs measured using the 11 protocols were statistically different. Further, post hoc analysis showed statistically significant, yet mostly small, differences between most of the pairs. No single WC measure explained highest variance in %BF or FFM for both genders. Although, the National Institute of Health (NIH), USA, protocol was convenient and may be less prone to errors, at present it does not control for many variables tested in this study. Measures of WC measured using different protocols were statistically different. We suggest that the site of measurement, posture, phase of respiration, and time since last meal should be standardized for the development of a protocol for measurement of WC for worldwide use.
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http://dx.doi.org/10.1038/oby.2008.635DOI Listing
May 2009