Publications by authors named "Ankit Verma"

93 Publications

Novel genetic variants of KHDC3L and other members of the subcortical maternal complex associated with Beckwith-Wiedemann syndrome or Pseudohypoparathyroidism 1B and multi-locus imprinting disturbances.

Clin Epigenetics 2022 05 28;14(1):71. Epub 2022 May 28.

Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Università Degli Studi Della Campania "Luigi Vanvitelli", Caserta, Italy.

Background: Beckwith-Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively. In both of these diseases a subset of the patients is affected by multi-locus imprinting disturbances (MLID). In several families, MLID is associated with damaging variants of maternal-effect genes encoding protein components of the subcortical maternal complex (SCMC). However, frequency, penetrance and recurrence risks of these variants are still undefined. In this study, we screened two cohorts of BWS patients and one cohort of PHP1B patients for the presence of MLID, and analysed the positive cases for the presence of maternal variants in the SCMC genes by whole exome-sequencing and in silico functional studies.

Results: We identified 10 new cases of MLID associated with the clinical features of either BWS or PHP1B, in which segregate 13 maternal putatively damaging missense variants of the SCMC genes. The affected genes also included KHDC3L that has not been associated with MLID to date. Moreover, we highlight the possible relevance of relatively common variants in the aetiology of MLID.

Conclusion: Our data further add to the list of the SCMC components and maternal variants that are involved in MLID, as well as of the associated clinical phenotypes. Also, we propose that in addition to rare variants, common variants may play a role in the aetiology of MLID and imprinting disorders by exerting an additive effect in combination with rarer putatively damaging variants. These findings provide useful information for the molecular diagnosis and recurrence risk evaluation of MLID-associated IDs in genetic counselling.
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http://dx.doi.org/10.1186/s13148-022-01292-wDOI Listing
May 2022

A Hyperalert Newborn.

Neoreviews 2022 Jun;23(6):e413-e415

Departments of *Pediatrics and.

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http://dx.doi.org/10.1542/neo.23-6-e413DOI Listing
June 2022

A novel generalized fuzzy intelligence-based ant lion optimization for internet of things based disease prediction and diagnosis.

Cluster Comput 2022 Feb 24:1-16. Epub 2022 Feb 24.

Department of Computer Science, Invertis University, Uttar Pradesh, Bareilly, 243123 India.

In the modern healthcare system, the function of the Internet of Things (IoT) and the data mining methods with cloud computing plays an essential role in controlling a large number of big data for predicting and diagnosing various categories of diseases. However, when the patients suffer from more than one disease, the physician may not identify it properly. Therefore, in this research, the predictive method using the cloud with IoT-based database is proposed for forecasting the diseases that utilized the biosensors to estimate the constraints of patients. In addition, a novel Generalized Fuzzy Intelligence-based Ant Lion Optimization (GFIbALO) classifier along with a regression rule is proposed for predicting the diseases accurately. Initially, the dataset is filtered and feature extracted using the regression rule that data is processed on the proposed GFIbALO approach for classifying diseases. Moreover, suppose the patient has been affected by any diseases, in that case, the warning signal will be alerted to the patients via text or any other way, and the patients can get advice from doctors or any other medical support. The implementation of the proposed GFIbALO classifier is done with the use of the MATLAB tool. Subsequently, the results from the presented model are compared with state of the art techniques, and it shows that the presented method is more beneficial in diagnosis and disease forecast.
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http://dx.doi.org/10.1007/s10586-022-03565-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868039PMC
February 2022

Bentonite-based sodium alginate/ dextrin cross-linked poly (acrylic acid) hydrogel nanohybrids for facile removal of paraquat herbicide from aqueous solutions.

Chemosphere 2022 Mar 26;291(Pt 3):133002. Epub 2021 Nov 26.

Biorefining and Advanced Materials Research Center, SRUC, EH9 3JG, UK; Department of Mechanical Engineering, School of Engineering, Shiv Nadar University, Uttar Pradesh, 201314, India; School of Engineering, University of Petroleum & Energy Studies (UPES), Dehradun, 248007, Uttarakhand, India. Electronic address:

Removal of hazardous herbicides from the aqueous solution is critical for overcoming health-related issues across the wider population. In the current work, we have prepared sodium alginate (SAlg), dextrin, and acrylic acid (AA) based cross-linked hydrogels, composed of bentonite incorporated in the biocompatible hydrogel matrix. This hydrogel composite can remove highly toxic herbicide paraquat (PQ). As-synthesised hydrogel (SAlg/dextrin-cl-PAA) and hydrogel composite (SAlg/dextrin-cl-PAA/bentonite) were further analysed by infra-red spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and thermogravimetric analysis (TGA/DSC). For the first time, PQ adsorption onto sodium and dextrin-based hydrogel was also evaluated. The measured highest removal capacities were 76.923 and 90.909 mg g for the SAlg/dextrin-cl-PAA and SAlg/dextrin-cl-PAA/bentonite, respectively. Pseudo-second-order (PSO) and Langmuir isotherm models have shown to be best suited for accurately describing the adsorption mechanism. A thermodynamics study verified that the adsorption of PQ on adsorbents is spontaneous, favourable and exothermic. Moreover, reusability analysis shows that the adsorbents possess good reproducibility even after six successive cycles. The adsorption results demonstrate that the synthesised adsorbents are very efficient for removing herbicides (PQ) from wastewater.
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http://dx.doi.org/10.1016/j.chemosphere.2021.133002DOI Listing
March 2022

Prenatal Pericardiocentesis and Postnatal Sirolimus for a Giant Inoperable Cardiac Rhabdomyoma.

JACC Case Rep 2021 Oct 6;3(13):1473-1479. Epub 2021 Oct 6.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.

We describe the case of an antenatally diagnosed massive cardiac tumor in a fetus requiring cardiorespiratory support immediately following birth. We further discuss the successful management of this case and highlight the importance of a multidisciplinary team in managing such complicated cases. ().
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http://dx.doi.org/10.1016/j.jaccas.2021.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551506PMC
October 2021

Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs.

Sci Rep 2021 07 5;11(1):13802. Epub 2021 Jul 5.

Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Università degli Studi della Campania "Luigi Vanvitelli", 81100, Caserta, Italy.

ZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and imprinted gene expression is lacking. To address the latter issue, we differentiated wild-type and Zfp57 hybrid mouse ESCs into neural precursor cells (NPCs) and evaluated allelic expression of imprinted genes. In mutant NPCs, we observed a reduction of allelic bias of all the 32 genes that were imprinted in wild-type cells, demonstrating that ZFP57-dependent methylation is required for maintaining or acquiring imprinted gene expression during differentiation. Analysis of expression levels showed that imprinted genes expressed from the non-methylated chromosome were generally up-regulated, and those expressed from the methylated chromosome were down-regulated in mutant cells. However, expression levels of several imprinted genes acquiring biallelic expression were not affected, suggesting the existence of compensatory mechanisms that control their RNA level. Since neural differentiation was partially impaired in Zfp57-mutant cells, this study also indicates that imprinted genes and/or non-imprinted ZFP57-target genes are required for proper neurogenesis in cultured ESCs.
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http://dx.doi.org/10.1038/s41598-021-93297-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257706PMC
July 2021

The role of the mitochondrial protein VDAC1 in inflammatory bowel disease: a potential therapeutic target.

Mol Ther 2022 02 2;30(2):726-744. Epub 2021 Jul 2.

Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. Electronic address:

Recent studies have implicated mitochondrial dysfunction as a trigger of inflammatory bowel diseases, including Crohn's disease (CD) and ulcerative colitis (UC). We have investigated the role of the mitochondria gate-keeper protein, the voltage-dependent-anion channel 1 (VDAC1), in gastrointestinal inflammation and tested the effects of the newly developed VDAC1-interacting molecules, VBIT-4 and VBIT-12, on UC induced by dextran sulfate sodium (DSS) or trinitrobenzene sulphonic acid (TNBS) in mice. VDAC1, which controls metabolism, lipids transport, apoptosis, and inflammasome activation, is overexpressed in the colon of CD and UC patients and DSS-treated mice. VBIT-12 treatment of cultured colon cells inhibited the DSS-induced VDAC1 overexpression, oligomerization, and apoptosis. In the DSS-treated mice, VBIT-12 suppressed weight loss, diarrhea, rectal bleeding, pro-inflammatory cytokine production, crypt and epithelial cell damage, and focal inflammation. VBIT-12 also inhibited the infiltration of inflammatory cells, apoptosis, mtDNA release, and activation of caspase-1 and NRLP3 inflammasome to reduce the inflammatory response. The levels of the ATP-gated PX-Ca/K channel and ER-IP3R-Ca channel, and of the mitochondrial anti-viral protein (MAVS), mediating NLRP3 inflammasome assembly and activation, were highly increased in DSS-treated mice, but not when VBIT-12 treated. We conclude that UC may be promoted by VDAC1-overexpression and may therefore be amenable to treatment with novel VDAC1-interacting molecules. This VDAC1-based strategy exploits a completely new target for UC treatment and opens a new avenue for treating other inflammatory/autoimmune diseases.
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http://dx.doi.org/10.1016/j.ymthe.2021.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821898PMC
February 2022

A comparative study between continuous and interrupted sutures in open pyeloplasty.

Urologia 2021 Nov 19;88(4):292-297. Epub 2021 May 19.

Department of Urology, IPGMER, Kolkata, West Bengal, India.

Background: Pelvi-ureteric junction obstruction (PUJO) is one of the common causes of obstructive uropathy dealt by urologists around the globe. The management of PUJO requires surgical intervention and pelvi-ureteral anastomosis is most time-consuming step in surgery and suturing plays a critical role for the good outcome of the surgery.

Objective: To assess the outcomes of continuous or interrupted suturing in open pyeloplasties done for PUJ obstruction.

Materials And Methods: This comparative study was conducted in the department of Urology in a tertiary care hospital of eastern India. A total of 60 patients with pelviureteric junction obstruction were included as per inclusion and exclusion criteria and divided into two groups depending upon whether continuous (Group A) or interrupted (Group B) suturing was done. Both groups were compared for mean operative time, mean suturing time, duration of post-operative drainage, mean drain output, post-operative hospital stay, postoperative GFR and improvement in GFR.

Results: Out of 60 patients continuous and interrupted suturing was done in 30 patients in both arms. Out of 60 cases there were 46 (76.66%) males and 14 (23.33%) females with a M:F ratio of 1:0.30. The mean age in group A and group B was found to be 30.06 ± 8.28 and 27.63 ± 6.07, respectively. Mean operative time, mean suturing time, duration of post-operative drainage, mean drain output and postoperative hospital stay were found to be higher in interrupted suture group and the difference was found to be statistically highly significant ( < 0.0001). The complication rates and recurrence rates were found comparable in both the cases with no statistically significant difference ( > 0.05).

Conclusion: Continuous suturing technique for pyeloplasty is preferable as it is found to have a lower mean operative time, mean suturing time, duration of post-operative drainage, mean drain output and postoperative hospital stay.
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http://dx.doi.org/10.1177/03915603211015109DOI Listing
November 2021

BF-etherate promoted facile access to vinyloxyimidazopyridines: a metal-free sustainable approach.

Mol Divers 2022 Apr 16;26(2):1259-1266. Epub 2021 May 16.

Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Prayagraj, 211002, India.

A convenient and metal-free synthesis of vinyloxyimidazopyridine derivatives has been attained via BF.OEt promoted one-pot multicomponent approach. This procedure involves a facile coupling of 2-aminopyridine derivatives with arylglyoxal and alkyne derivatives. BF.OEt complexation has successfully catalyzed the reaction at room temperature. Utilization of transition metal-free catalyst, mild reaction conditions, easy handling and operational simplicity are key features of developed process.
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http://dx.doi.org/10.1007/s11030-021-10228-0DOI Listing
April 2022

Neonatal Pneumocephalus Secondary to Acinetobacter Meningitis.

Indian J Pediatr 2021 06 15;88(6):616. Epub 2021 Mar 15.

Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1007/s12098-021-03719-3DOI Listing
June 2021

Improving photocatalytic efficiency of MnFeO ferrites via doping with Zn/La ions: photocatalytic dye degradation for water remediation.

Environ Sci Pollut Res Int 2021 Mar 8. Epub 2021 Mar 8.

Department of Chemistry, ACC Wing, Indian Military Academy, Dehradun, Uttarakhand, 248007, India.

The interference of industrial effluents such as dyes, surfactants, metals, polycyclic aromatic hydrocarbons, and pharmaceutical waste has become a severe global problem for human health due to their carcinogenic, mutagenic, and toxic properties. Ferrites were considered promising photocatalysts for the degradation of organic and inorganic dyes. This study mainly focused on improving the photocatalytic performance of MnFeO nanoferrites via doping of Zn and La ions. The zinc and lanthanum substituted MnZnLaFeO nanoferrites were prepared by the sol-gel auto-combustion technique for the degradation of organic textile malachite green dye (MGD) under the natural solar irradiation. The synthesized nanoferrites were investigated for their structural properties, surface morphology and elemental analysis, optical studies, magnetic properties, and photocatalytic performance by XRD, FESEM/EDX, FTIR/Raman spectrum, vibrating sample magnetometer, and UV-visible spectrophotometer, respectively. The substitution of zinc and lanthanum improved the photocatalytic efficiency of nanoferrites, and about 96% of MGD was degraded by MnZnLaFeO after 60 min of irradiation. The results showed the pseudo-first-order kinetics for dye degradation using undoped and Zn/La-doped MnFeO photocatalysts.
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http://dx.doi.org/10.1007/s11356-021-13147-7DOI Listing
March 2021

Characteristics and outcomes of 231 COVID-19 cases admitted at a tertiary facility in India: An observational cohort study.

J Family Med Prim Care 2020 Dec 31;9(12):6267-6272. Epub 2020 Dec 31.

Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India.

Background: Ongoing pandemic because of COVID-19 has spread across countries, with varied clinical features and severity. Awareness of clinical course among asymptomatic and symptomatology in symptomatic cases is essential for patients' management as well as optimal utilization of health services (in resource limited settings) based on clinical status and risk factors. This study aimed to describe the clinical characteristics and outcomes of patients admitted with COVID-19 illness in the initial phase of the pandemic in India.

Methods: It was an observational study. Patients aged 18 years or more, with confirmed SARS-CoV-2 infection, asymptomatic or mildly ill, were included. Patients with moderate-severe disease at admission or incomplete clinical symptomatology records were excluded. Data regarding demography, comorbidities, clinical features and course, treatment, results of SARS-CoV-2 RT-PCR, chest radiographs, and laboratory parameters were obtained retrospectively from hospital records. The outcome was noted in terms of course, patients discharged, still admitted (at the time of the study), or death.

Results: Out of 231 cases, most were males (78.3%) with a mean age of 39.8 years. Comorbidities were present in 21.2% of patients, diabetes mellitus and hypertension being the most common. The most common symptoms were dry cough (81, 35%), fever (64, 27.7%), sore throat (36, 15.6%); asymptomatic infection noted in 108 (46.8%) patients. The presence of comorbidities was an independent predictor of symptomatic disease (OR-2.66; 95%CI 1.08-6.53, = 0·03). None of the patients progressed to moderate-severe COVID-19, and there were no deaths.

Conclusions: A large proportion of patients remained asymptomatic whereas those with comorbidities were more likely to be symptomatic. Most with mild disease had a stable disease course, barring few complication in those with comorbidities. The pandemic continues to grow as large number of asymptomatic cases may go undiagnosed.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1198_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928080PMC
December 2020

A Masquerader of Neonatal Persistent Pulmonary Hypertension.

J Pediatr 2021 06 3;233:281-282. Epub 2021 Mar 3.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1016/j.jpeds.2021.02.068DOI Listing
June 2021

Silencing of an Ubiquitin Ligase Increases Grain Width and Weight in Rice.

Front Genet 2020 12;11:600378. Epub 2021 Jan 12.

National Institute of Plant Genome Research, New Delhi, India.

Many quantitative trait loci (QTLs) have been identified by molecular genetic studies which control grain size by regulating grain width, length, and/or thickness. () is one such QTL that codes for a RING-type E3 ubiquitin ligase and increases grain size by regulating grain width through ubiquitin-mediated degradation of unknown substrates. A natural variation (single-nucleotide polymorphism at the 346 position) in the functional domain-coding region of in rice genotypes has been shown to cause an increase in grain width/weight in rice. However, this variation is absent in rice genotypes. In this study, we report that reduced expression of can alter grain size, even though natural sequence variation is not responsible for increased grain size in rice genotypes. shows high expression in seed development stages and the protein localizes to the nucleus and cytoplasm. Downregulation of by RNAi technology results in wider and heavier grains. Microscopic observation of grain morphology suggests that OsGW2 determines grain size by influencing both cell expansion and cell proliferation in spikelet hull. Using transcriptome analysis, upregulated genes related to grain size regulation have been identified among 1,426 differentially expressed genes in an _RNAi transgenic line. These results reveal that is a negative regulator of grain size in rice and affects both cell number and cell size in spikelet hull.
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http://dx.doi.org/10.3389/fgene.2020.600378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835794PMC
January 2021

Linking void and interphase evolution to electrochemistry in solid-state batteries using operando X-ray tomography.

Nat Mater 2021 Apr 28;20(4):503-510. Epub 2021 Jan 28.

School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

Despite progress in solid-state battery engineering, our understanding of the chemo-mechanical phenomena that govern electrochemical behaviour and stability at solid-solid interfaces remains limited compared to at solid-liquid interfaces. Here, we use operando synchrotron X-ray computed microtomography to investigate the evolution of lithium/solid-state electrolyte interfaces during battery cycling, revealing how the complex interplay among void formation, interphase growth and volumetric changes determines cell behaviour. Void formation during lithium stripping is directly visualized in symmetric cells, and the loss of contact that drives current constriction at the interface between lithium and the solid-state electrolyte (LiSnPS) is quantified and found to be the primary cause of cell failure. The interphase is found to be redox-active upon charge, and global volume changes occur owing to partial molar volume mismatches at either electrode. These results provide insight into how chemo-mechanical phenomena can affect cell performance, thus facilitating the development of solid-state batteries.
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http://dx.doi.org/10.1038/s41563-020-00903-2DOI Listing
April 2021

Malignant Degeneration of Biopsy-Proven Hamartoma to Chondrosarcoma.

Cureus 2020 Dec 18;12(12):e12150. Epub 2020 Dec 18.

Surgery, Creighton University School of Medicine, Omaha, USA.

Pulmonary hamartomas are benign lesions that are often managed conservatively in the absence of respiratory symptoms. Increasing reports of malignant transformation question if a more aggressive treatment or surveillance practice for these lesions is warranted in adult patients. Herein, we describe a case of a 67-year-old man with a long history of pulmonary hamartoma that demonstrated malignant degeneration into spindle cell malignancy with chondromatous differentiation. This case illustrates the aggressive nature of sarcomatous disease arising from hamartomas and, with a handful of other cases in the literature, points to the question of whether pulmonary hamartomas arising in late adulthood should follow a more intensive treatment or surveillance algorithm given increased concern for malignant potential.
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http://dx.doi.org/10.7759/cureus.12150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814419PMC
December 2020

'Lip-to-Tip' study: comparison of three methods to determine optimal insertion length of endotracheal tube in neonates.

Eur J Pediatr 2021 May 3;180(5):1459-1466. Epub 2021 Jan 3.

Division of Neonatology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

The aim of this prospective observational study was to compare the incidence of endotracheal tube (ETT) malposition using weight-based (Tochen), gestation-based (Kempley), and nasotragal length (NTL) methods in deceased neonates and fresh stillbirths. We enrolled deceased neonates and fresh stillbirths within 2 ± 1 h of death or delivery, respectively; without hydrops, tracheostomy or major congenital anomalies affecting face, neck, or thorax. Each enrolled subject was intubated orotracheally, with lip-to-tip distance determined by three methods in random succession. Chest X-ray was acquired after each insertion. The primary outcome was proportion of malpositioned ETTs on chest X-ray (defined as ETT tip not lying between upper border of T1 and lower border of T2 vertebrae), assessed by two experts masked to the methods used. The proportion of malpositioned tubes was not significantly different with any of the three methods: (weight 27/50 (54%), gestation 35/50 (70%), and NTL 35/50 (70%), p value 0.055). The malpositioned tubes were too far in (87/150; 58%) than too far out (10/150; 6.7%).Conclusions: None of the currently recommended methods accurately predicts optimal ETT length in neonates. There is an urgent need for newer bedside modalities for estimating ETT position in neonates. What is known? • NRP guidelines recommend gestation-based and nasotragal length (NTL) methods to estimate initial ETT depth in neonates. Weight-based (Tochen) method is still widely used in neonatal units for ETT depth estimation. Evidence till date has not proven superiority of one method over the other. What is new? • All three methods for ETT depth estimation (Tochen, gestation-based, and NTL) resulted in high rates of ETT malposition in neonates. Formulae, devised from this study based on linear regression models, did not perform well for estimation of optimal ETT position.
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http://dx.doi.org/10.1007/s00431-020-03919-7DOI Listing
May 2021

VDAC1 in the diseased myocardium and the effect of VDAC1-interacting compound on atrial fibrosis induced by hyperaldosteronism.

Sci Rep 2020 12 16;10(1):22101. Epub 2020 Dec 16.

Cardiac Arrhythmia Research Laboratory, Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, 84105, Beer Sheva, Israel.

The voltage-dependent anion channel 1 (VDAC1) is a key player in mitochondrial function. VDAC1 serves as a gatekeeper mediating the fluxes of ions, nucleotides, and other metabolites across the outer mitochondrial membrane, as well as the release of apoptogenic proteins initiating apoptotic cell death. VBIT-4, a VDAC1 oligomerization inhibitor, was recently shown to prevent mitochondrial dysfunction and apoptosis, as validated in mouse models of lupus and type-2 diabetes. In the present study, we explored the expression of VDAC1 in the diseased myocardium of humans and rats. In addition, we evaluated the effect of VBIT-4 treatment on the atrial structural and electrical remodeling of rats exposed to excessive aldosterone levels. Immunohistochemical analysis of commercially available human cardiac tissues revealed marked overexpression of VDAC1 in post-myocardial infarction patients, as well as in patients with chronic ventricular dilatation\dysfunction. In agreement, rats exposed to myocardial infarction or to excessive aldosterone had a marked increase of VDAC1 in both ventricular and atrial tissues. Immunofluorescence staining indicated a punctuated appearance typical for mitochondrial-localized VDAC1. Finally, VBIT-4 treatment attenuated the atrial fibrotic load of rats exposed to excessive aldosterone without a notable effect on the susceptibility to atrial fibrillation episodes induced by burst pacing. Our results indicate that VDAC1 overexpression is associated with myocardial abnormalities in common pathological settings. Our data also indicate that inhibition of the VDAC1 can reduce excessive fibrosis in the atrial myocardium, a finding which may have important therapeutic implications. The exact mechanism\s of this beneficial effect need further studies.
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http://dx.doi.org/10.1038/s41598-020-79056-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744539PMC
December 2020

Mitochondria and nucleus cross-talk: Signaling in metabolism, apoptosis, and differentiation, and function in cancer.

IUBMB Life 2021 03 12;73(3):492-510. Epub 2020 Nov 12.

Department of Life Sciences, Ben-Gurion University of the Negev and the National Institute for Biotechnology in the Negev, Beersheba, Israel.

The cross-talk between the mitochondrion and the nucleus regulates cellular functions, including differentiation and adaptation to stress. Mitochondria supply metabolites for epigenetic modifications and other nuclear-associated activities and certain mitochondrial proteins were found in the nucleus. The voltage-dependent anion channel 1 (VDAC1), localized at the outer mitochondrial membrane (OMM) is a central protein in controlling energy production, cell growth, Ca homeostasis, and apoptosis. To alter the cross-talk between the mitochondria and the nucleus, we used specific siRNA to silence the expression of VDAC1 in glioblastoma (GBM) U87-MG and U118-MG cell-derived tumors, and then monitored the nuclear localization of mitochondrial proteins and the methylation and acetylation of histones. Depletion of VDAC1 from tumor cells reduced metabolism, leading to inhibition of tumor growth, and several tumor-associated processes and signaling pathways linked to cancer development. In addition, we demonstrate that certain mitochondrial pro-apoptotic proteins such as caspases 3, 8, and 9, and p53 were unexpectedly overexpressed in tumors, suggesting that they possess additional non-apoptotic functions. VDAC1 depletion and metabolic reprograming altered their expression levels and subcellular localization, specifically their translocation to the nucleus. In addition, VDAC1 depletion also leads to epigenetic modifications of histone acetylation and methylation, suggesting that the interchange between metabolism and cancer signaling pathways involves mitochondria-nucleus cross-talk. The mechanisms regulating mitochondrial protein trafficking into and out of the nucleus and the role these proteins play in the nucleus remain to be elucidated.
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http://dx.doi.org/10.1002/iub.2407DOI Listing
March 2021

VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases.

Biomolecules 2020 10 26;10(11). Epub 2020 Oct 26.

Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.

The voltage-dependent anion channel 1 (VDAC1) protein, is an important regulator of mitochondrial function, and serves as a mitochondrial gatekeeper, with responsibility for cellular fate. In addition to control over energy sources and metabolism, the protein also regulates epigenomic elements and apoptosis via mediating the release of apoptotic proteins from the mitochondria. Apoptotic and pathological conditions, as well as certain viruses, induce cell death by inducing VDAC1 overexpression leading to oligomerization, and the formation of a large channel within the VDAC1 homo-oligomer. This then permits the release of pro-apoptotic proteins from the mitochondria and subsequent apoptosis. Mitochondrial DNA can also be released through this channel, which triggers type-Ι interferon responses. VDAC1 also participates in endoplasmic reticulum (ER)-mitochondria cross-talk, and in the regulation of autophagy, and inflammation. Its location in the outer mitochondrial membrane, makes VDAC1 ideally placed to interact with over 100 proteins, and to orchestrate the interaction of mitochondrial and cellular activities through a number of signaling pathways. Here, we provide insights into the multiple functions of VDAC1 and describe its involvement in several diseases, which demonstrate the potential of this protein as a druggable target in a wide variety of pathologies, including cancer.
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http://dx.doi.org/10.3390/biom10111485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693975PMC
October 2020

Partial anomalous pulmonary venous return in a patient undergoing left upper lobectomy for adenocarcinoma of the lung: A case report.

Int J Surg Case Rep 2020 25;76:90-93. Epub 2020 Sep 25.

Creighton University, Department of Surgery, 7710 Mercy Rd., Suite 501, Omaha, NE, 68124, United States. Electronic address:

Introduction: Partial anomalous pulmonary venous return (PAPVR) is a rare congenital heart disease that complicates surgical management of pulmonary pathology.

Case Presentation: This case describes the successful management of a 73-year-old female with a left upper lobe adenocarcinoma and pre-operative discovery of left superior anomalous pulmonary venous return into the innominate vein. This patient presented to our clinic for evaluation regarding her newly discovered adenocarcinoma of the lung. Here, we also discuss findings in the literature for management of these patients regarding the importance of preoperative evaluation to determine the extent to which a lobectomy will alter pulmonary function with special emphasis on identifying patients at risk of increased shunting leading to cardiopulmonary failure.

Conclusion: Consideration should focus on the extent of the shunting, the presence of symptoms, and underlying right heart strain or pulmonary hypertension.
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http://dx.doi.org/10.1016/j.ijscr.2020.09.153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533348PMC
September 2020

Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance.

Clin Epigenetics 2020 09 14;12(1):139. Epub 2020 Sep 14.

Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Università degli Studi della Campania "Luigi Vanvitelli", Caserta, Italy.

Background: PADI6 is a component of the subcortical maternal complex, a group of proteins that is abundantly expressed in the oocyte cytoplasm, but is required for the correct development of early embryo. Maternal-effect variants of the subcortical maternal complex proteins are associated with heterogeneous diseases, including female infertility, hydatidiform mole, and imprinting disorders with multi-locus imprinting disturbance. While the involvement of PADI6 in infertility is well demonstrated, its role in imprinting disorders is less well established.

Results: We have identified by whole-exome sequencing analysis four cases of Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance whose mothers are carriers of PADI6 variants. In silico analysis indicates that these variants result in loss of function, and segregation analysis suggests they act as either recessive or dominant-negative maternal-effect mutations. Genome-wide methylation analysis revealed heterogeneous and extensively altered methylation profiles of imprinted loci in the patients, including two affected sisters, but not in their healthy siblings.

Conclusion: Our results firmly establish the role of PADI6 in imprinting disorders. We report loss-of-function maternal-effect variants of PADI6 that are associated with heterogeneous multi-locus imprinting disturbances in the progeny. The rare finding of two siblings affected by Beckwith-Wiedemann syndrome suggests that in some cases, familial recurrence risk of these variants may be high. However, the heterogeneous phenotypes of the other pedigrees suggest that altered oocyte PADI6 function results in stochastic maintenance of methylation imprinting with unpredictable consequences on early embryo health.
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http://dx.doi.org/10.1186/s13148-020-00925-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489023PMC
September 2020

Successful Treatment of Collodion Baby with Acitretin: A Report of Two Cases.

Indian J Pediatr 2021 01 18;88(1):95-96. Epub 2020 Aug 18.

Department of Dermatology, All India Institute of Medical Sciences, New Delhi, India.

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http://dx.doi.org/10.1007/s12098-020-03474-xDOI Listing
January 2021

Identification of functional epitopes of structural proteins and in-silico designing of dual acting multiepitope anti-tick vaccine against emerging Crimean-Congo hemorrhagic fever virus.

Eur J Pharm Sci 2020 Aug 30;151:105396. Epub 2020 May 30.

Division of Virology, Defence Research and Development Establishment, Jhansi Road, Gwalior, PIN-474002, India. Electronic address:

Recurrent outbreaks of Crimean-Congo hemorrhagic fever (CCHF) virus infection in different parts of world are a major global health concern. The CCHF viral infection is associated with severe hemorrhagic fevers and mortality up to 40%. More than 30 countries in Asia, Europe and Africa are affected with CCHF infection. Prevention of infection through vaccine becomes more important when no effective antiviral and associated therapies are available. Further ticks play a crucial role in maintenance and transmission of CCHFV. Therefore, the control of transmission by ticks is warranted for ultimate prevention of outbreak. The study employed a series of immunoinformatics approaches to design novel multiepitope vaccine targeting highly immunodominant epitopes of major structural proteins (Nucleoprotein and Glycoprotein complex) of CCHFV. Vaccine was designed by incorporating linear and conformational B cell, helper and cytotoxic T cell epitopes from these crucial immunogenic proteins adjoined with appropriate linkers and adjuvant. This vaccine construct was also complemented with a highly immunogenic and conserved protective tick salivary antigen named subolesin to impart dual activity as a unique transmission blocking vaccine. The B-cell peptides were also experimentally validated. The designed vaccine was further in silico validated for its physiochemical properties, allergenicity and immunogenicity etc. The proposed candidate vaccine construct has the potential to function both as a vaccine against CCHF virus as well as a universal anti-tick vaccine.
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http://dx.doi.org/10.1016/j.ejps.2020.105396DOI Listing
August 2020

Surface diffusion manifestation in electrodeposition of metal anodes.

Phys Chem Chem Phys 2020 May 8;22(20):11286-11295. Epub 2020 May 8.

School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA.

Metal anode-based battery systems have been deemed indispensable towards energy storage renaissance engendering extensive research into strategies countering dendritic growth of metal electrodeposition. Fundamentally, the morphological evolution of a material is uniquely characterized by the heights of its self-diffusion barrier across multiple pathways. Herein, based on a coarse-grained kinetic Monte Carlo method, we derive insights into the nucleation and growth of metallic electrodeposits in liquid electrolytes, governed by surface self-diffusion characteristics cognizant of the diverse diffusion routes including terrace, away from step and interlayer pathways. We deconvolve the roles played by each of these surface diffusion mechanisms in conjunction with the electrochemical reaction rate on the deposition morphology regime (film vs. mossy vs. fractal). We identify interlayer diffusion as the predominant morphology-determining mechanism; dendrite-free deposition even at moderate current rates constrains this diffusion barrier to an upper limit. Additionally, we highlight subtle features amidst the realm of the morphological growth assortment that connect to the cell's electrochemical performance. Finally, we delineate morphological features of Li, Na, Mg and Al based on their respective surface diffusion barriers and applied overpotentials, and provide a baseline for the interpretation of experimental observations. This fundamental study sheds light on the mesoscale underpinnings of morphological variances in mono-valent and multi-valent metal electrodeposition.
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http://dx.doi.org/10.1039/d0cp01352hDOI Listing
May 2020

Double-Edged Effect of Temperature on Lithium Dendrites.

ACS Appl Mater Interfaces 2020 May 12;12(21):23931-23938. Epub 2020 May 12.

School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.

Lithium metal, although attracting renewed interest for the next revolution in energy storage, continues to be challenged with the detrimental dendrite formation. Recent experimental reports have demonstrated the contrasting impact of thermal attributes on the electrodeposition morphology, showcasing the alleviation and/or aggravation of dendrite formation. Herein, we present a comprehensive discourse to discern the thermally activated physical mechanisms governing lithium electrodeposition morphology. We report that the synergistic effect of enhanced electrolyte transport and surface self-diffusion under a uniform thermal field (∼75 °C) enables adequate dendrite suppression, even at high reaction rates. However, in contrast to this, a localization of the thermal field substantially increases the exchange current density of the confined region, instigating the growth of needle dendrites. Based on our mesoscale analysis, we demarcate safety limits for such an event, beyond which dendrite growth is inevitably triggered. Therefore, though the operational strategy of elevating the cell temperature promises to resolve the challenge of stable electrodeposition, it comes along with the caveat. This fundamental study provides a detailed insight into underlying electrochemical-thermal complexations, critical to the performance and safety of metal-based rechargeable batteries.
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http://dx.doi.org/10.1021/acsami.0c04355DOI Listing
May 2020

Decreasing the Ion Diffusion Pathways for the Intercalation of Multivalent Cations into One-Dimensional TiS Nanobelt Arrays.

ACS Appl Mater Interfaces 2020 May 9;12(19):21788-21798. Epub 2020 Apr 9.

Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, United States.

The sparse selection of available cathode materials that allow for reversible intercalation (deintercalation) of Al species represents a major hurdle in the development of efficient Al-ion batteries. Herein, we developed cathodes based on TiS nanobelts that are capable of withstanding the high charge density of Al-ion species with minimal host lattice/ion interactions. The fabricated TiS nanobelts are highly anisotropic and are directly grown on a carbon current collector yielding a spatially controlled array. The sum of evidence presented in this work indicates that one-dimensional TiS nanobelt arrays can reversibly accommodate an unprecedented amount of Al ion species within their layered structure with no significant volume expansion as well as full retention of the nanobelt morphology. Thus, the one-dimensional morphology, nanoscale dimensions, short ion diffusion paths, high electrical conductivity, and absence of additives that hinder ion migration lead to Al-based TiS electrochemical devices exhibiting high specific capacity, less capacity fade, and resilience under higher cycling rates at both room temperature and elevated temperatures when compared to TiS platelets. We also present the effects of sulfur vacancies on the electrochemical performance of Al-based TiS nanobelt array batteries. Although Al-ion batteries are still in their infancy, we believe our TiS nanobelt array cathode insertion hosts may play an important role in addressing the poor kinetics of solid-state Al-ion diffusion to enable efficient alternatives beyond lithium energy storage devices.
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http://dx.doi.org/10.1021/acsami.9b21702DOI Listing
May 2020

Outcome of extremely low birth weight (ELBW) infants from a birth cohort (2013-2018) in a tertiary care unit in North India.

J Perinatol 2020 05 14;40(5):743-749. Epub 2020 Feb 14.

Division of Neonatology, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Objective: To evaluate mortality and short-term morbidities in extremely low birth weight (ELBW) infants (<1000 g) in a birth cohort in North India.

Methods: In-hospital data of 231 ELBW infants (Jan 2013 to Sept 2018) were collected from a prospectively maintained electronic database by using standard definitions.

Results: The mean (SD) gestation and birth weight were 27.9 (2.2) weeks and 783 (133) g, respectively. Major morbidities included respiratory distress syndrome (n = 132, 57%), moderate-to-severe bronchopulmonary dysplasia (n = 62, 26.8%), hemodynamically significant patent ductus arteriosus (n = 65, 28%), intracranial hemorrhage ≥ grade II (n = 38, 16%), and culture-positive sepsis (n = 44, 19%). Median (IQR) duration of hospital stay (survivors) was 50 (17-79) days. The overall survival was 62%. On logistic regression, severe birth asphyxia, gestation ≤26 weeks, and respiratory distress syndrome were major predictors of mortality.

Conclusion: In the current ELBW cohort, nearly two-thirds survived until discharge, who had considerable morbidities needing prolonged hospital stay. This study can be utilized for counseling and planning of care of ELBW infants in similar settings.
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http://dx.doi.org/10.1038/s41372-020-0604-6DOI Listing
May 2020

Non-immune Hydrops in Neonates: A Tertiary Care Center Experience.

Indian Pediatr 2020 04 5;57(4):321-323. Epub 2020 Feb 5.

Division of Neonatology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Objective: To evaluate the clinical profile and outcome of neonates with non-immune hydrops (NIH).

Methods: Data of all the NIH cases admitted to neonatal intensive care unit at our center, New Delhi from January, 2010 to October, 2017 were extracted from hospital records, which included clinical profile and outcomes.

Results: Of the 17,299 total births, 27 neonates were identified to have NIH. Antenatal interventions were undertaken in five (18.5%) cases. The most common etiology of NIH was cardiac (n=5; 18.5%). Two babies with chylothorax were successfully managed with octreotide infusions. Overall survival rate of NIH was 70.3% (n=19). All neonates with a suspected genetic syndrome died.

Conclusions: Multidisciplinary team including obstetricians, pediatric surgeons, geneticists and neonatologists can improve outcome in neonates with NIH.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223915PMC
April 2020

Metal-free visible-light-mediated organophotoredox catalysis: synthesis of 3-functionalized indole via C-C, C-N bond formation.

Mol Divers 2021 May 3;25(2):1103-1109. Epub 2020 Feb 3.

Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad, 211002, India.

A visible-light-mediated, mild and one-pot three-component reaction in the presence of organophotoredox catalyst Eosin Y using EtOH:HO as reaction medium for the synthesis of 3-functionalized indole derivatives was developed. Visible light used in the protocol is green, inexpensive, readily available energy source. The sustainable reagents make the protocol compatible with green chemistry demands.
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http://dx.doi.org/10.1007/s11030-020-10044-yDOI Listing
May 2021
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