JYOTI TANWAR - Academia.edu (original) (raw)

Papers by JYOTI TANWAR

Cells, 2022

Inter-organellar communication is emerging as one of the most crucial regulators of cellular phys... more Inter-organellar communication is emerging as one of the most crucial regulators of cellular physiology. One of the key regulators of inter-organellar communication is Mitofusin-2 (MFN2). MFN2 is also involved in mediating mitochondrial fusion–fission dynamics. Further, it facilitates mitochondrial crosstalk with the endoplasmic reticulum, lysosomes and melanosomes, which are lysosome-related organelles specialized in melanin synthesis within melanocytes. However, the role of MFN2 in regulating melanocyte-specific cellular function, i.e., melanogenesis, remains poorly understood. Here, using a B16 mouse melanoma cell line and primary human melanocytes, we report that MFN2 negatively regulates melanogenesis. Both the transient and stable knockdown of MFN2 leads to enhanced melanogenesis, which is associated with an increase in the number of mature (stage III and IV) melanosomes and the augmented expression of key melanogenic enzymes. Further, the ectopic expression of MFN2 in MFN2-si...

The compounding problem of microbial resistance has become a global threat nowadays and demands u... more The compounding problem of microbial resistance has become a global threat nowadays and demands urgent attention. Given the limited number of clinically proven drugs available, reversion towards compounds from natural resources have become renewed source of interest. Utilization of novel and potent antimicrobial agents with different targets can act as accessories to antibiotic therapy. Considerable amount of research has been conducted on the various advantages of secondary metabolites produced by different plants. Among these, polyphenols have come into sight over the past few decades as a potential source to promote human health. This article summarizes the various health benefits of EGCG, the major component of green tea polyphenols with more emphasis on the anti-microbial properties of EGCG.

Asset Liability Management has gained popularity in the banking sector. Earlier banks focused on ... more Asset Liability Management has gained popularity in the banking sector. Earlier banks focused on asset allocation, but now the management of assets and liabilities is equally essential. Asset liability management targets the optimum distribution of funds in assets and managing liabilities so that banks can earn higher profits and minimize risk. In this paper, the optimization of assets and liabilities of Indian banks has been concentrated using mathematical models. Combining the Analytical Hierarchy Process (AHP) and Goal Programming (GP) model has been used to solve the optimization problem. AHP is a multi-criteria decision-making approach for deriving priority weights. Goal Programming is a linear programming model to solve complex issues having multiple objectives. In this paper, the primary data gathered from Bank senior managers have been analyzed using the AHP approach to derive weights for criteria. These weights are assigned to goals in goal programming to prioritize the goa...

The EMBO Journal, 2021

Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here,... more Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2gib005Δ8/+) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta‐b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2‐mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVE...

The aim of this study was to evaluate the antifungal potential of Resorcinol (Res) against human ... more The aim of this study was to evaluate the antifungal potential of Resorcinol (Res) against human fungal pathogen, Candida albicans. In this study, we explored that Res displayed its antifungal potential against two reference strains of C. albicans (ATCC 10261 and ATCC 24433) and five clinical isolates tested. We also showed that Res is equally effective against various non- albicans species of Candida as well thereby demonstrating its wide repertoire. Notably, the antifungal effect of Res seems to be independent of the activity of major drug efflux pumps transporter which is the major cause of drug resistance in C. albicans. Finally, we also demonstrated that Res inhibits the serum and nitrogen starvation dependent yeast to hyphal transition in C. albicans which is one of the major virulence attribute. Taken together, Res exhibited promising in vitro antifungal properties and potent inhibitor of yeast to hyphal transition that could be used for the treatment of Candida infections. F...

In earlier years, there was abundance of funds in banks in the form of demand and savings deposit... more In earlier years, there was abundance of funds in banks in the form of demand and savings deposits. Hence, the focus of banks was mainly on asset management. But intense competition and volatility of interest rate due to banking reforms reduced the availability of low-cost funds and therefore, banks focused on liability management as well. These pressures call for structured and comprehensive measures and not just ad hoc action. This is how banks started to concentrate more on the management of both sides of the balance sheet. As a result, the concept of asset-liability management originated in India and introduced in the Indian banking industry since 1st April 1999 to administer the risk management aspects. This paper attempts to optimize assets and liabilities of banks using goal programming technique. Secondary data is collected from annual reports of Allahabad bank from 2010-2019 and RBI website is used for modelling. The findings show that in Allahabad bank, goal programming he...

Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate ... more Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate of less than 10%. Most of the PC associated deaths are due to metastasis to secondary sites. Calcium (Ca2+) signaling plays a critical role in regulating hallmarks of cancer progression including cell proliferation, migration and apoptotic resistance. Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous pathway responsible for Ca2+ influx into non-excitable cells. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in 6 PC cell lines and found that Orai3 forms a functional SOCE in PC cells. Our in vitro functional assays show that Orai3 regula...

Molecular Aspects of Medicine

Viral infections are one of the leading causes of human illness. Viruses take over host cell sign... more Viral infections are one of the leading causes of human illness. Viruses take over host cell signaling cascades for their replication and infection. Calcium (Ca2+) is a versatile and ubiquitous second messenger that modulates plethora of cellular functions. In last two decades, a critical role of host cell Ca2+ signaling in modulating viral infections has emerged. Furthermore, recent literature clearly implicates a vital role for the organellar Ca2+ dynamics (influx and efflux across organelles) in regulating virus entry, replication and severity of the infection. Therefore, it is not surprising that a number of viral infections including current SARS-CoV-2 driven COVID-19 pandemic are associated with dysregulated Ca2+ homeostasis. The focus of this review is to first discuss the role of host cell Ca2+ signaling in viral entry, replication and egress. We further deliberate on emerging literature demonstrating hijacking of the host cell Ca2+ dynamics by viruses. In particular, a variety of viruses including SARS-CoV-2 modulate lysosomal and cytosolic Ca2+ signaling for host cell entry and replication. Moreover, we delve into the recent studies, which have demonstrated the potential of several FDA-approved drugs targeting Ca2+ handling machinery in inhibiting viral infections. Importantly, we discuss the prospective of targeting intracellular Ca2+ signaling for better management and treatment of viral pathogenesis including COVID-19. Finally, we highlight the key outstanding questions in the field that demand critical and timely attention.

Indian Journal of Finance and Banking

This study examines the efficiency of the overall Indian banking industry using Data Envelopment ... more This study examines the efficiency of the overall Indian banking industry using Data Envelopment Analysis (DEA) and to perform a comparative efficiency analysis of public, private, and foreign banks using six varied forms. Also, providing ranks to the banks based on their efficiency. The study incorporates BCC output-oriented DEA model using a sample of 50 Indian banks (public banks = 17, private banks = 18, foreign banks = 15) for a period ranging from 2009-10 to 2018-19, hence incorporating the after-effects of the financial crisis and demonetization, this study uses panel data from 2009-10 to 2018-19. The results showed that most of the Indian banks fall on the efficient side or are near to full efficiency. However, public banks outperform private and foreign banks in terms of their average efficiency. Results also specify that the performance of banks is sensitive to input-output variables, units under evaluation, and choice of the model. The current study has just focused on th...

Cell Calcium

Ion channels in particular Calcium (Ca2+) channels play a critical role in physiology by regulati... more Ion channels in particular Calcium (Ca2+) channels play a critical role in physiology by regulating plethora of cellular processes ranging from cell proliferation, differentiation, transcriptional regulation and programmed cell death. One such physiologically important and highly Ca2+ selective channel family is Orai channels consisting of three homologs Orai1, Orai2 and Orai3. Orai channels are responsible for Ca2+ influx across the plasma membrane in response to decrease in Endoplasmic Reticulum (ER) Ca2+ stores. STIM1/STIM2 proteins sense the reduction in ER Ca2+ levels and activate Orai channels for restoring ER Ca2+ as well as for driving cellular functions. This signaling cascade is known as Store Operated Ca2+ Entry (SOCE). Although Orai1 is the ubiquitous SOCE channel protein, Orai2 and Orai3 mediate SOCE in certain specific tissues. Further, mammalian specific homolog Orai3 forms heteromultimeric channel with Orai1 for constituting Arachidonic acid regulated Ca2+ (ARC) channels or arachidonic acid metabolite Leukotriene C4 (LTC4) regulated Ca2+ (LRC) channels. Literature suggests that Orai3 regulates Breast, Prostate, Lung and Gastrointestinal cancers by either forming Store Operated Ca2+ (SOC) or ARC/LRC channels in the cancerous cells but not in healthy tissue. In this review, we would discuss the role of Orai3 in these cancers and would highlight the potential of therapeutic targeting of Orai3 for better management and treatment of cancer. Finally, we will deliberate on key outstanding questions in the field that demand critical attention and further studies.

Development

In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical f... more In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical for both development and regeneration. While the fate-commitment events have distinct transcriptional footprints, fate-biasing is often transitory and metastable, and is thought to be moulded by epigenetic programs. Hence molecular basis of specification is difficult to define. In this study, we establish a role of a histone variant H2a.z.2 in specification of melanocyte lineage from multipotent neural crest cells. Silencing of H2a.z.2 reduces the number of melanocyte precursors in developing zebrafish embryos, and from mouse embryonic stem cells in vitro. We demonstrate that this histone variant occupies nucleosomes in the promoter of key melanocyte determinant Mitf, and enhances its induction. CRISPR-Cas9 based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby our study establishes the role of a histone variant u...

Cell Calcium

Store Operated Ca2+ Entry (SOCE) mediated by Orai channels is a ubiquitous Ca2+ influx pathway th... more Store Operated Ca2+ Entry (SOCE) mediated by Orai channels is a ubiquitous Ca2+ influx pathway that regulates several cellular functions. We have earlier reported that Orai3, the mammalian specific Orai1 homolog, plays a critical role in breast cancer progression. More recently, Orai3 was demonstrated to regulate prostate and lung tumorigenesis. Although the tumorigenic potential of Orai3 is associated with increase in its expression, the molecular machinery regulating its expression remains largely unexplored. Here, by performing extensive bioinformatics analysis and functional studies, we identify and characterize micro-RNAs (miRNAs) that regulate Orai3 expression and function. We demonstrate that miR18a and miR18b positively regulate Orai3 whereas miR34a represses Orai3 expression and function. All these miRs exert their effect on Orai3 by virtue of their direct action on Orai3 3'UTR. These miRs provide novel opportunities for targeting Orai3 for better management of cancer. This study further opens up the possibility of targeting specific Orai homologs by different miRs in tissue and disease specific context.

In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical f... more In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical for both development and regeneration. While the fate-commitment events have distinct transcriptional footprints, fate-biasing is often transitory and metastable, and is thought to be moulded by epigenetic programs. Hence molecular basis of specification is difficult to define. In this study, we establish a role of a histone variant H2a.z.2 in specification of melanocyte lineage from multipotent neural crest cells. Silencing of H2a.z.2 reduces the number of melanocyte precursors in developing zebrafish embryos, and from mouse embryonic stem cells in vitro. We demonstrate that this histone variant occupies nucleosomes in the promoter of key melanocyte determinant Mitf, and enhances its induction. CRISPR-Cas9 based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby our study establishes a histone based specification c...

Cell calcium, 2018

Calcium (Ca) signaling plays a critical role in regulating plethora of cellular functions includi... more Calcium (Ca) signaling plays a critical role in regulating plethora of cellular functions including cell survival, proliferation and migration. The perturbations in cellular Ca homeostasis can lead to cell death either by activating autophagic pathways or through induction of apoptosis. Endoplasmic reticulum (ER) is the major storehouse of Ca within cells and a number of physiological agonists mediate ER Ca release by activating IP receptors (IPR). This decrease in ER Ca levels is sensed by STIM, which physically interacts and activates plasma membrane Ca selective Orai channels. Emerging literature implicates a key role for STIM1, STIM2, Orai1 and Orai3 in regulating both cell survival and death pathways. In this review, we will retrospect the work highlighting the role of STIM and Orai homologs in regulating cell death signaling. We will further discuss the rationales that could explain the dual role of STIM and Orai proteins in regulating cell fate decisions.

Copyright © 2014 Jyoti Tanwar et al. This is an open access article distributed under the Creativ... more Copyright © 2014 Jyoti Tanwar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The resistance among various microbial species (infectious agents) to different antimicrobial drugs has emerged as a cause of public health threat all over the world at a terrifying rate. Due to the pacing advent of new resistancemechanisms and decrease in efficiency of treating common infectious diseases, it results in failure ofmicrobial response to standard treatment, leading to prolonged illness, higher expenditures for health care, and an immense risk of death. Almost all the capable infecting agents (e.g., bacteria, fungi, virus, and parasite) have employed high levels of multidrug resistance (MDR) with enhanced morbidity and mortality; thus, they are referred to as “super bugs. ” Although the development of MDR is a natural phen...

Cells, 2022

Inter-organellar communication is emerging as one of the most crucial regulators of cellular phys... more Inter-organellar communication is emerging as one of the most crucial regulators of cellular physiology. One of the key regulators of inter-organellar communication is Mitofusin-2 (MFN2). MFN2 is also involved in mediating mitochondrial fusion–fission dynamics. Further, it facilitates mitochondrial crosstalk with the endoplasmic reticulum, lysosomes and melanosomes, which are lysosome-related organelles specialized in melanin synthesis within melanocytes. However, the role of MFN2 in regulating melanocyte-specific cellular function, i.e., melanogenesis, remains poorly understood. Here, using a B16 mouse melanoma cell line and primary human melanocytes, we report that MFN2 negatively regulates melanogenesis. Both the transient and stable knockdown of MFN2 leads to enhanced melanogenesis, which is associated with an increase in the number of mature (stage III and IV) melanosomes and the augmented expression of key melanogenic enzymes. Further, the ectopic expression of MFN2 in MFN2-si...

The compounding problem of microbial resistance has become a global threat nowadays and demands u... more The compounding problem of microbial resistance has become a global threat nowadays and demands urgent attention. Given the limited number of clinically proven drugs available, reversion towards compounds from natural resources have become renewed source of interest. Utilization of novel and potent antimicrobial agents with different targets can act as accessories to antibiotic therapy. Considerable amount of research has been conducted on the various advantages of secondary metabolites produced by different plants. Among these, polyphenols have come into sight over the past few decades as a potential source to promote human health. This article summarizes the various health benefits of EGCG, the major component of green tea polyphenols with more emphasis on the anti-microbial properties of EGCG.

Asset Liability Management has gained popularity in the banking sector. Earlier banks focused on ... more Asset Liability Management has gained popularity in the banking sector. Earlier banks focused on asset allocation, but now the management of assets and liabilities is equally essential. Asset liability management targets the optimum distribution of funds in assets and managing liabilities so that banks can earn higher profits and minimize risk. In this paper, the optimization of assets and liabilities of Indian banks has been concentrated using mathematical models. Combining the Analytical Hierarchy Process (AHP) and Goal Programming (GP) model has been used to solve the optimization problem. AHP is a multi-criteria decision-making approach for deriving priority weights. Goal Programming is a linear programming model to solve complex issues having multiple objectives. In this paper, the primary data gathered from Bank senior managers have been analyzed using the AHP approach to derive weights for criteria. These weights are assigned to goals in goal programming to prioritize the goa...

The EMBO Journal, 2021

Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here,... more Long non‐coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial‐associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2gib005Δ8/+) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta‐b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2‐mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVE...

The aim of this study was to evaluate the antifungal potential of Resorcinol (Res) against human ... more The aim of this study was to evaluate the antifungal potential of Resorcinol (Res) against human fungal pathogen, Candida albicans. In this study, we explored that Res displayed its antifungal potential against two reference strains of C. albicans (ATCC 10261 and ATCC 24433) and five clinical isolates tested. We also showed that Res is equally effective against various non- albicans species of Candida as well thereby demonstrating its wide repertoire. Notably, the antifungal effect of Res seems to be independent of the activity of major drug efflux pumps transporter which is the major cause of drug resistance in C. albicans. Finally, we also demonstrated that Res inhibits the serum and nitrogen starvation dependent yeast to hyphal transition in C. albicans which is one of the major virulence attribute. Taken together, Res exhibited promising in vitro antifungal properties and potent inhibitor of yeast to hyphal transition that could be used for the treatment of Candida infections. F...

In earlier years, there was abundance of funds in banks in the form of demand and savings deposit... more In earlier years, there was abundance of funds in banks in the form of demand and savings deposits. Hence, the focus of banks was mainly on asset management. But intense competition and volatility of interest rate due to banking reforms reduced the availability of low-cost funds and therefore, banks focused on liability management as well. These pressures call for structured and comprehensive measures and not just ad hoc action. This is how banks started to concentrate more on the management of both sides of the balance sheet. As a result, the concept of asset-liability management originated in India and introduced in the Indian banking industry since 1st April 1999 to administer the risk management aspects. This paper attempts to optimize assets and liabilities of banks using goal programming technique. Secondary data is collected from annual reports of Allahabad bank from 2010-2019 and RBI website is used for modelling. The findings show that in Allahabad bank, goal programming he...

Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate ... more Pancreatic cancer (PC) is one of the most lethal forms of cancers with 5-year mean survival rate of less than 10%. Most of the PC associated deaths are due to metastasis to secondary sites. Calcium (Ca2+) signaling plays a critical role in regulating hallmarks of cancer progression including cell proliferation, migration and apoptotic resistance. Store operated Ca2+ entry (SOCE) mediated by Orai1/2/3 channels is a highly regulated and ubiquitous pathway responsible for Ca2+ influx into non-excitable cells. In this study, we performed extensive bioinformatic analysis of publicly available datasets and observed that Orai3 expression is inversely associated with the mean survival time of PC patients. Orai3 expression analysis in a battery of PC cell lines corroborated its differential expression profile. We then carried out thorough Ca2+ imaging experiments in 6 PC cell lines and found that Orai3 forms a functional SOCE in PC cells. Our in vitro functional assays show that Orai3 regula...

Molecular Aspects of Medicine

Viral infections are one of the leading causes of human illness. Viruses take over host cell sign... more Viral infections are one of the leading causes of human illness. Viruses take over host cell signaling cascades for their replication and infection. Calcium (Ca2+) is a versatile and ubiquitous second messenger that modulates plethora of cellular functions. In last two decades, a critical role of host cell Ca2+ signaling in modulating viral infections has emerged. Furthermore, recent literature clearly implicates a vital role for the organellar Ca2+ dynamics (influx and efflux across organelles) in regulating virus entry, replication and severity of the infection. Therefore, it is not surprising that a number of viral infections including current SARS-CoV-2 driven COVID-19 pandemic are associated with dysregulated Ca2+ homeostasis. The focus of this review is to first discuss the role of host cell Ca2+ signaling in viral entry, replication and egress. We further deliberate on emerging literature demonstrating hijacking of the host cell Ca2+ dynamics by viruses. In particular, a variety of viruses including SARS-CoV-2 modulate lysosomal and cytosolic Ca2+ signaling for host cell entry and replication. Moreover, we delve into the recent studies, which have demonstrated the potential of several FDA-approved drugs targeting Ca2+ handling machinery in inhibiting viral infections. Importantly, we discuss the prospective of targeting intracellular Ca2+ signaling for better management and treatment of viral pathogenesis including COVID-19. Finally, we highlight the key outstanding questions in the field that demand critical and timely attention.

Indian Journal of Finance and Banking

This study examines the efficiency of the overall Indian banking industry using Data Envelopment ... more This study examines the efficiency of the overall Indian banking industry using Data Envelopment Analysis (DEA) and to perform a comparative efficiency analysis of public, private, and foreign banks using six varied forms. Also, providing ranks to the banks based on their efficiency. The study incorporates BCC output-oriented DEA model using a sample of 50 Indian banks (public banks = 17, private banks = 18, foreign banks = 15) for a period ranging from 2009-10 to 2018-19, hence incorporating the after-effects of the financial crisis and demonetization, this study uses panel data from 2009-10 to 2018-19. The results showed that most of the Indian banks fall on the efficient side or are near to full efficiency. However, public banks outperform private and foreign banks in terms of their average efficiency. Results also specify that the performance of banks is sensitive to input-output variables, units under evaluation, and choice of the model. The current study has just focused on th...

Cell Calcium

Ion channels in particular Calcium (Ca2+) channels play a critical role in physiology by regulati... more Ion channels in particular Calcium (Ca2+) channels play a critical role in physiology by regulating plethora of cellular processes ranging from cell proliferation, differentiation, transcriptional regulation and programmed cell death. One such physiologically important and highly Ca2+ selective channel family is Orai channels consisting of three homologs Orai1, Orai2 and Orai3. Orai channels are responsible for Ca2+ influx across the plasma membrane in response to decrease in Endoplasmic Reticulum (ER) Ca2+ stores. STIM1/STIM2 proteins sense the reduction in ER Ca2+ levels and activate Orai channels for restoring ER Ca2+ as well as for driving cellular functions. This signaling cascade is known as Store Operated Ca2+ Entry (SOCE). Although Orai1 is the ubiquitous SOCE channel protein, Orai2 and Orai3 mediate SOCE in certain specific tissues. Further, mammalian specific homolog Orai3 forms heteromultimeric channel with Orai1 for constituting Arachidonic acid regulated Ca2+ (ARC) channels or arachidonic acid metabolite Leukotriene C4 (LTC4) regulated Ca2+ (LRC) channels. Literature suggests that Orai3 regulates Breast, Prostate, Lung and Gastrointestinal cancers by either forming Store Operated Ca2+ (SOC) or ARC/LRC channels in the cancerous cells but not in healthy tissue. In this review, we would discuss the role of Orai3 in these cancers and would highlight the potential of therapeutic targeting of Orai3 for better management and treatment of cancer. Finally, we will deliberate on key outstanding questions in the field that demand critical attention and further studies.

Development

In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical f... more In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical for both development and regeneration. While the fate-commitment events have distinct transcriptional footprints, fate-biasing is often transitory and metastable, and is thought to be moulded by epigenetic programs. Hence molecular basis of specification is difficult to define. In this study, we establish a role of a histone variant H2a.z.2 in specification of melanocyte lineage from multipotent neural crest cells. Silencing of H2a.z.2 reduces the number of melanocyte precursors in developing zebrafish embryos, and from mouse embryonic stem cells in vitro. We demonstrate that this histone variant occupies nucleosomes in the promoter of key melanocyte determinant Mitf, and enhances its induction. CRISPR-Cas9 based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby our study establishes the role of a histone variant u...

Cell Calcium

Store Operated Ca2+ Entry (SOCE) mediated by Orai channels is a ubiquitous Ca2+ influx pathway th... more Store Operated Ca2+ Entry (SOCE) mediated by Orai channels is a ubiquitous Ca2+ influx pathway that regulates several cellular functions. We have earlier reported that Orai3, the mammalian specific Orai1 homolog, plays a critical role in breast cancer progression. More recently, Orai3 was demonstrated to regulate prostate and lung tumorigenesis. Although the tumorigenic potential of Orai3 is associated with increase in its expression, the molecular machinery regulating its expression remains largely unexplored. Here, by performing extensive bioinformatics analysis and functional studies, we identify and characterize micro-RNAs (miRNAs) that regulate Orai3 expression and function. We demonstrate that miR18a and miR18b positively regulate Orai3 whereas miR34a represses Orai3 expression and function. All these miRs exert their effect on Orai3 by virtue of their direct action on Orai3 3'UTR. These miRs provide novel opportunities for targeting Orai3 for better management of cancer. This study further opens up the possibility of targeting specific Orai homologs by different miRs in tissue and disease specific context.

In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical f... more In the neural crest lineage, progressive fate-restriction and stem cell assignment are critical for both development and regeneration. While the fate-commitment events have distinct transcriptional footprints, fate-biasing is often transitory and metastable, and is thought to be moulded by epigenetic programs. Hence molecular basis of specification is difficult to define. In this study, we establish a role of a histone variant H2a.z.2 in specification of melanocyte lineage from multipotent neural crest cells. Silencing of H2a.z.2 reduces the number of melanocyte precursors in developing zebrafish embryos, and from mouse embryonic stem cells in vitro. We demonstrate that this histone variant occupies nucleosomes in the promoter of key melanocyte determinant Mitf, and enhances its induction. CRISPR-Cas9 based targeted mutagenesis of this gene in zebrafish drastically reduces adult melanocytes, as well as their regeneration. Thereby our study establishes a histone based specification c...

Cell calcium, 2018

Calcium (Ca) signaling plays a critical role in regulating plethora of cellular functions includi... more Calcium (Ca) signaling plays a critical role in regulating plethora of cellular functions including cell survival, proliferation and migration. The perturbations in cellular Ca homeostasis can lead to cell death either by activating autophagic pathways or through induction of apoptosis. Endoplasmic reticulum (ER) is the major storehouse of Ca within cells and a number of physiological agonists mediate ER Ca release by activating IP receptors (IPR). This decrease in ER Ca levels is sensed by STIM, which physically interacts and activates plasma membrane Ca selective Orai channels. Emerging literature implicates a key role for STIM1, STIM2, Orai1 and Orai3 in regulating both cell survival and death pathways. In this review, we will retrospect the work highlighting the role of STIM and Orai homologs in regulating cell death signaling. We will further discuss the rationales that could explain the dual role of STIM and Orai proteins in regulating cell fate decisions.

Copyright © 2014 Jyoti Tanwar et al. This is an open access article distributed under the Creativ... more Copyright © 2014 Jyoti Tanwar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The resistance among various microbial species (infectious agents) to different antimicrobial drugs has emerged as a cause of public health threat all over the world at a terrifying rate. Due to the pacing advent of new resistancemechanisms and decrease in efficiency of treating common infectious diseases, it results in failure ofmicrobial response to standard treatment, leading to prolonged illness, higher expenditures for health care, and an immense risk of death. Almost all the capable infecting agents (e.g., bacteria, fungi, virus, and parasite) have employed high levels of multidrug resistance (MDR) with enhanced morbidity and mortality; thus, they are referred to as “super bugs. ” Although the development of MDR is a natural phen...