Department of Biological Sciences

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14K prolactin derived 14-mer antiangiogenic peptide targets bradykinin-/nitric oxide-cGMP-dependent angiogenesis
(FEBS Press, 2024-09) Majumder, Syamantak
Over the past few decades, VEGF-targeted antiangiogenic therapy for cancers has gained increasing attention. Nevertheless, there are still several limitations such as the potential resistance mechanisms arising in cancer cells against these therapies and their potential adverse effects. These limitations highlight the need for novel anti-angiogenesis molecules and better understanding of the mechanisms of tumor angiogenesis. In the present study, we investigated the antiangiogenic properties of a novel 14-mer antiangiogenic peptide (14-MAP) derived from N-terminal 14 kDa buffalo prolactin and characterized its mode of action. 14-MAP at the picomolar concentration inhibited VEGF- and bradykinin (an autacoid peptide expressed in vascular tissues in pathophysiology, BK)-stimulated endothelial nitric oxide (eNO) production, cell migration, and proliferation in endothelial cells and vessel development in the chick embryo. Although this peptide inhibited both VEGF- and BK-dependent angiogenic processes, its action was more pronounced in the latter. Moreover, the interference of 14-MAP with the eNO synthase (eNOS)-cyclic GMP pathway was also identified. A combination of a low dose of Avastin, a widely used drug targeting VEGF-dependent angiogenesis, and 14-MAP significantly reduced tumor size in an in vivo model of human colon cancer. Taken together, our results suggest that 14-MAP, a BK- and eNOS-dependent antiangiogenic peptide, might be useful for overcoming the limitation of VEGF-targeted antiangiogenic therapy in cancer patients. However, further studies will be required to further characterize its mode of action and therapeutic potential.
2 - Signaling cross talk between biotic and abiotic stress responses in soybean
(Academic Press, 2016) Sharma, Rita
Biotic and abiotic stresses take a heavy toll on crop productivity in soybean (Glycine max (L.) Merr.). To deal with this problem, considerable efforts have been made to understand the molecular mechanism underlying stress perception and tolerance in response to both biotic and abiotic stresses. Recent advances have highlighted several candidate genes that are involved in tolerance to more than one type of stress and, therefore, affect the outcome of the stress response. In this chapter, we summarize the current knowledge about the key transcription factors and signaling components known to regulate stress cross talk in soybean. In total, twenty genes have been demonstrated to confer tolerance to multiple stresses using transgenic approaches. However, to date, only three genes including GmERF3, GmERF057, and GmCAM4 are known to confer tolerance to both biotic and abiotic stresses. Further, in addition to the key genes, the potential of microRNAs and mycorrhiza in engineering broad spectrum stress-tolerant soybean varieties has been discussed.
807-P2 - Pseudomonas syringae produces an inhibitor of a plant defence-related Beta-galactosidase
(IS-MPMI XVIII Congress, 2019-07) Chandrasekar, Balakumaran
During infection, plants and bacteria participate in a dynamic interaction in the apoplast. Secreted hydrolases are among the prominent players in plant defence and are therefore targets of virulence factors. Using Nicotiana benthamiana and Pseudomonas syringae pv. tomato (Pst) DC3000 as a model system, we recently discovered a plant β-galactosidase (BGAL1) that functions in immunity against bacteria by facilitating the hydrolytic release of elicitor peptides from glycosylated flagellin, which activates plant defences. Interestingly, PstDC3000 produce an inhibitor of BGAL1. Here, we identify the biosynthetic gene cluster that is responsible for BGAL1 inhibitor production, which is under the control of type III secretion system regulators hrpR/S/L. Mutant bacteria lacking this gene cluster show reduced virulence in N. benthamiana. Comparative genomics suggests acquisition of this gene cluster via horizontal gene transfer and indicates a correlation between inhibitor production and the identity of flagellin glycans. Partial purification and characterization of the inhibitor has revealed that it is a hydrophilic, heat stable and basic small molecule, similar to a sugar derivative. Our work has uncovered a novel small molecule virulence factor that is secreted into the apoplast to inhibit a plant defence-related enzyme and highlights the role of glycans and apoplastic enzymes in plant-pathogen interactions.
Ab initio Folding Simulation of the Trp-cage Mini-protein Approaches NMR Resolution
(Elsiever, 2003-03-28) Chowdhury, Shibasish
Here, we report a 100 ns molecular dynamics simulation of the folding process of a recently designed autonomous-folding mini-protein designated as tc5b with a new AMBER force field parameter set developed based on condensed-phase quantum mechanical calculations and a Generalized Born continuum solvent model. Starting from its fully extended conformation, our simulation has produced a final structure resembling that of NMR native structure to within 1 Å main-chain root mean square deviation. Remarkably, the simulated structure stayed in the native state for most part of the simulation after it reached the state. Of greater significance is that our simulation has not only reached the correct main-chain conformation, but also a very high degree of accuracy in side-chain packing conformation. This feat has traditionally been a challenge for ab initio simulation studies. In addition to characterization of the trajectory, comparison of our results to experimental data is also presented. Analysis of the trajectory suggests that the rate-limiting step of folding of this mini-protein is the packing of the Trp side-chain.
Aberrant expression of col14a1, celrs3, and cthrc1 in breast cancer сells
(Experimental oncology, 2023) Dubey, Uma S.
Collagens, which are the major components of the extracellular matrix involved in the regulation of tumor microenvironment, could be differentially expressed in breast cancer (BC) with different transcriptome profiling. Aim: To analyze the transcript level expression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, COL14A1, CTHRC1, and CELRS3 genes and the clinical relevance of their differential expression in BC. Materials and Methods: The transcript level expression of the genes was analyzed using the quantitative real-time PCR (qPCR) in tumor tissue of 60 BC patients. Results: Overexpression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, CTHRC, and CELRS3 anddown-regulated expression of COL14A1 were observed. COL14A1 down-regulation was associated with aggressive, basal, and Her-2/neu BC subtypes (p = 0.031). Overexpression of CELSR3 was found to be associated with the older age of the patients (> 55 years, p = 0.049). Further analysis with the TCGA BC data set has shown a concordance in the differential expression of the above genes. Furthermore, overexpression of CTHRC1 was associated with poor overall survival (OS), particularly with poor prognosis (p = 0.00042) for the luminal BC subtype. On the other hand, CELSR3 overexpression was associated with mucinous tumors and poor prognosis in post-menopausal women. In silicotarget prediction identified several BC-associated miRNAs and members of miR-154, -515, and -10 families to perform a likely regulatory role in the above ECM genes. Conclusion: The present study shows that the expression of COL14A1 and CTHRC1 may serve as potential biological markers for the detection of basal BC and the prognosis of survival for patients with the luminal subtype of BC.
ACC deaminase producing rhizobacterium Enterobacter cloacae ZNP-4 enhance abiotic stress tolerance in wheat plant
(PLOS Biology, 2022-05) Jha, Prabhat Nath
Plant growth promoting rhizobacterium (PGPR) designated as ZNP-4, isolated from the rhizosphere of Ziziphus nummularia, was identified as Enterobacter cloacae following 16S rRNA sequence analysis. The isolated strain exhibited various plant growth promoting (PGP) traits. The 1-aminocyclopropane-1-carboxylic acid deaminase (ACCD) activity was evaluated under diverse physiological conditions that could be useful for minimizing the abiotic stress-induced inhibitory effects on wheat plants. The strain showed resistance to salt (NaCl) and metal (ZnSO4) stress. The effect of E. cloacae ZNP-4 on the augmentation of plant growth was studied under salinity stress of 150 mM (T1 treatment) & 200 mM (T2 treatment) NaCl. The inoculation of strain ZNP-4 significantly improved the various growth parameters of wheat plant such as shoot length (41%), root length (31%), fresh weight (28%), dry weight (29%), photosynthetic pigments chlorophyll a (62%) and chlorophyll b (34%). Additionally, the strain was found to be efficient for minimizing the imposed Zn stress in terms of improving plant growth, biomass and photosynthetic pigments in pots containing different levels of metal stress of 150 mg kg-1 (treatment T1) and 250 mg kg-1 (treatment T2). Isolate ZNP-4 also improved the proline content and decreased malondialdehyde (MDA) level under both salinity and metal stress, therefore maintaining the membrane integrity. Furthermore, bacterial inoculation increased the activities of antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX). The positive effects of PGPR occurred concurrently with the decrease in abiotic stress-induced reactive oxygen species (ROS) molecules such as hydrogen peroxide (H2O2) and superoxide (O2-) contents. Overall, the observed results indicate that use of bacteria with such beneficial traits could be used as bio-fertilizers for many crops growing under stress conditions.
Activated pericyte attenuates endothelial functions: nitric oxide – cGMP rescues activated pericyte-associated endothelial dysfunctions
(CSP, 2007-11-23) Majumder, Syamantak
Hepatic stellate cells are liver-specific pericytes and exist in close proximity with endothelial cells. The activation of liver pericytes is intrinsic to liver pathogenesis, and leads to endothelial dysfunction, including the low bioavailability of nitric oxide (NO). However, the role of nitric oxide in pericyte–endothelium cross-talk has not yet been elucidated. This work examines the cellular mechanism of action of NO in pericyte-mediated endothelial dysfunction. We used in vitro coculture and conditioned medium systems to study the effects of activated liver pericytes on endothelial function, and an egg yolk vascular bed model was used to study the effects of activated pericytes on angiogenesis. This study also demonstrates that activated pericytes attenuate the migration, proliferation, permeability, and NO production of endothelial cells. Our results demonstrate that activated pericytes restrict angiogenesis in egg yolk vascular bed models, and NO supplementation recovers 70% of the inhibition. Our results also demonstrate that supplementation with NO, sildenafil citrate (phosphodiesterase inhibitor), and 8-bromo-cGMP (cGMP analog) partially recovers activated-pericyte-mediated endothelium dysfunction. We conclude that NO–cGMP alleviates activated-pericyte-associated endothelial dysfunction, including angiogenesis, in a cGMP-dependent
Activation of JNK signaling mediates amyloid-ß-dependent cell death
(Plos One, 2011-09) Tare, Meghana
Alzheimer's disease (AD) is an age related progressive neurodegenerative disorder. One of the reasons for Alzheimer's neuropathology is the generation of large aggregates of Aß42 that are toxic in nature and induce oxidative stress, aberrant signaling and many other cellular alterations that trigger neuronal cell death. However, the exact mechanisms leading to cell death are not clearly understood.
Activity-based protein profiling of hydrolytic enzymes induced by gibberellic acid in isolated aleurone layers of malting barley
(Wiley, 2016-07) Chandrasekar, Balakumaran
During barley germination, the aleurone layer secretes most of the enzymes required to degrade the endosperm, many of which are yet to be characterized. We used activity-based protein profiling (ABPP) to detect a range of active enzymes extracted from aleurone layers isolated from grains of a commercial malting barley variety incubated with or without gibberellic acid (GA). Enzymes found to be induced by GA were putative aleurains, cathepsin-B-like proteases and serine hydrolases. By using an inhibitory sugar panel, a specific active retaining β-glycosidase in the barley aleurone was identified as a putative xylanase. Our results show that ABPP can be used rapidly to identify a variety of active enzyme isoforms in cereal aleurone without the need for enzyme purification.
Activity-based protein profiling of hydrolytic enzymes induced by gibberellic acid in isolated aleurone layers of malting barley
(Wiley, 2016-07) Chandrasekar, Balakumaran
During barley germination, the aleurone layer secretes most of the enzymes required to degrade the endosperm, many of which are yet to be characterized. We used activity-based protein profiling (ABPP) to detect a range of active enzymes extracted from aleurone layers isolated from grains of a commercial malting barley variety incubated with or without gibberellic acid (GA). Enzymes found to be induced by GA were putative aleurains, cathepsin-B-like proteases and serine hydrolases. By using an inhibitory sugar panel, a specific active retaining β-glycosidase in the barley aleurone was identified as a putative xylanase. Our results show that ABPP can be used rapidly to identify a variety of active enzyme isoforms in cereal aleurone without the need for enzyme purification.
Adhesion stimulates Scar/WAVE phosphorylation in mammalian cells
(Taylor & Francis, 2020-12) Singh, Shashi Prakash
The Scar/WAVE complex catalyzes the protrusion of pseudopods and lamellipods, and is therefore a principal regulator of cell migration. However, it is unclear how its activity is regulated, beyond a dependence on Rac. Phosphorylation of the proline-rich region, by kinases such as Erk2, has been suggested as an upstream activator. We have recently reported that phosphorylation is not required for complex activation. Rather, it occurs after Scar/WAVE has been activated, and acts as a modulator. Neither chemoattractant signaling nor Erk2 affects the amount of phosphorylation, though in Dictyostelium it is promoted by cell-substrate adhesion. We now report that cell-substrate adhesion also promotes Scar/WAVE2 phosphorylation in mammalian cells, suggesting that the process is evolutionarily conserved.
Adsorption of Acid Red 66 Dye from Aqueous Solution by Green Microalgae Acutodesmus obliquus Strain PSV2 Isolated from an Industrial Polluted Site
(Scientific Research, 2014-06) Verma, Sanjay Kumar
In the present study, Acutodesmus obliquus strain PSV2 was isolated from a textile and dyeing industrial site and investigated as a cost effective and potential adsorbent for Acid red 66 dye. Batch kinetic experiments were carried out as a function of pH (1.0 - 6.0), contact time (0 - 180 min) and initial dye concentration (10 - 50 mg/L) to determine the decolorization efficiency of microalgae. The maximum adsorption of dye was observed at pH 2.0 during the initial 60 min of contact time. The Langmuir and Freundlich adsorption isotherms were applied to experimental data to investigate the efficiency of adsorbent and mechanism of adsorption. It was observed that Langmuir and Freundlich isotherm fitted well with Acid Red 66 dye data. Langmuir isotherm, described maximum adsorption of dye (44.24 mg/g) with good correlation coefficient (r2 = 0.980) while Freundlich isotherm showed a high correlation coefficient (r2 = 0.994) with value of n greater than unity (n = 1.27). The present study showed that Acutodesmus obliquus strain PSV2 is an eco friendly and highly efficient adsorbent for removal of acid red 66 dye from dyeing and textile industrial wastewater.
Advances in Biotechnology: A Practical Approach (Biotechnology in Agriculture, Industry and Medicine)
(‎ Nova Science Publishers, 2013) Jha, Prabhat N.
Biotechnology is the use of living organisms to enhance products, our lives and our environment. It is a broad and complex discipline that encompasses many specialised areas. The promise that biotechnology holds for developing countries is well recognised and it is an important tool that can be applied to diverse economic sectors with a focus on the production of food crops, livestock management, human health care, the chemical industry and environmental management. This book covers applications of biotechnology in selected areas such as health care, agriculture, microbial systems, "in silico" analysis for drug designing and drug discovery and the environment
Advances in using non-thermal plasmas for healthier crop production: toward pesticide and chemical fertilizer-free agriculture
(Springer, 2025-04) Joshi, Mukul
There is an urgent need to transform agricultural practices to meet the challenges of sustainable food production amidst global population growth and environmental degradation. Traditional crop production methods heavily rely on pesticides and synthetic fertilizers, which pose significant risks to human health, disrupt ecosystems, and contribute to environmental pollution. Moreover, these methods are increasingly unsustainable due to rising costs and diminishing effectiveness, evolving pest resistance, and climate change impacts. Recently, non-thermal plasma (NTP) technology has emerged as a promising alternative for seed treatment in agriculture. NTP uses low-temperature plasma to modify seed surfaces, enhancing germination, vigor, and overall plant growth. Studies have demonstrated that NTP treatment improves nutrient uptake, increases disease resistance, and reduces the reliance on chemical inputs (pesticides and fertilizers), thereby promoting pesticide and chemical fertilizer-free agriculture. This paper explores recent research advancements in NTP seed treatment and its potential applications in sustainable agriculture. By exploring the mechanisms underlying the NTP effects on seed physiology, the paper provides a comprehensive understanding of how this technology can contribute to sustainable crop production. Furthermore, the paper discusses the strengths, weaknesses, opportunities, and challenges associated with the potential large-scale use of low-temperature plasmas in agriculture, aiming to accelerate the adoption of NTP and its commercialization in the agro-food industries. Overall, the goal of this paper is to highlight the transformative potential of NTP seed treatment in achieving healthier crop production that is environmentally friendly, economically viable, and capable of meeting the food demands of a growing global population.
Adventitious root formation in crops—Potato as an example
(Wiley, 2020-12) Joshi, Mukul
The root system of potato is made up of adventitious roots (AR) that form at the base of a sprout once it emerges from the mother tuber. By definition, AR originate from dormant preformed meristems, or from cells neighboring vascular tissues in stems or leaves. This may occur as part of the developmental program of the plant (e.g., potato), or when replacing the embryonic primary roots in response to stress conditions, such as flooding, nutrient deprivation, or wounding. AR formation is studied mainly in cereals and model plants, and less is known about its developmental program in root and tuber crops. In this review, we summarize the recent data on AR development in potato and relate this knowledge to what is known from model plants. For example, AR formation following stem cutting in potato follows a pattern of initiation, expression, and emergence phases that are known for other plants and involves auxin, the master regulator of AR induction and development. Molecular regulation of AR formation and the effect of environmental stresses are discussed. Understanding the origin and nature of AR systems in important crops will contribute to increased production and improve global food security.
Adventitious root formation in crops—Potato as an example
(Wiley, 2020-12-10) Joshi, Mukul
The root system of potato is made up of adventitious roots (AR) that form at the base of a sprout once it emerges from the mother tuber. By definition, AR originate from dormant preformed meristems, or from cells neighboring vascular tissues in stems or leaves. This may occur as part of the developmental program of the plant (e.g., potato), or when replacing the embryonic primary roots in response to stress conditions, such as flooding, nutrient deprivation, or wounding. AR formation is stud- ied mainly in cereals and model plants, and less is known about its developmental program in root and tuber crops. In this review, we summarize the recent data on AR development in potato and relate this knowledge to what is known from model plants. For example, AR formation following stem cutting in potato follows a pattern of initiation, expression, and emergence phases that are known for other plants and involves auxin, the master regulator of AR induction and development. Molecular regulation of AR formation and the effect of environmental stresses are discussed. Understanding the origin and nature of AR systems in important crops will contribute to increased production and improve global food security.
Aggregation induced emission’ active iridium(iii) complexes with applications in mitochondrial staining
(RSC, 2017) Chowdhury, Rajdeep; Laskar, Inamur Rahaman
Two new bis-cyclometalated iridium(III) complexes, [Ir(F2ppy)2(L)] and [Ir(ppy)2(L)], where F2ppy = 2-(2′,4′-difluoro)phenylpyridine, ppy = 2-phenylpyridine and L = 1,2-((pyridin-2-ylimino)methyl)phenol, have been designed and synthesized by a convenient route. We have univocally characterized their structure by 1H NMR, 19F NMR, HRMS and SXRD. Both complexes exhibit strong ‘Aggregation Induced Emission (AIE)’ activity, which has been investigated using spectroscopy measurements, ab initio quantum chemical calculations and by analysing their crystal packing. One of the complexes has been shown to have a potential application as a non-toxic bio-imaging probe for mitochondrial staining.
Aggregation induced phosphorescence’ active iridium(iii) complexes for integrated sensing and inhibition of bacterial growth in aqueous solution
(RSC, 2015) Panwar, Jitendra; Laskar, Inamur Rajaman; Chakraborty, Shamik
The present study attempts to develop a sensitive method to utilize ‘aggregation induced phosphorescence (AIP)’ active iridium(III) complexes as potential agents for “integrated” sensing and inhibition of bacterial growth in aqueous systems. The utilization of iridium(III) complexes for microbial detection in bodies of water has been demonstrated using Escherichia coli (E. coli) as a representative bacterial strain. The tested iridium(III) complexes also exhibited antibacterial properties against representative Gram positive and Gram negative bacterial strains with minimum inhibitory concentration (MIC) values of 4 and 8 μg mL−1, respectively. Microscopic observations indicated that these complexes could penetrate into the bacterial cells and result in subsequent cell death. Preliminary mechanistic studies showed that the DNA binding ability of the iridium(III) complexes is responsible for their antibacterial properties. The observed “dual” role in detection as well as inhibition of bacterial growth makes this study highly promising and encouraging for the exploration of the applicability of other less expensive metal complexes for monitoring and controlling the bacterial levels in drinking and sea water systems at a commercial level.
Agrobacterium-mediated transient transformation of sorghum leaves for accelerating functional genomics and genome editing studies
(Springer Nature, 2020-02) Sharma, Rita
Sorghum is one of the most recalcitrant species for transformation. Considering the time and effort required for stable transformation in sorghum, establishing a transient system to screen the efficiency and full functionality of vector constructs is highly desirable.
Agrobacterium-mediated transient transformation of sorghum leaves for accelerating functional genomics and genome editing studies
(Springer Nature, 2020) Sharma, Rita
Sorghum is one of the most recalcitrant species for transformation. Considering the time and effort required for stable transformation in sorghum, establishing a transient system to screen the efficiency and full functionality of vector constructs is highly desirable.