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result(s) for
"Sakshi Singh"
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GAK and PRKCD are positive regulators of PRKN-independent mitophagy
2021
The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remains elusive. Here, we have screened for regulators of PRKN-independent mitophagy using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as regulators of PRKN-independent mitophagy, with both being dispensable for PRKN-dependent mitophagy and starvation-induced autophagy. We demonstrate that the kinase activity of both GAK and PRKCD are required for efficient mitophagy in vitro, that PRKCD is present on mitochondria, and that PRKCD facilitates recruitment of ULK1/ATG13 to early autophagic structures. Importantly, we demonstrate in vivo relevance for both kinases in the regulation of basal mitophagy. Knockdown of GAK homologue (
gakh-1
) in
C. elegans
or knockout of PRKCD homologues in zebrafish led to significant inhibition of basal mitophagy, highlighting the evolutionary relevance of these kinases in mitophagy regulation.
The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remain elusive. Here the authors use an siRNA library to screen lipid-binding proteins, and identify the kinases GAK and PRKCD as positive regulators of PRKN-independent mitophagy.
Journal Article
The cholesterol transport protein GRAMD1C regulates autophagy initiation and mitochondrial bioenergetics
2022
During autophagy, cytosolic cargo is sequestered into double-membrane vesicles called autophagosomes. The contributions of specific lipids, such as cholesterol, to the membranes that form the autophagosome, remain to be fully characterized. Here, we demonstrate that short term cholesterol depletion leads to a rapid induction of autophagy and a corresponding increase in autophagy initiation events. We further show that the ER-localized cholesterol transport protein GRAMD1C functions as a negative regulator of starvation-induced autophagy and that both its cholesterol transport VASt domain and membrane binding GRAM domain are required for GRAMD1C-mediated suppression of autophagy initiation. Similar to its yeast orthologue, GRAMD1C associates with mitochondria through its GRAM domain. Cells lacking GRAMD1C or its VASt domain show increased mitochondrial cholesterol levels and mitochondrial oxidative phosphorylation, suggesting that GRAMD1C may facilitate cholesterol transfer at ER-mitochondria contact sites. Finally, we demonstrate that expression of GRAMD family proteins is linked to clear cell renal carcinoma survival, highlighting the pathophysiological relevance of cholesterol transport proteins.
The functions of specific lipids in autophagosome biogenesis are not entirely clear. Here, the authors show that the ER protein GRAMD1C, a cholesterol transport protein, suppresses autophagy initiation and has roles in mitochondrial cholesterol homeostasis and respiration.
Journal Article
Recent Strategies for the Remediation of Textile Dyes from Wastewater: A Systematic Review
by
Bala, Saroj
,
Tripathi, Manikant
,
Kasaudhan, Jahnvi
in
Adsorbents
,
Adsorption
,
Aquatic environment
2023
The presence of dye in wastewater causes substantial threats to the environment, and has negative impacts not only on human health but also on the health of other organisms that are part of the ecosystem. Because of the increase in textile manufacturing, the inhabitants of the area, along with other species, are subjected to the potentially hazardous consequences of wastewater discharge from textile and industrial manufacturing. Different types of dyes emanating from textile wastewater have adverse effects on the aquatic environment. Various methods including physical, chemical, and biological strategies are applied in order to reduce the amount of dye pollution in the environment. The development of economical, ecologically acceptable, and efficient strategies for treating dye-containing wastewater is necessary. It has been shown that microbial communities have significant potential for the remediation of hazardous dyes in an environmentally friendly manner. In order to improve the efficacy of dye remediation, numerous cutting-edge strategies, including those based on nanotechnology, microbial biosorbents, bioreactor technology, microbial fuel cells, and genetic engineering, have been utilized. This article addresses the latest developments in physical, chemical, eco-friendly biological and advanced strategies for the efficient mitigation of dye pollution in the environment, along with the related challenges.
Journal Article
Tuberculosis in India: Road to elimination
2019
Provision of digital X-ray preferably enabled with Computer Aided Diagnosis (CAD) and teleradiology services across the health sector, Universal Drug Susceptibility Testing (DST) to at least Rifampicin for all diagnosed TB patients through offer of Cartridge-based nucleic acid amplification test (CBNAAT), a sentinel surveillance system in the country with National TB Institute, Bangalore as the nodal centre and setting up sentinel centres at 10 sites with additional human resource and sequencing equipment and reagents, establishment of 2 additional National Reference Laboratory (NRLs) (West and North-East), National TB Policy and TB Bill, National TB Elimination Board: An apex body to facilitate policy development, implementation etc. Nutritional support to TB patients and families, financial incentives to patients and providers, health system strengthening, and linking patients with existing social and financial support systems of the government, etcAddressing poverty, malnutrition, urbanization, and indoor air pollution.To address gender and other equity issues, special efforts by engaging concerned departments and agencies will be prioritizedNational Airborne Infection Control guideline will be implemented at high-risk centersPatient-centered approach to treatmentReducing the out-of-pocket expenditure for TB patientsLinking Pradhan Mantri Jan-Dhan Yojana, Aadhaar, and Nikshay for direct cash benefits to patientsActive case finding in prisoners, screening at entry to the prisonTB control in hilly and difficult terrainsUniversal DST before initiation of treatment. Government of India should declare TB as a public health emergency and combat it in a campaign modeIncrease budgetary provisions (at present, it is only 3%) and launch a national TB campaign engaging ambassadors at regional level to increase visibilityRebrand RNTCP (name/logo/slogan) to minimize the stigmatizationEngage diverse stakeholders, especially elected representatives and civil society, and establish intersectoral coordinationEmpower and engage TB community – TB patients must not be seen as passive recipients of care, and they should be made key stakeholders at all stages of planning, decision making, implementation, and monitoring.
Journal Article
The future of the future foods: understandings from the past towards SDG-2
2025
Food security faces growing challenges due to population growth, resource limitations, economic pressures, and industrialization-induced lifestyle changes. Traditional food systems struggle to adapt, necessitating innovative solutions and sustainable practices to meet future food demands. This review article explores emerging food system models and alternative food sources, including edible insects, seaweeds, plant-based and lab-cultured meats, underutilized crops, hydroponics, and next-generation fish farming. It highlights the role of food processing technologies such as blockchain, biotechnology, and robotics in enhancing sustainability, reducing waste, and improving food system efficiency. Consumer acceptance of engineered and fortified foods emerges as a critical factor in driving these innovations. The review also emphasizes the need for a transformative approach to food production, incorporating innovative technologies and sustainable practices to ensure food security by 2050. A coordinated effort to integrate alternate food sources and advanced processing methods will be vital for achieving a secure and sustainable global food future.
Journal Article
Carbon Dioxide Separation Technologies: Applicable to Net Zero
by
Chauhan, Geetanjali
,
Singh, Sakshi
,
Pandey, Gaurav
in
Activated carbon
,
Adsorbents
,
Adsorption
2023
Carbon dioxide (CO2) emissions from burning fossil fuels play a crucial role in global warming/climate change. The effective removal of CO2 from the point sources or atmosphere (CO2 capture), its conversion to value-added products (CO2 utilization), and long-term geological storage, or CO2 sequestration, has captured the attention of several researchers and policymakers. This review paper illustrates all kinds of CO2 capture/separation processes and the challenges faced in deploying these technologies. This review described the research efforts put forth in gas separation technologies. Recent advances in the existing gas separation technologies have been highlighted, and future directives for commercial deployment have also been outlined.
Journal Article
Impact of Certification of Competencies on Undergraduate Medical Students
2025
Background A competency-based undergraduate curriculum reinforces the need for certification of certain essential skills. The development of competencies would be the main emphasis of teaching-learning and assessment, which would continue until the target competency was attained. This study was planned to evaluate the impact of certification of competencies among second-year students in the Department of Pharmacology in terms of knowledge and feedback. Methodology After receiving approval from the institutional ethics committee, this study was conducted on MBBS second-year students in the department of pharmacology at a tertiary care teaching hospital in Rajasthan, India. After teaching certifiable competencies in practical class, students were given standardized validated multiple choice questions as pre-tests before certification and post-tests after certification. The feedback was analyzed using a five-point Likert scale questionnaire to assess students' satisfaction and attitude at the end of a session. Results A total of 123 second-year MBBS students who completed both pre- and post-tests were enrolled in the study. The mean score before and after the test was 10.90 ± 2.80 and 13.08 ± 2.90, respectively. There was a statistically significant difference between before and after test scores (p < 0.0001). Conclusion According to the study's findings, the certification of certifiable competencies showed a significant improvement in the performance of students after the intervention. This shows that it played an important part in improving students' knowledge. Thus, it is an effective tool to impart knowledge among students where discussions with faculty and feedback to students play important roles.
Journal Article
Artemisinin derivatives induce oxidative stress leading to DNA damage and caspase-mediated apoptosis in Theileria annulata-transformed cells
by
Bhandari, Vasundhra
,
Suresh, Akash
,
Singh, Sakshi
in
Animals
,
Antibodies
,
Antiparasitic agents
2023
Background
Bovine theileriosis caused by the eukaryotic parasite
Theileria annulata
is an economically important tick-borne disease. If it is not treated promptly, this lymphoproliferative disease has a significant fatality rate. Buparvaquone (BPQ) is the only chemotherapy-based treatment available right now. However, with the emergence of BPQ resistance on the rise and no backup therapy available, it is critical to identify imperative drugs and new targets against
Theileria
parasites.
Methods
Artemisinin and its derivatives artesunate (ARS), artemether (ARM), or dihydroartemisinin (DHART) are the primary defence line against malaria parasites. This study has analysed artemisinin and its derivatives for their anti-
Theileria
l activity and mechanism of action.
Results
ARS and DHART showed potent activity against the
Theileria-
infected cells. BPQ in combination with ARS or DHART showed a synergistic effect. The compounds act specifically on the parasitised cells and have minimal cytotoxicity against the uninfected host cells. Treatment with ARS or DHART induces ROS-mediated oxidative DNA damage leading to cell death. Further blocking intracellular ROS by its scavengers antagonised the anti-parasitic activity of the compounds. Increased ROS production induces oxidative stress and DNA damage causing
p53
activation followed by caspase-dependent apoptosis in the
Theileria-
infected cells.
Conclusions
Our findings give unique insights into the previously unknown molecular pathways underpinning the anti-
Theileria
l action of artemisinin derivatives, which may aid in formulating new therapies against this deadly parasite.
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Video abstract
Journal Article
A comprehensive overview of biodegradable packaging films: Part I—sources, additives, and preparation methods
2025
The present review aims to analyze biodegradable packaging films, with a specific emphasis on their sources, the role of additives in enhancing their properties and functionality, and the processes involved in their development. While traditional biodegradable films are derived primarily from polysaccharides, proteins, lipids, or hydrocolloids, recent advancements have led to the incorporation of natural and synthetic additives to enhance their mechanical, barrier, and functional properties. The integration of nanocomposites, bioactive compounds, and plant-based extracts has significantly improved the antimicrobial, antioxidant, and physical characteristics of these films. Processing techniques such as extrusion and solution casting have also evolved to produce biodegradable films with properties comparable to those of conventional plastics, enabling large-scale production. Therefore, the current trends and prospects identified in this review could offer valuable insights to facilitate the adoption of sustainable practices within the food industry. Moreover, the findings can contribute to ongoing efforts in the innovation and advancement of eco-friendly biodegradable packaging materials.
Journal Article
Simulation studies, 3D QSAR and molecular docking on a point mutation of protein kinase B with flavonoids targeting ovarian Cancer
2021
Background
Ovarian cancer is the world’s dreaded disease and its prevalence is expanding globally. The study of integrated molecular networks is crucial for the basic mechanism of cancer cells and their progression. During the present investigation, we have examined different flavonoids that target protein kinases B (AKT1) protein which exerts their anticancer efficiency intriguing the role in cross-talk cell signalling, by metabolic processes through
in-silico
approaches.
Method
Molecular dynamics simulation (MDS) was performed to analyze and evaluate the stability of the complexes under physiological conditions and the results were congruent with molecular docking. This investigation revealed the effect of a point mutation (W80R), considered based on their frequency of occurrence, with AKT1 protein.
Results
The ligand with high docking scores and favourable behaviour on dynamic simulations are proposed as potential W80R inhibitors. A virtual screening analysis was performed with 12,000 flavonoids satisfying Lipinski’s rule of five according to which drug-likeness is predicted based on its pharmacological and biological properties to be active and taken orally. The pharmacokinetic ADME (adsorption, digestion, metabolism, and excretion) studies featured drug-likeness. Subsequently, a statistically significant 3D-QSAR model of high correlation coefficient (R2) with 0.822 and cross-validation coefficient (Q2) with 0.6132 at 4 component PLS (partial least square) were used to verify the accuracy of the models. Taxifolin holds good interactions with the binding domain of W80R, highest Glide score of − 9.63 kcal/mol with OH of GLU
234
and H bond ASP
274
and LEU
156
amino acid residues and one pi-cation interaction and one hydrophobic bond with LYS
276
.
Conclusion
Natural compounds have always been a richest source of active compounds with a wide variety of structures, therefore, these compounds showed a special inspiration for medical chemists. The present study has aimed molecular docking and molecular dynamics simulation studies on taxifolin targeting W80R mutant protein of protein kinase B/serine- threonine kinase/AKT1 (EC:2.7.11.1) protein of ovarian cancer for designing therapeutic intervention. The expected result supported the molecular cause in a mutant form which resulted in a gain of ovarian cancer. Here we discussed validations computationally and yet experimental evaluation or in vivo studies are endorsed for further study. Several of these compounds should become the next marvels for early detection of ovarian cancer.
Journal Article