Structural and functional characterization of genes and enzymes involved in withanolide biosynthesis in Physalis alkekengi L.

Physalis alkekengi L. is recognized as a significant source of various secondary metabolites, particularly C steroidal lactones known as withanolides and physalins, renowned for their therapeutic properties with a rich history in traditional medicine. In this study, we characterized the sequences of key downstream genes (PaFPPS, PaSQS, PaSQE, PaCAS, PaHYD1, and PaDWF5-1) involved in the biosynthesis of withanolides, marking the first characterization of these genes in P.

Secretomic Insights into the Pathophysiology of : The Causative Agent of Scab, a Devastating Apple Tree Disease.

Apple scab, caused by , is one of the world's most commercially significant apple diseases. The fungi have a catastrophic impact on apples, causing considerable losses in fruit quality and productivity in many apple-growing locations despite numerous control agents. Fungi secrete various effectors and other virulence-associated proteins that suppress or alter the host's immune system, and several such proteins were discovered in this work.

Discovery of a New Donepezil-like Acetylcholinesterase Inhibitor for Targeting Alzheimer's Disease: Computational Studies with Biological Validation.

Alzheimer's disorder is one of the most common worldwide health problems, and its prevalence continues to increase, thereby straining the healthcare budgets of both developed and developing countries. So far, donepezil is the only Food and Drug Administration-approved dual-binding site inhibitor of acetylcholinesterase (AChE) that can amplify the cholinergic activity and also decrease Aβ aggregation in Alzheimer patients. We report herein a new donepezil-like natural compound derivative (D1) as a convincing AChE inhibitor.

C. elegans protein interaction network analysis probes RNAi validated pro-longevity effect of nhr-6, a human homolog of tumor suppressor Nr4a1.

Protein-protein interaction (PPI) studies are gaining momentum these days due to the plethora of various high-throughput experimental methods available for detecting PPIs. Proteins create complexes and networks by functioning in harmony with other proteins and here in silico network biology hold the promise to reveal new functionality of genes as it is very difficult and laborious to carry out experimental high-throughput genetic screens in living organisms. We demonstrate this approach by computationally screening C.

Computational insights into the active structure of SGK1 and its implication for ligand design.

Serum- and glucocorticoid-inducible kinase 1 (SGK1), a protein kinase, shares significant structural similarity with other members of the AGC protein kinase family. It has been reported that the inactive SGK1 structure lacks αC helix and this unique feature makes it distinct from other protein kinases. Activation of SGK1 by PDK1 requires phosphorylation at Thr256, but the structural insights of the activation remain unclear.

Withanolide A extends the lifespan in human EGFR-driven cancerous Caenorhabditis elegans.

The conserved EGFR pathway is linked with multiple cancers in humans including breast, ovarian, and lung carcinoma. Withanolide A, one of the major withanolidal active compounds isolated from the Withania somnifera, extends lifespan and ameliorates stress resistance in wild-type C. elegans by targeting the Insulin/IGF-1 signaling pathway.

Withanolide A offers neuroprotection, ameliorates stress resistance and prolongs the life expectancy of Caenorhabditis elegans.

Withanolide A (steroidal lactone) forms the major constituent of the most popular herbal drug in Ayurvedic medicine, Ashwagandha. It has been used since ancient times as an alternative medicine for the treatment of a variety of age related disorders. Here we provide multiple lines of evidence indicating that Withanolide A improves healthspan, delays age-associated physiological changes and also extends the lifespan of Caenorhabditis elegans.

Sequence-based approach for rapid identification of cross-clade CD8+ T-cell vaccine candidates from all high-risk HPV strains.

Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer.

Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans.

Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans.

Understanding the mechanism of atovaquone drug resistance in Plasmodium falciparum cytochrome b mutation Y268S using computational methods.

The rapid appearance of resistant malarial parasites after introduction of atovaquone (ATQ) drug has prompted the search for new drugs as even single point mutations in the active site of Cytochrome b protein can rapidly render ATQ ineffective. The presence of Y268 mutations in the Cytochrome b (Cyt b) protein is previously suggested to be responsible for the ATQ resistance in Plasmodium falciparum (P. falciparum).

Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans.

Beta-caryophyllene (BCP) is a natural bicyclic sesquiterpene and is a FDA approved food additive, found as an active ingredient in essential oils of numerous edible plants. It possesses a wide range of biological activities including anti-oxidant, anti-inflammatory, anti-cancerous and local anesthetic actions. We used the well established Caenorhabditis elegans model system to elucidate the stress modulatory and lifespan prolonging action of BCP.

In silico accelerated identification of structurally conserved CD8+ and CD4+ T-cell epitopes in high-risk HPV types.

Primary approach to prevent cervical cancer includes the development of human papillomavirus (HPV) vaccines. Currently available HPV vaccines (Gardasil and Cervarix) predominantly consider HPV16 and HPV18 strains. However, due to ignorance of the other high-risk strains aside from HPV16 and HPV18 during vaccine development, the critical need is to synthesize a vaccine with possible protection against all the high-risk HPV types.

Comparative analysis of mesothelial invasion by single- and multi-wall carbon nanotubes using computational approach.

This study explored the interactions of carbon nanotubes (CNTs) with mesothelial cells. We carried out molecular dynamic simulation studies on the mesothelial cell invasion by single and multi walled carbon nanotubes. In our simulation experiments SWCNTs showed greater binding affinity with membrane in comparison to MWCNTs with similar aspect ratio.

In silico identification of novel protective VSG antigens expressed by Trypanosoma brucei and an effort for designing a highly immunogenic DNA vaccine using IL-12 as adjuvant.

African trypanosomiasis continues to be a major health problem, with more adults dying from this disease world-wide. As the sequence diversity of Trypanosoma brucei is extreme, with VSGs having 15-25% identity with most other VSGs, hence it displays a huge diversity of adaptations and host specificities. Therefore the need for an improved vaccine has become an international priority.

In silico proteomic characterization of human epidermal growth factor receptor 2 (HER-2) for the mapping of high affinity antigenic determinants against breast cancer.

Multiple different approaches are being used to activate the immune system against breast cancer. Vaccine therapy in general follows the principle that injections of various substances ultimately result in the presentation of tumor peptides to the patient's immune system. We proposed a potential in silico DNA vaccine against breast cancer by integrating high affinity T cell (MHC-I and MHC-II) and B cell (continuous and discontinuous) epitopes.

Identification of immunogenic consensus T-cell epitopes in globally distributed influenza-A H1N1 neuraminidase.

Antigenic drift is the ability of the swine influenza virus to undergo continuous and progressive changes in response to the host immune system. These changes dictate influenza vaccine updates annually to ensure inclusion of antigens of the most current strains. The identification of those peptides that stimulate T-cell responses, termed T-cell epitopes, is essential for the development of successful vaccines.

In silico CD4+ T-cell epitope prediction and HLA distribution analysis for the potential proteins of Neisseria meningitidis Serogroup B--a clue for vaccine development.

Neisseria meningitidis, an exclusive human pathogen, is a major cause of mortality due to meningococcal meningitis and sepsis in many developing countries. Three meningococcal serogroup B proteins, i.e.

Development of resistance against blackleg disease in Brassica oleracea var. botrytis through in silico methods.

Blackleg caused by Leptosphaeria maculans is a very important disease worldwide and causes large yield loss of significant vegetable crops of Brassicaceae family. Absence of resistant 'B' genome in vegetable Brassica oleracea proposed these species susceptible to blackleg disease. We present a specific piece of molecular modelling work, combining in silico docking methods, energy minimization calculations and in silico cloning, to develop a rational peptide as a candidate that functions as a resistance inducing agent against L.

Virtual screening of specific chemical compounds by exploring E.coli NAD+-dependent DNA ligase as a target for antibacterial drug discovery.

Unique substrate specificity compared with ATP-dependent human DNA ligases recommends E.coli NAD(+)-ligases as potential targets. A plausible strategy is to identify the structural components of bacterial DNA ligase that interact with NAD(+) and then to isolate small molecules that recognize these components and thereby block the binding of NAD(+) to the ligase.

In silico designing and optimization of anti-breast cancer antibody mimetic oligopeptide targeting HER-2 in women.

Overexpression of HER-2 is of frequent (20-30%) occurrence in breast cancer. Therapeutic targeting of HER-2 with humanized antibody derived oligopeptide may be a promising approach to the treatment of breast cancer. HER-2 gene is part of a family of genes that play critical roles in regulating transmembrane growth of breast cancer cells.

In silico DNA vaccine designing against human papillomavirus (HPV) causing cervical cancer.

HPV vaccines available in the market are not effective against different strains of papillomavirus, therefore, there is a need to develop a new prophylactic DNA vaccine which can work against different strains of HPVs and may lead to protection of cervical cancer against new pandemic viruses. We designed a potential prophylactic DNA vaccine by using all the consensus epitopic sequences of HPVs L2 capsid protein and performed in silico cloning of multiepitopic antigenic DNA sequence in pVAX-1 vector. Immunogenicity of vaccine has been enhanced by techniques like codon optimization, engineering CpG motifs, introducing promoters and co-injection with plasmids expressing immune-stimulatory molecules.