Publications by authors named "Syed Shujait Ali"

30 Publications

  • Page 1 of 1

Insights Into Mutations Induced Conformational Changes and Rearrangement of Fe Ion in Gene of to Decipher the Mechanism of Resistance to Pyrazinamide.

Front Mol Biosci 2021 20;8:633365. Epub 2021 May 20.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Pyrazinamide (PZA) is the first-line drug commonly used in treating infections and reduces treatment time by 33%. This prodrug is activated and converted to an active form, Pyrazinoic acid (POA), by Pyrazinamidase (PZase) enzyme. resistance to PZA is the outcome of mutations frequently reported in , , and genes. Among the mentioned genes, mutations contribute to 72-99% of the total resistance to PZA. Thus, considering the vital importance of this gene in PZA resistance, its frequent mutations (D49N, Y64S, W68G, and F94A) were investigated through in-depth computational techniques to put conclusions that might be useful for new scaffolds design or structure optimization to improve the efficacy of the available drugs. Mutants and wild type PZase were used in extensive and long-run molecular dynamics simulations in triplicate to disclose the resistance mechanism induced by the above-mentioned point mutations. Our analysis suggests that these mutations alter the internal dynamics of PZase and hinder the correct orientation of PZA to the enzyme. Consequently, the PZA has a low binding energy score with the mutants compared with the wild type PZase. These mutations were also reported to affect the binding of Fe ion and its coordinated residues. Conformational dynamics also revealed that β-strand two is flipped, which is significant in Fe binding. MM-GBSA analysis confirmed that these mutations significantly decreased the binding of PZA. In conclusion, these mutations cause conformation alterations and deformities that lead to PZA resistance.
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http://dx.doi.org/10.3389/fmolb.2021.633365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174790PMC
May 2021

Computational Modeling of Immune Response Triggering Immunogenic Peptide Vaccine Against the Human Papillomaviruses to Induce Immunity Against Cervical Cancer.

Viral Immunol 2021 May 10. Epub 2021 May 10.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P.R. China.

Papillomaviruses are placed within the family Papillomaviride, and the members of this family have a double-stranded circular DNA genome. Every year, ∼30% of cancers are reported to be human papillomavirus (HPV) related, which represents 63,000 cancers of all infectious agent-induced cancers. HPV16 and HPV18 are reported to be associated with 70% of cervical cancers. The quest for an effective drug or vaccine candidate still continues. In this study, we aim to design B cell and T cell epitope-based vaccine using the two structural major capsid protein L1 and L2 as well as other three important proteins (E1, E2, and E6) against HPV strain 16 (HPV16). We used a computational pipeline to design a multiepitope subunit vaccine and tested its efficacy using computational modeling approaches. Our analysis revealed that the multiepitope subunit vaccine possesses antigenic properties, and using cloning method revealed proper expression and downstream processing of the vaccine construct. Besides this, we also performed immune simulation to check the immune response upon the injection. Our results strongly suggest that this vaccine candidate should be tested immediately for the immune response against the cervical cancer-causing agent. The safety, efficacy, expression, and immune response profiling makes it the first choice for experimental and setup.
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http://dx.doi.org/10.1089/vim.2020.0306DOI Listing
May 2021

Genome-wide screening of vaccine targets prioritization and reverse vaccinology aided design of peptides vaccine to enforce humoral immune response against Campylobacter jejuni.

Comput Biol Med 2021 Jun 18;133:104412. Epub 2021 Apr 18.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, PR China; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China. Electronic address:

Campylobacter jejuni, gram-negative bacteria, is an infectious agent of foodborne disease-causing bloody diarrhea, abdominal pain, fever, Guillain-Barré syndrome (GBS) and Miller Fisher syndrome in humans. Campylobacter spp. with multidrug resistance to fluoroquinolones, tetracycline, and erythromycin are reported. Hence, an effective vaccine candidate would provide long-term immunity against C. jejuni infections. Thus, we used a subtractive proteomics pipeline to prioritize essential proteins, which impart a critical role in virulence, replication and survival. Five proteins, i.e. Single-stranded DNA-binding protein, UPF0324 membrane protein Cj0999c, DNA translocase FtsK, 50S ribosomal protein L22, and 50S ribosomal protein L1 were identified as virulent proteins and selected for vaccine designing. We reported that the multi-epitopes subunit vaccine based on CTL, HTL and B-cell epitopes combination possess strong antigenic properties and associates no allergenic reaction. Further investigation revealed that the vaccine interacts with the immune receptor (TLR-4) and triggered the release of primary and secondary immune factors. Moreover, the CAI and GC contents obtained through codon optimization were reported to be 0.93 and 53% that confirmed a high expression in the selected vector. The vaccine designed in this study needs further scientific consensus and will aid in managing C. jejuni infections.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104412DOI Listing
June 2021

Immunogenomics guided design of immunomodulatory multi-epitope subunit vaccine against the SARS-CoV-2 new variants, and its validation through in silico cloning and immune simulation.

Comput Biol Med 2021 06 24;133:104420. Epub 2021 Apr 24.

Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China. Electronic address:

Reports of the novel and more contagious strains of SARS-CoV-2 originating in different countries have further aggravated the pandemic situation. The recent substitutions in spike protein may be critical for the virus to evade the host's immune system and therapeutics that have already been developed. Thus, this study has employed an immunoinformatics pipeline to target the spike protein of this novel strain to construct an immunogenic epitope (CTL, HTL, and B cell) vaccine against the new variant. Our investigation revealed that 12 different epitopes imparted a critical role in immune response induction. This was validated by an exploration of physiochemical properties and experimental feasibility. In silico and host immune simulation confirmed the expression and induction of both primary and secondary immune factors such as IL, cytokines, and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064902PMC
June 2021

BC-TFdb: a database of transcription factor drivers in breast cancer.

Database (Oxford) 2021 Apr;2021

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.

Transcription factors (TFs) are DNA-binding proteins, which regulate many essential biological functions. In several cancer types, TF function is altered by various direct mechanisms, including gene amplification or deletion, point mutations, chromosomal translocations, expression alterations, as well as indirectly by non-coding DNA mutations influencing the binding of the TF. TFs are also actively involved in breast cancer (BC) initiation and progression. Herein, we have developed an open-access database, BC-TFdb (Breast Cancer Transcription Factors database), of curated, non-redundant TF involved in BC. The database provides BC driver TFs related information including genomic sequences, proteomic sequences, structural data, pathway information, mutations information, DNA binding residues, survival and therapeutic resources. The database will be a useful platform for researchers to obtain BC-related TF-specific information. High-quality datasets are downloadable for users to evaluate and develop computational methods for drug designing against BC. Database URL: https://www.dqweilab-sjtu.com/index.php.
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http://dx.doi.org/10.1093/database/baab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060005PMC
April 2021

Higher infectivity of the SARS-CoV-2 new variants is associated with K417N/T, E484K, and N501Y mutants: An insight from structural data.

J Cell Physiol 2021 Mar 23. Epub 2021 Mar 23.

Department of Bioinformatics and Biological Statistics, Shanghai Jiao Tong University, Shanghai, P.R. China.

The evolution of the SARS-CoV-2 new variants reported to be 70% more contagious than the earlier one is now spreading fast worldwide. There is an instant need to discover how the new variants interact with the host receptor (ACE2). Among the reported mutations in the Spike glycoprotein of the new variants, three are specific to the receptor-binding domain (RBD) and required insightful scrutiny for new therapeutic options. These structural evolutions in the RBD domain may impart a critical role to the unique pathogenicity of the SARS-CoV-2 new variants. Herein, using structural and biophysical approaches, we explored that the specific mutations in the UK (N501Y), South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y), and hypothetical (N501Y-E484K) variants alter the binding affinity, create new inter-protein contacts and changes the internal structural dynamics thereby increases the binding and eventually the infectivity. Our investigation highlighted that the South African (K417N-E484K-N501Y), Brazilian (K417T-E484K-N501Y) variants are more lethal than the UK variant (N501Y). The behavior of the wild type and N501Y is comparable. Free energy calculations further confirmed that increased binding of the spike RBD to the ACE2 is mainly due to the electrostatic contribution. Further, we find that the unusual virulence of this virus is potentially the consequence of Darwinian selection-driven epistasis in protein evolution. The triple mutants (South African and Brazilian) may pose a serious threat to the efficacy of the already developed vaccine. Our analysis would help to understand the binding and structural dynamics of the new mutations in the RBD domain of the Spike protein and demand further investigation in in vitro and in vivo models to design potential therapeutics against the new variants.
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http://dx.doi.org/10.1002/jcp.30367DOI Listing
March 2021

Proteome wide vaccine targets prioritization and designing of antigenic vaccine candidate to trigger the host immune response against the Mycoplasma genitalium infection.

Microb Pathog 2021 Mar 29;152:104771. Epub 2021 Jan 29.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, PR China; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Centre on Antibacterial Resistances, Joint International Research Laboratory of Metabolic & Developmental Sciences and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong, 518055, PR China. Electronic address:

Mycoplasma genitalium is a small size, sexually transmitted bacterial pathogen that causes urethritis in males and cervicitis in females. Being resistant to antibiotics, difficulty in diagnosis, treatment, and control of this cosmopolitan infection, vaccination is the alternating method for its effective management. Herein, this study was conducted to computationally design a multi-epitope vaccine to boost host immune responses against M. genitalium. To achieve the study aim, immunoinformatics approaches were applied to the said pathogen's proteomics sequence data. B and T cell epitopes were projected from the three shortlisted vaccine proteins; MG014, MG015, Hmw3MG317. The final vaccine ensemble comprises cytotoxic and helper T cell epitopes fused through appropriate linkers. The epitopes peptide is then liked to an adjuvant for efficient recognition and processing by the host immune system. The various physicochemical parameters such as allergenicity, antigenicity, theoretical pI, GRAVY, and molecular weight of the vaccine were checked and found safe and effective to be used in post-experimental studies. The stability and binding affinity of the vaccine with the TLR1/2 heterodimer were ensured by performing molecular docking. The best-docked complex was considered, ranked top having the lowest binding energy and strong intermolecular binding and stability. Finally, the vaccine constructs better expression was obtained by in silico cloning into the pET28a (+) vector in Escherichia coli K-12 strain, and immune simulation validated the immune response. In a nutshell, all these approaches lead to developing a multi-epitope vaccine that possessed the ability to induce cellular and antibody-mediated immune responses against the pathogen used.
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http://dx.doi.org/10.1016/j.micpath.2021.104771DOI Listing
March 2021

In silico and in vitro evaluation of kaempferol as a potential inhibitor of the SARS-CoV-2 main protease (3CLpro).

Phytother Res 2021 Jan 15. Epub 2021 Jan 15.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.1002/ptr.6998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013176PMC
January 2021

Development of multi-epitope subunit vaccine for protection against the norovirus' infections based on computational vaccinology.

J Biomol Struct Dyn 2020 Nov 10:1-12. Epub 2020 Nov 10.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P.R. China.

Human Norovirus belongs to a family , and was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as "winter vomiting disease." Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study, capsid protein (A7YK10), small protein (A7YK11), and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. The antigenic and non-allergenic epitopes were selected for the subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA, and rampage servers. The modelled vaccine was docked with TLR-7. The stability of the docked complex was evaluated by MD simulation. To apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1845799DOI Listing
November 2020

Subtractive proteomics and immunoinformatics approaches to explore Bartonella bacilliformis proteome (virulence factors) to design B and T cell multi-epitope subunit vaccine.

Infect Genet Evol 2020 11 12;85:104551. Epub 2020 Sep 12.

Department of Bioinformatics and Biological statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, PR China; State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, Joint Laboratory of International Cooperation in Metabolic and Developmental Sciences, Ministry of Education and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, PR China; Peng Cheng Laboratory, Vanke Cloud City Phase I Building 8, Xili Street, Nashan District, Shenzhen, Guangdong 518055, PR China. Electronic address:

Bartonella bacilliformis a gram-negative facultative aerobe responsible for the Carrion's disease widely distributed in Ecuador, Peru, and Colombia with a high mortality rate when no specific treatment is received. B bacilliformis is transmitted by Sand fly (Lutzomyia verrucarum) to healthy individuals. Immunoinformatic and subtractive proteomics approaches were employed in this study to prioritize the best candidates for vaccine designing. These approaches resulted in five vaccine candidates, flagellar biosynthetic protein (Uniprot ID: A1UTU1), heme exporter protein C (UniProt ID: A1UU82), Cytochrome c-type biogenesis protein (Uniprot ID: A1URZ7), Hemin ABC transporter (Uniprot ID: A1US20) and Phosphatidate cytidylyltransferase (Uniprot ID: A1USE3). The mentioned proteins are antigenic and essential for pathogen survival. A range of immune-informatics tools was applied for the prediction of B and T cell epitopes for the vaccine candidate proteins. In-silico vaccine was constructed using carefully evaluated epitopes and consequently modeled for docking with human Toll-like receptor 4. TLR-4 agonist 50S ribosomal protein L7/L12 (UniproKB ID; P9WHE3) was linked to the vaccine as an adjuvant to boost immune response towards the vaccine. For stability evaluation of the vaccine-TLR-4 docked complex, MD simulations were performed. The final vaccine was back-translated and cloned in Eschericia coli to attain the maximal expression of the vaccine protein. The maximal expression was ensured, and the CAI score of 0.96 was reported. The current vaccine requires future experimental validation to confirm its effectiveness. The vaccine developed will be helpful to protect against B bacilliformis associated infections.
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http://dx.doi.org/10.1016/j.meegid.2020.104551DOI Listing
November 2020

Proteome-wide mapping and reverse vaccinology-based B and T cell multi-epitope subunit vaccine designing for immune response reinforcement against .

J Biomol Struct Dyn 2020 Sep 14:1-15. Epub 2020 Sep 14.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, P.R China.

a prominent pathogen responsible for acute periodontal diseases, is widely studied by the scientific community for its successful evasion of the host immune system. is associated with rheumatoid arthritis, dementia, and Alzheimer's. The pathogen successfully survives itself against the heavy load of conventional antibiotics because of its ability to evade the host immune system. Subtractive proteomics and reverse vaccinology approaches were employed in order to prioritize the best proteins for vaccine designing. Three vaccine candidates with Uniprot ID: Q7MWZ2 (histidine Kinase), Q7MVL1 (Fe (2+) transporter), and Q7MWZ2 (Capsular polysaccharide transport protein) were identified for vaccine designing. These proteins are antigenic and essential for pathogen survival. A wide range of immunoinformatics tools was applied for the prediction of epitopes, B, and T cells, for the vaccine candidate proteins. Molecular docking of the predicted epitopes against the MHC molecules were carried out. vaccine was constructed using carefully evaluated epitopes and consequently modeled for docking with human Toll-like receptor 2. Chain C of Pam3CSK4 (PDB ID; 2Z7X) was linked to the vaccine as an adjuvant to boost immune response towards the vaccine. For stability evaluation of the vaccine-TLR-2 docked complex, Molecular Dynamics simulations were performed. The reverse-translated nucleotide sequence cloned in to attain the maximal expression of the vaccine protein. The maximal expression was ensured by CAI score of 0.96. The current vaccine requires future experimental validation to confirm its effectiveness. The vaccine developed will be helpful to protect against associated infections.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1819423DOI Listing
September 2020

Drug similarity and structure-based screening of medicinal compounds to target macrodomain-I from SARS-CoV-2 to rescue the host immune system: a molecular dynamics study.

J Biomol Struct Dyn 2020 Sep 8:1-15. Epub 2020 Sep 8.

Center for Biotechnology and Microbiology, University of Swat, Swat, Khyber Pakhtunkhwa, Pakistan.

The outbreak of the recent coronavirus (SARS-CoV-2), which causes a severe pneumonia infection, first identified in Wuhan, China, imposes significant risks to public health. Around the world, researchers are continuously trying to identify small molecule inhibitors or vaccine candidates by targeting different drug targets. The SARs-CoV-2 macrodomain-I, which helps in viral replication and hijacking the host immune system, is also a potential drug target. Hence, this study targeted viral macrodomain-I by using drug similarity, virtual screening, docking and re-docking approaches. A total of 64,043 compounds were screened, and potential hits were identified based on the docking score and interactions with the key residues. The top six hits were subjected to molecular dynamics simulation and Free energy calculations and repeated three times each. The per-residue energy decomposition analysis reported that these compounds significantly interact with Asp22, Ala38, Asn40, Val44, Phe144, Gly46, Gly47, Leu127, Ser128, Gly130, Ile131, Phe132 and Ala155 which are the critical active site residues. Here, we also used ADPr as a positive control to compare our results. Our results suggest that our identified hits by using such a complicated computational pipeline could inhibit the SARs-CoV-2 by targeting the macrodomain-1. We strongly recommend the experimental testing of these compounds, which could rescue the host immune system and could help to contain the disease caused by SARs-CoV-2.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1815583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544951PMC
September 2020

Structural insights into the mechanism of RNA recognition by the N-terminal RNA-binding domain of the SARS-CoV-2 nucleocapsid phosphoprotein.

Comput Struct Biotechnol J 2020 12;18:2174-2184. Epub 2020 Aug 12.

State Key Lab of Microbial Metabolism, Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

The emergence of recent SARS-CoV-2 has become a global health issue. This single-stranded positive-sense RNA virus is continuously spreading with increasing morbidities and mortalities. The proteome of this virus contains four structural and sixteen nonstructural proteins that ensure the replication of the virus in the host cell. However, the role of phosphoprotein (N) in RNA recognition, replicating, transcribing the viral genome, and modulating the host immune response is indispensable. Recently, the NMR structure of the N-terminal domain of the Nucleocapsid Phosphoprotein has been reported, but its precise structural mechanism of how the ssRNA interacts with it is not reported yet. Therefore, here, we have used an integrated computational pipeline to identify the key residues, which play an essential role in RNA recognition. We generated multiple variants by using an alanine scanning strategy and performed an extensive simulation for each system to signify the role of each interfacial residue. Our analyses suggest that residues T57A, H59A, S105A, R107A, F171A, and Y172A significantly affected the dynamics and binding of RNA. Furthermore, per-residue energy decomposition analysis suggests that residues T57, H59, S105 and R107 are the key hotspots for drug discovery. Thus, these residues may be useful as potential pharmacophores in drug designing.
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http://dx.doi.org/10.1016/j.csbj.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419326PMC
August 2020

Phylogenetic Analysis and Structural Perspectives of RNA-Dependent RNA-Polymerase Inhibition from SARs-CoV-2 with Natural Products.

Interdiscip Sci 2020 Sep 3;12(3):335-348. Epub 2020 Jul 3.

State Key Lab of Microbial Metabolism, Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Most recently, an outbreak of severe pneumonia caused by the infection of SARS-CoV-2, a novel coronavirus first identified in Wuhan, China, imposes serious threats to public health. Upon infecting host cells, coronaviruses assemble a multi-subunit RNA-synthesis complex of viral non-structural proteins (nsp) responsible for the replication and transcription of the viral genome. Therefore, the role and inhibition of nsp12 are indispensable. A cryo-EM structure of RdRp from SARs-CoV-2 was used to identify novel drugs from Northern South African medicinal compounds database (NANPDB) by using computational virtual screening and molecular docking approaches. Considering Remdesivir as the control, 42 compounds were shortlisted to have docking score better than Remdesivir. The top 5 hits were validated by using molecular dynamics simulation approach and free energy calculations possess strong inhibitory properties than the Remdesivir. Thus, this study paved a way for designing novel drugs by decoding the architecture of an important enzyme and its inhibition with compounds from natural resources. This disclosing of necessary knowledge regarding the screening and the identification of top hits could help to design effective therapeutic candidates against the coronaviruses and design robust preventive measurements.
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http://dx.doi.org/10.1007/s12539-020-00381-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332347PMC
September 2020

Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro).

J Biomol Struct Dyn 2020 Jun 18:1-12. Epub 2020 Jun 18.

State Key Lab of Microbial Metabolism, Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1779128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309305PMC
June 2020

Structural insights of catalytic mechanism in mutant pyrazinamidase of .

J Biomol Struct Dyn 2021 Jun 12;39(9):3172-3185. Epub 2020 May 12.

College of Life Sciences and Biotechnology, The State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University, China.

Pyrazinamidase (PZase) is a member of Fe-dependent amidohydrolases that activates pyrazinamide (PZA) into active pyrazinoic acid (POA). PZA, a nicotinamide analogue, is an essential first-line drug used in (Mtb) treatment. The active form of PZA, POA, is toxic and potently inhibits the growth of latent Mtb, which makes it possible to shorten the conventional 9-month tuberculosis treatment to 6 months. In this study, an extensive molecular dynamics simulation was carried out to the study the resistance mechanism offered by the three mutations Q10P and D12A and G97D. Our results showed that two regions Gln10-His43, Phe50-Gly75 are profoundly affected by these mutations. Among the three mutations, Q10P and D12A mutations strongly disturb the communication among the catalytic triad (Asp8, Lys98 and Cys138). The oxyanion hole is formed between the backbone nitrogen atoms of A134 and C138 which stabilizes the hydroxyl anion of nicotinamide. The D12A mutation greatly disturbs the oxyanion hole formation followed by the Q10P and G97D. Our results also showed that these mutations destabilize the interaction between Fe ion and Asp49, His51, His57 and His71. The binding pocket analysis showed that these mutations increase the cavity volume, which results in loose binding of PZA. MMGBSA analyzes have shown that these mutations reduce the binding affinity to the PZA drug. Our results may provide useful information for the design of new and effective PZase inhibitors based on structural information of WT and mutant PZases.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1761879DOI Listing
June 2021

Effect of Gibberellic Acid on Production of Biomass, Polyphenolics and Steviol Glycosides in Adventitious Root Cultures of (Bert.).

Plants (Basel) 2020 Mar 30;9(4). Epub 2020 Mar 30.

Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad 45320, Pakistan.

In current study, the effect of gibberellic acid was tested for production of biomass, polyphenolics and Steviol glycosides in adventitious root cultures of . Adventitious cultures were induced from the roots of in vitro grown plantlets on Murashige and Skoog (MS) medium containing combination of gibberellic acid (GA; 0.5, 1.0, 1.5 and 2.0 mg/L) and naphthalene acetic acid (NAA; 0.5 mg/L). Initially, a known mass of inoculum roots were shifted into suspension media augmented with various GA concentrations. The growth behavior of adventitious roots was recorded every 3 days for a period of 30 days. Maximum biomass biosynthesis (13.12 g/flask) was noticed in exponential phase on 27th day in the suspension containing 2.0 mg/L of GA. Other GA concentrations also displayed optimum patterns of biomass accumulation as compared to the control. Adventitious roots were investigated for total phenolic content (TPC) and production (TPP), total flavonoid content (TFC) and production (TFP), and 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-based antioxidant potential. Maximum phenolics (TPC 9.84 mg gallic acid equivalent (GAE)/g-dry weight (DW)) and TPP (147.6 mg/L), TFC (5.12 mg Quercitin equivalent (QE)/g-DW) and TFP (76.91 mg/L) were observed in 2.0 mg/L GA treated cultures. The same concentration of gibberellic acid enhanced antioxidant activity (77.2%). Furthermore, maximum stevioside (7.13 mg/g-DW), rebaudioside-A (0.27 mg/g-DW) and dulcoside-A (0.001 mg/g-DW) were observed in roots exposed to 2.0 mg/L GA. This is the first report on the application of GA on biomass accumulation and secondary metabolite production in . The current study will be helpful to scale up the adventitious root cultures in bioreactors for the production of biomass and pharmaceutically important secondary metabolites.
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http://dx.doi.org/10.3390/plants9040420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238111PMC
March 2020

An Integrated Systems Biology and Network-Based Approaches to Identify Novel Biomarkers in Breast Cancer Cell Lines Using Gene Expression Data.

Interdiscip Sci 2020 Jun 13;12(2):155-168. Epub 2020 Feb 13.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.

Breast cancer is the most common cause of death in women worldwide. Approximately 5%-10% of instances are attributed to mutations acquired from the parents. Therefore, it is highly recommended to design more potential drugs and drug targets to eradicate such complex diseases. Network-based gene expression profiling is a suggested tool for discovering drug targets by incorporating various factors such as disease states, intensities based on gene expression as well as protein-protein interactions. To find prospective biomarkers in breast cancer, we first identified differentially expressed genes (DEGs) statistical methods p-value and false discovery rate were initially used. Of the total 82 DEGs, 67 were upregulated while the remaining 17 were downregulated. Sub-modules and hub genes include VEGFA with the highest degree, followed by 15 CCND1 and CXCL8 with 12-degree score was found. The survival analysis revealed that all the hub genes have important role in the development and progression of breast cancer. Enrichment analysis revealed that most of these genes are involved in signaling pathways and in the extracellular spaces. We also identified transcription factors and kinases, which regulate proteins in the DEGs PPI. Finally, drugs for each hub genes were identified. These results further expanded the knowledge regarding important biomarkers in breast cancer.
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http://dx.doi.org/10.1007/s12539-020-00360-0DOI Listing
June 2020

Dynamics Insights Into the Gain of Flexibility by Helix-12 in ESR1 as a Mechanism of Resistance to Drugs in Breast Cancer Cell Lines.

Front Mol Biosci 2019 24;6:159. Epub 2020 Jan 24.

State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Incidents of breast cancer (BC) are on the rise on a daily basis and have proven to be the most prevelant cause of death for women in both developed and developing countries. Among total BC cases diagnosed after menopause, 70% of cases are Estrogen Receptor (ER) positive (ER-positive or ER+). Mutations in the LBD (ligand-binding domain) of the ER have recently been reported to be the major cause of resistance to potent antagonists. In this study, the experimentally reported mutations K303R, E380Q, V392I, S463P, V524E, P535H, P536H, Y537C, Y537N, Y537S, and D538G were analyzed, and the most significant mutations were shortlisted based on multiple analyses. Initial analyses, such as mCSM stability, occluded depth analysis, mCSM-binding affinity, and FoldX energy changes shortlisted only six mutations as being highly resistant. Finally, simulations of force field-based molecular dynamics (MD on wild type (WT) ERα) on six mERα variants (E380Q, S463P, Y537S, Y537C, Y537N, and D538G) were carried out to justify mechanism of the resistance. It was observed that these mutations increased the flexibility of the H12. A bonding analysis suggested that previously reported important residue His524 lost bonding upon mutation. Other parameters, such as PCA (principal component analysis), DCCM (dynamics cross-correlation), and FEL (free energy landscape), verified that the shortlisted mutations affect the H12 helix, which opens up the co-activator binding conformation. These results provide deep insight into the mechanism of relative resistance posed to fulvestrant due to mutations in breast cancer. This study will facilitate further understanding of the important aspects of designing specific and more effective drugs.
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http://dx.doi.org/10.3389/fmolb.2019.00159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992541PMC
January 2020

Over-the-counter medicines in Pakistan: misuse and overuse.

Lancet 2020 01;395(10218):116

Centre for Biotechnology and Microbiology, University of Swat, Swat-19200, Pakistan.

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http://dx.doi.org/10.1016/S0140-6736(19)32999-XDOI Listing
January 2020

Sustainable production of biomass and industrially important secondary metabolites in cell cultures of selfheal ( L.) elicited by silver and gold nanoparticles.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):2553-2561

d Department of Bioinformatics and Biostatistics College of Life Sciences and Biotechnology, The State Key Laboratory of Microbial Metabolism, Shanghai Jiao Tong University , Shanghai , China.

Elicited artificial cultures are gaining more interest due to their uniform biosynthesis of industrially valuable secondary metabolites. In this study, a unique methodology was applied, in which different ratios of gold (Au) and silver (Ag) nanoparticles (NPs) were supplemented to submerge cultures to investigate sustainable production of biomass and antioxidant secondary metabolites. Cell suspension cultures were exposed to Ag and AuNPs alone or different ratios of AgAuNPs (1:2; 1:3; 2:1; 3:1) in combination with NAA. The combination of AgAuNPs (3:1) with NAA enhanced fresh (9.25 g/100 ml) and dry biomass (0.64 g/100 ml) of suspended cells than control (6.67; 0.233 g/100 ml). AuNPs with NAA-augmented media enhanced biomass accumulation in lag, log and stationary phases in a period of 49 days. Furthermore, AgAu (3:1) and AgAuNPs (2:1; 1:2) with NAA enhanced protein contents, peroxidase and superoxide dismutase enzymes. However, maximum phenolics (TPC; 10.61 mg/g-DW) and flavonoids (7.62 mg/g-DW) were observed in cell cultures exposed to a combination of AgAuNPs (1:3) and NAA than control (6.27, 5.49 mg/g-DW). The combination of AgAuNPs (2:1) with NAA enhanced antioxidant activity (87.85%) in cell cultures. This study will help in illuminating the impact of NPs on cultures development and production of natural antioxidants.
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http://dx.doi.org/10.1080/21691401.2019.1625913DOI Listing
December 2019

Immunoinformatics and structural vaccinology driven prediction of multi-epitope vaccine against Mayaro virus and validation through in-silico expression.

Infect Genet Evol 2019 09 4;73:390-400. Epub 2019 Jun 4.

Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address:

The Mayaro virus (MAYV) belongs to genus "Alphavirus" and family "Togaviridae". MAYV has distribution in the Amazonia, Central and Northeastern regions of Brazil. The abundance of mosquito vector Haemagogus janthinomys has major role in the outbreaks of arthralgia disease in Brazil. Vaccination or immunization is an alternative approach for the protection against this disease. To search the effective candidate for vaccine against Mayaro virus, various immunoinformatics tools were used to predict both the B and T cell epitopes from five structural polyproteins (capsid, E2, 6K, E3and E1). A multi subunit vaccine was designed and the final sequence was modeled for docking with TLR-3. Human b defensin based on previous studies was used as linker. The docked complexes of vaccine-TLR-3 were then subjected to dynamics stability and RMSD and RMSF results suggested that the complexes are stable. Further, to validate our final vaccine construct, in silico cloning was carried out using E. coli as host. The CAI value of 0.96 suggests that the vaccine construct properly expresses in the host. The current findings will be useful for the future experimental validations to ratify the immunogenicity and safety of the supposed structure of vaccine, and ultimately to treat the Mayaro virus, associated infections.
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http://dx.doi.org/10.1016/j.meegid.2019.06.006DOI Listing
September 2019

Immunoinformatic and systems biology approaches to predict and validate peptide vaccines against Epstein-Barr virus (EBV).

Sci Rep 2019 01 24;9(1):720. Epub 2019 Jan 24.

State Key Laboratory of Microbial Metabolism, and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Epstein-Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is a member of the Herpesviridae family and causes infectious mononucleosis, Burkitt's lymphoma, and nasopharyngeal carcinoma. Even in the United States of America, the situation is alarming, as EBV affects 95% of the young population between 35 and 40 years of age. In this study, both linear and conformational B-cell epitopes as well as cytotoxic T-lymphocyte (CTL) epitopes were predicted by using the ElliPro and NetCTL.1.2 webservers for EBV proteins (GH, GL, GB, GN, GM, GP42 and GP350). Molecular modelling tools were used to predict the 3D coordinates of peptides, and these peptides were then docked against the MHC molecules to obtain peptide-MHC complexes. Studies of their post-docking interactions helped to select potential candidates for the development of peptide vaccines. Our results predicted a total of 58 T-cell epitopes of EBV;  where the most potential were selected based on their TAP, MHC binding and C-terminal Cleavage score. The top most peptides were subjected to MD simulation and stability analysis. Validation of our predicted epitopes using a 0.45 µM concentration was carried out by using a systems biology approach. Our results suggest a panel of epitopes that could be used to immunize populations to protect against multiple diseases caused by EBV.
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http://dx.doi.org/10.1038/s41598-018-37070-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346095PMC
January 2019

Computational identification, characterization and validation of potential antigenic peptide vaccines from hrHPVs E6 proteins using immunoinformatics and computational systems biology approaches.

PLoS One 2018 1;13(5):e0196484. Epub 2018 May 1.

State Key Laboratory of Microbial Metabolism, and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

High-risk human papillomaviruses (hrHPVs) are the most prevalent viruses in human diseases including cervical cancers. Expression of E6 protein has already been reported in cervical cancer cases, excluding normal tissues. Continuous expression of E6 protein is making it ideal to develop therapeutic vaccines against hrHPVs infection and cervical cancer. Therefore, we carried out a meta-analysis of multiple hrHPVs to predict the most potential prophylactic peptide vaccines. In this study, immunoinformatics approach was employed to predict antigenic epitopes of hrHPVs E6 proteins restricted to 12 Human HLAs to aid the development of peptide vaccines against hrHPVs. Conformational B-cell and CTL epitopes were predicted for hrHPVs E6 proteins using ElliPro and NetCTL. The potential of the predicted peptides were tested and validated by using systems biology approach considering experimental concentration. We also investigated the binding interactions of the antigenic CTL epitopes by using docking. The stability of the resulting peptide-MHC I complexes was further studied by molecular dynamics simulations. The simulation results highlighted the regions from 46-62 and 65-76 that could be the first choice for the development of prophylactic peptide vaccines against hrHPVs. To overcome the worldwide distribution, the predicted epitopes restricted to different HLAs could cover most of the vaccination and would help to explore the possibility of these epitopes for adaptive immunotherapy against HPVs infections.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196484PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929558PMC
August 2018

Allosteric ligands for the pharmacologically important Flavivirus target (NS5) from ZINC database based on pharmacophoric points, free energy calculations and dynamics correlation.

J Mol Graph Model 2018 06 11;82:37-47. Epub 2018 Apr 11.

State Key Laboratory of Microbial Metabolism and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:

Dengue virus belongs to a group of human pathogens, which causes different diseases, dengue hemorrhagic fever and dengue shock syndrome in humans. It possesses RNA as a genetic material and is replicated with the aid of NS5 protein. RNA-dependent RNA polymerase (RdRp) is an important domain of NS5 in the replication of that virus. The catalytic process activity of RdRp is making it an important target for antiviral chemical therapy. To date, No FDA drug has been approved and marketed for the treatment of diseases caused by Dengue virus. So, there is a dire need to advance an area of active antiviral inhibitors that is safe, less expensive and widely available. An experimentally validated complex of Dengue NS5 and compound 27 (6LS) were used as pharmacophoric input and hits were identified. We also used Molecular dynamics (MD) simulations alongside free energy and dynamics of the internal residues of the apo and holo systems to understand the binding mechanism. Our analysis resulted that the three inhibitors (ZINC72070002, ZINC6551486, and ZINC39588257) greatly affected the interior dynamics and residual signaling to dysfunction the replicative role of NS5. The interaction of these inhibitors caused the loss of the correlated motion of NS5 near to the N terminus and helped the stability of the binding complex. This investigation provided a methodological route to discover allosteric inhibitors against the epidemics of this Flaviviruses. Allosteric inhibitors are important and major assets in considering the development of the competitive and robust antiviral agents such as against Dengue viral infection.
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http://dx.doi.org/10.1016/j.jmgm.2018.03.004DOI Listing
June 2018

Pakistan as a major obstacle in global end to poliomyelitis program: background and 2016 update.

Braz J Infect Dis 2016 Sep-Oct;20(5):518-20. Epub 2016 Aug 12.

University of Swat, Center for Biotechnology and Microbiology, Odigram, Pakistan.

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http://dx.doi.org/10.1016/j.bjid.2016.07.009DOI Listing
April 2017

Sucrose-enhanced biosynthesis of medicinally important antioxidant secondary metabolites in cell suspension cultures of Artemisia absinthium L.

Bioprocess Biosyst Eng 2016 Dec 11;39(12):1945-1954. Epub 2016 Aug 11.

Mid-Florida Research and Education Center and Department of Plant Pathology, University of Florida/Institute of Food and Agricultural Sciences, 2725 Binion Rd, Apopka, FL, 32703, USA.

Natural products are gaining tremendous importance in pharmaceutical industry and attention has been focused on the applications of in vitro technologies to enhance yield and productivity of such products. In this study, we investigated the accumulation of biomass and antioxidant secondary metabolites in response to different carbohydrate sources (sucrose, maltose, fructose and glucose) and sucrose concentrations (1, 3, 5, 7 and 9 %). Moreover, the effects of 3 % repeated sucrose feeding (day-12, -18 and -24) were also investigated. The results showed the superiority of disaccharides over monosaccharides for maximum biomass and secondary metabolites accumulation. Comparable profiles for maximum biomass were observed in response to sucrose and maltose and initial sucrose concentrations of 3 and 5 %. Maximum total phenolic and total flavonoid contents were displayed by cultures treated with sucrose and maltose; however, initial sucrose concentrations of 5 and 7 % were optimum for both classes of metabolites, respectively. Following 3 % extra sucrose feeding, cultures fed on day-24 (late-log phase) showed higher biomass, total phenolic and total flavonoid contents as compared to control cultures. Highest antioxidant activity was exhibited by maltose-treated cultures. Moreover, sucrose-treated cultures displayed positive correlation of antioxidant activity with total phenolics and total flavonoids production. This work describes the stimulatory role of disaccharides and sucrose feeding strategy for higher accumulation of phenolics and flavonoids, which could be potentially scaled up to bioreactor level for the bulk production of these metabolites in suspension cultures of A. absinthium.
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http://dx.doi.org/10.1007/s00449-016-1668-8DOI Listing
December 2016

Correlation of different spectral lights with biomass accumulation and production of antioxidant secondary metabolites in callus cultures of medicinally important Prunella vulgaris L.

J Photochem Photobiol B 2016 Jun 11;159:1-7. Epub 2016 Mar 11.

Pakistan Council of Scientific and Industrial Research (PCSIR) Laboratories Complex, Peshawar 25120, Pakistan.

Light is one of the key elicitors that directly fluctuates plant developmental processes and biosynthesis of secondary metabolites. In this study, the effects of various spectral lights on biomass accumulation and production of antioxidant secondary metabolites in callus cultures of Prunella vulgaris were investigated. Among different spectral lights, green light induced the maximum callogenic response (95%). Enhanced fresh biomass accumulation was observed in log phases on day-35, when callus cultures were exposed to yellow and violet lights. Yellow light induced maximum biomass accumulation (3.67g/100ml) from leaf explants as compared to control (1.27g/100ml). In contrast, violet lights enhanced biomass accumulation (3.49g/100ml) from petiole explant. Maximum total phenolics content (TPC; 23.9mg/g-DW) and total flavonoids content (TFC; 1.65mg/g-DW) were observed when cultures were grown under blue lights. In contrast, green and yellow lights enhanced total phenolics production (TPP; 112.52g/100ml) and total flavonoids production (TFP; 9.64g/100ml) as compared to control. The calli grown under green, red and blue lights enhanced DPPH-free radical scavenging activity (DFRSA; 91.3%, 93.1% and 93%) than control (56.44%) respectively. The DFRSA was correlated either with TPC and TFC or TPP and TFP. Furthermore, yellow lights enhanced superoxide dismutase (SOD), peroxidase (POD) and protease activities, however, the content of total protein (CTP) was higher in control cultures (186μg BSAE/mg FW) as compared to spectral lights. These results suggest that the exposure of callus cultures to various spectral lights have shown a key role in biomass accumulation and production of antioxidant secondary metabolites.
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http://dx.doi.org/10.1016/j.jphotobiol.2016.03.008DOI Listing
June 2016

Out of Africa: Miocene dispersal, vicariance, and extinction within Hyacinthaceae subfamily Urgineoideae.

J Integr Plant Biol 2013 Oct 30;55(10):950-64. Epub 2013 Aug 30.

Institute of Plant Sciences, Karl-Franzens-University Graz, Graz, A-8010, Austria; Biocenter Linz, Linz, A-4040, Austria; Institute of Biotechnology and Microbiology, University of Swat, KP, Pakistan.

Disjunct distribution patterns in plant lineages are usually explained according to three hypotheses: vicariance, geodispersal, and long-distance dispersal. The role of these hypotheses is tested in Urgineoideae (Hyacinthaceae), a subfamily disjunctly distributed in Africa, Madagascar, India, and the Mediterranean region. The potential ancestral range, dispersal routes, and factors responsible for the current distribution in Urgineoideae are investigated using divergence time estimations. Urgineoideae originated in Southern Africa approximately 48.9 Mya. Two independent dispersal events in the Western Mediterranean region possibly occurred during Early Oligocene and Miocene (29.9-8.5 Mya) via Eastern and Northwestern Africa. A dispersal from Northwestern Africa to India could have occurred between 16.3 and 7.6 Mya. Vicariance and extinction events occurred approximately 21.6 Mya. Colonization of Madagascar occurred between 30.6 and 16.6 Mya, after a single transoceanic dispersal event from Southern Africa. The current disjunct distributions of Urgineoideae are not satisfactorily explained by Gondwana fragmentation or dispersal via boreotropical forests, due to the younger divergence time estimates. The flattened winged seeds of Urgineoideae could have played an important role in long-distance dispersal by strong winds and big storms, whereas geodispersal could have also occurred from Southern Africa to Asia and the Mediterranean region via the so-called arid and high-altitude corridors.
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http://dx.doi.org/10.1111/jipb.12065DOI Listing
October 2013

Inferences of biogeographical histories within subfamily Hyacinthoideae using S-DIVA and Bayesian binary MCMC analysis implemented in RASP (Reconstruct Ancestral State in Phylogenies).

Ann Bot 2012 Jan 27;109(1):95-107. Epub 2011 Oct 27.

Institute of Plant Sciences, Karl-Franzens-University Graz, Holteigasse 6, A-8010 Graz, Austria.

Background And Aims: Subfamily Hyacinthoideae (Hyacinthaceae) comprises more than 400 species. Members are distributed in sub-Saharan Africa, Madagascar, India, eastern Asia, the Mediterranean region and Eurasia. Hyacinthoideae, like many other plant lineages, show disjunct distribution patterns. The aim of this study was to reconstruct the biogeographical history of Hyacinthoideae based on phylogenetic analyses, to find the possible ancestral range of Hyacinthoideae and to identify factors responsible for the current disjunct distribution pattern.

Methods: Parsimony and Bayesian approaches were applied to obtain phylogenetic trees, based on sequences of the trnL-F region. Biogeographical inferences were obtained by applying statistical dispersal-vicariance analysis (S-DIVA) and Bayesian binary MCMC (BBM) analysis implemented in RASP (Reconstruct Ancestral State in Phylogenies).

Key Results: S-DIVA and BBM analyses suggest that the Hyacinthoideae clade seem to have originated in sub-Saharan Africa. Dispersal and vicariance played vital roles in creating the disjunct distribution pattern. Results also suggest an early dispersal to the Mediterranean region, and thus the northward route (from sub-Saharan Africa to Mediterranean) of dispersal is plausible for members of subfamily Hyacinthoideae.

Conclusions: Biogeographical analyses reveal that subfamily Hyacinthoideae has originated in sub-Saharan Africa. S-DIVA indicates an early dispersal event to the Mediterranean region followed by a vicariance event, which resulted in Hyacintheae and Massonieae tribes. By contrast, BBM analysis favours dispersal to the Mediterranean region, eastern Asia and Europe. Biogeographical analysis suggests that sub-Saharan Africa and the Mediterranean region have played vital roles as centres of diversification and radiation within subfamily Hyacinthoideae. In this bimodal distribution pattern, sub-Saharan Africa is the primary centre of diversity and the Mediterranean region is the secondary centre of diversity. Sub-Saharan Africa was the source area for radiation toward Madagascar, the Mediterranean region and India. Radiations occurred from the Mediterranean region to eastern Asia, Europe, western Asia and India.
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http://dx.doi.org/10.1093/aob/mcr274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241591PMC
January 2012