Publications

@article{BABY2024168738,

title = {The Host miR-17-92 Cluster Negatively Regulates Mouse Mammary Tumor Virus (MMTV) Replication Primarily Via Cluster Member miR-92a},

author = {Jasmin Baby and Bushra Gull and Waqar Ahmad and Hala Abdul Baki and Thanumol Abdul Khader and Neena G. Panicker and Shaima Akhlaq and T. A. Rizvi and Farah Mustafa},

url = {https://www.sciencedirect.com/science/article/pii/S0022283624003474},

doi = {https://doi.org/10.1016/j.jmb.2024.168738},

issn = {0022-2836},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {Journal of Molecular Biology},

volume = {436},

number = {20},

pages = {168738},

abstract = {The mouse mammary tumor virus (MMTV) is a well-known causative agent of breast cancer in mice. Previously, we have shown that MMTV dysregulates expression of the host miR-17-92 cluster in MMTV-infected mammary glands and MMTV-induced tumors. This cluster, better known as oncomiR-1, is frequently dysregulated in cancers, particularly breast cancer. In this study, our aim was to uncover a functional interaction between MMTV and the cluster. Our results reveal that MMTV expression led to dysregulation of the cluster in both mammary epithelial HC11 and HEK293T cells with the expression of miR-92a cluster member being affected the most. Conversely, overexpression of the whole or partial cluster significantly repressed MMTV expression. Notably, overexpression of cluster member miR-92a alone repressed MMTV expression to the same extent as overexpression of the complete/partial cluster. Inhibition of miR-92a led to nearly a complete restoration of MMTV expression, while deletion/substitution of the miR-92a seed sequence rescued MMTV expression. Dual luciferase assays identified MMTV genomic RNA as the potential target of miR-92a. These results show that the miR-17-92 cluster acts as part of the cell’s well-known miRNA-based anti-viral response to thwart incoming MMTV infection. Thus, this study provides the first evidence highlighting the biological significance of host miRNAs in regulating MMTV replication and potentially influencing tumorigenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1371/journal.pbio.3002827,

title = {MMTV RNA packaging requires an extended long-range interaction for productive Gag binding to packaging signals},

author = {Suresha G. Prabhu and Vineeta N. Pillai and Lizna Mohamed Ali and Valérie Vivet-Boudou and Akhil Chameettachal and Serena Bernacchi and Farah Mustafa and Roland Marquet and T. A. Rizvi},

url = {https://doi.org/10.1371/journal.pbio.3002827},

doi = {10.1371/journal.pbio.3002827},

year  = {2024},

date = {2024-01-01},

urldate = {2024-01-01},

journal = {PLOS Biology},

volume = {22},

number = {10},

pages = {1-34},

publisher = {Public Library of Science},

abstract = {The packaging of genomic RNA (gRNA) into retroviral particles relies on the specific recognition by the Gag precursor of packaging signals (Psi), which maintain a complex secondary structure through long-range interactions (LRIs). However, it remains unclear whether the binding of Gag to Psi alone is enough to promote RNA packaging and what role LRIs play in this process. Using mouse mammary tumor virus (MMTV), we investigated the effects of mutations in 4 proposed LRIs on gRNA structure and function. Our findings revealed the presence of an unsuspected extended LRI, and hSHAPE revealed that maintaining a wild-type–like Psi structure is crucial for efficient packaging. Surprisingly, filter-binding assays demonstrated that most mutants, regardless of their packaging capability, exhibited significant binding to Pr77Gag, suggesting that Gag binding to Psi is insufficient for efficient packaging. Footprinting experiments indicated that efficient RNA packaging is promoted when Pr77Gag binds to 2 specific sites within Psi, whereas binding elsewhere in Psi does not lead to efficient packaging. Taken together, our results suggest that the 3D structure of the Psi/Pr77Gag complex regulates the assembly of viral particles around gRNA, enabling effective discrimination against other viral and cellular RNAs that may also bind Gag efficiently.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Krishnan2023,

title = {Identification of a putative Gag binding site critical for feline immunodeficiency virus genomic RNA packaging},

author = {A. Krishnan and L. M. Ali and Suresha G Prabhu and V. N. Pillai and A. Chameettachal and Valérie Vivet-Boudou and Serena Bernacchi and F. Mustafa and Roland Marquet and T. A. Rizvi},

doi = {10.1261/rna.079840.123},

issn = {1469-9001},

year  = {2024},

date = {2024-01-00},

urldate = {2024-01-00},

journal = {RNA},

volume = {30},

number = {1},

pages = {68--88},

publisher = {Cold Spring Harbor Laboratory},

abstract = {The retroviral Gag precursor plays a central role in the selection and packaging of viral genomic RNA (gRNA) by binding to virus-specific packaging signal(s) (psi or ψ). Previously, we mapped the feline immunodeficiency virus (FIV) ψ to two discontinuous regions within the 5′ end of the gRNA that assumes a higher order structure harboring several structural motifs. To better define the region and structural elements important for gRNA packaging, we methodically investigated these FIV ψ sequences using genetic, biochemical, and structure–function relationship approaches. Our mutational analysis revealed that the unpaired U85CUG88 stretch within FIV ψ is crucial for gRNA encapsidation into nascent virions. High-throughput selective 2′ hydroxyl acylation analyzed by primer extension (hSHAPE) performed on wild type (WT) and mutant FIV ψ sequences, with substitutions in the U85CUG88 stretch, revealed that these mutations had limited structural impact and maintained nucleotides 80–92 unpaired, as in the WT structure. Since these mutations dramatically affected packaging, our data suggest that the single-stranded U85CUG88 sequence is important during FIV RNA packaging. Filter-binding assays performed using purified FIV Pr50Gag on WT and mutant U85CUG88 ψ RNAs led to reduced levels of Pr50Gag binding to mutant U85CUG88 ψ RNAs, indicating that the U85CUG88 stretch is crucial for ψ RNA–Pr50Gag interactions. Delineating sequences important for FIV gRNA encapsidation should enhance our understanding of both gRNA packaging and virion assembly, making them potential targets for novel retroviral therapeutic interventions, as well as the development of FIV-based vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37145095,

title = {Differentially-regulated miRNAs in COVID-19: A systematic review},

author = {Waqar Ahmad and Bushra Gull and Jasmin Baby and Neena G Panicker and Thanumol A Khader and Shaima Akhlaq and T. A. Rizvi and F. Mustafa},

doi = {10.1002/rmv.2449},

issn = {1099-1654},

year  = {2023},

date = {2023-07-01},

urldate = {2023-07-01},

journal = {Rev Med Virol},

volume = {33},

number = {4},

pages = {e2449},

abstract = {Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease of 2019 (COVID-19) that infected more than 760 million people worldwide with over 6.8 million deaths to date. COVID-19 is one of the most challenging diseases of our times due to the nature of its spread, its effect on multiple organs, and an inability to predict disease prognosis, ranging from being completely asymptomatic to death. Upon infection, SARS-CoV-2 alters the host immune response by changing host-transcriptional machinery. MicroRNAs (miRNAs) are regarded as post-transcriptional regulators of gene expression that can be perturbed by invading viruses. Several in vitro and in vivo studies have reported such dysregulation of host miRNA expression upon SARS-CoV-2 infection. Some of this could occur as an anti-viral response of the host to the viral infection. Viruses themselves can counteract that response by mounting their own pro-viral response that facilitates virus infection, an aspect which may cause pathogenesis. Thus, miRNAs could serve as possible disease biomarkers in infected people. In the current review, we have summarised and analysed the existing data about miRNA dysregulation in patients infected with SARS-CoV-2 to determine their concordance between studies, and identified those that could serve as potential biomarkers during infection, disease progression, and death, even in people with other co-morbidities. Having such biomarkers can be vital in not only predicting COVID-19 prognosis, but also the development of novel miRNA-based anti-virals and therapeutics which can become invaluable in case of the emergence of new viral variants with pandemic potential in the future.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37243196,

title = {Global Down-regulation of Gene Expression Induced by Mouse Mammary Tumor Virus (MMTV) in Normal Mammary Epithelial Cells},

author = {Waqar Ahmad and Neena G Panicker and Shaima Akhlaq and Bushra Gull and Jasmin Baby and Thanumol A Khader and T. A. Rizvi and F. Mustafa},

doi = {10.3390/v15051110},

issn = {1999-4915},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Viruses},

volume = {15},

number = {5},

abstract = {Mouse mammary tumor virus (MMTV) is a  that causes breast cancer in mice. The mouse mammary epithelial cells are the most permissive cells for MMTV, expressing the highest levels of virus upon infection and being the ones later transformed by the virus due to repeated rounds of infection/superinfection and integration, leading eventually to mammary tumors. The aim of this study was to identify genes and molecular pathways dysregulated by MMTV expression in mammary epithelial cells. Towards this end, mRNAseq was performed on normal mouse mammary epithelial cells stably expressing MMTV, and expression of host genes was analyzed compared with cells in its absence. The identified differentially expressed genes (DEGs) were grouped on the basis of gene ontology and relevant molecular pathways. Bioinformatics analysis identified 12 hub genes, of which 4 were up-regulated (Angp2, Ccl2, Icam, and Myc) and 8 were down-regulated (Acta2, Cd34, Col1a1, Col1a2, Cxcl12, Eln, Igf1, and Itgam) upon MMTV expression. Further screening of these DEGs showed their involvement in many diseases, especially in breast cancer progression when compared with available data. Gene Set Enrichment Analysis (GSEA) identified 31 molecular pathways dysregulated upon MMTV expression, amongst which the PI3-AKT-mTOR was observed to be the central pathway down-regulated by MMTV. Many of the DEGs and 6 of the 12 hub genes identified in this study showed expression profile similar to that observed in the PyMT mouse model of breast cancer, especially during tumor progression. Interestingly, a global down-regulation of gene expression was observed, where nearly 74% of the DEGs in HC11 cells were repressed by MMTV expression, an observation similar to what was observed in the PyMT mouse model during tumor progression, from hyperplasia to adenoma to early and late carcinomas. Comparison of our results with the Wnt1 mouse model revealed further insights into how MMTV expression could lead to activation of the Wnt1 pathway independent of insertional mutagenesis. Thus, the key pathways, DEGs, and hub genes identified in this study can provide important clues to elucidate the molecular mechanisms involved in MMTV replication, escape from cellular anti-viral response, and potential to cause cell transformation. These data also validate the use of the MMTV-infected HC11 cells as an important model to study early transcriptional changes that could lead to mammary cell transformation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN25,

title = {Understanding Retroviral Life Cycle and its Genomic RNA Packaging},

author = {A. Chameettachal and F. Mustafa and T. A. Rizvi},

doi = {10.1016/j.jmb.2022.167924},

issn = {0022-2836},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {J Mol Biol},

volume = {435},

number = {3},

pages = {167924},

abstract = {Members of the family Retroviridae are important animal and human pathogens. Being obligate parasites, their replication involves a series of steps during which the virus hijacks the cellular machinery. Additionally, many of the steps of retrovirus replication are unique among viruses, including reverse transcription, integration, and specific packaging of their genomic RNA (gRNA) as a dimer. Progress in retrovirology has helped identify several molecular mechanisms involved in each of these steps, but many are still unknown or remain controversial. This review summarizes our present understanding of the molecular mechanisms involved in various stages of retrovirus replication. Furthermore, it provides a comprehensive analysis of our current understanding of how different retroviruses package their gRNA into the assembling virions. RNA packaging in retroviruses holds a special interest because of the uniqueness of packaging a dimeric genome. Dimerization and packaging are highly regulated and interlinked events, critical for the virus to decide whether its unspliced RNA will be packaged as a "genome" or translated into proteins. Finally, some of the outstanding areas of exploration in the field of RNA packaging are highlighted, such as the role of epitranscriptomics, heterogeneity of transcript start sites, and the necessity of functional polyA sequences. An in-depth knowledge of mechanisms that interplay between viral and cellular factors during virus replication is critical in understanding not only the virus life cycle, but also its pathogenesis, and development of new antiretroviral compounds, vaccines, as well as retroviral-based vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN115,

title = {Expression, purification, and functional characterization of soluble recombinant full-length simian immunodeficiency virus (SIV) Pr55(Gag)},

author = {V. N. Pillai and L. M. Ali and S. G. Prabhu and A. Krishnan and S. Tariq and F. Mustafa and T. A. Rizvi},

doi = {10.1016/j.heliyon.2023.e12892},

issn = {2405-8440 (Print) 2405-8440},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Heliyon},

volume = {9},

number = {1},

pages = {e12892},

abstract = {The simian immunodeficiency virus (SIV) precursor polypeptide Pr55(Gag) drives viral assembly and facilitates specific recognition and packaging of the SIV genomic RNA (gRNA) into viral particles. While several studies have tried to elucidate the role of SIV Pr55(Gag) by expressing its different components independently, studies using full-length SIV Pr55(Gag) have not been conducted, primarily due to the unavailability of purified and biologically active full-length SIV Pr55(Gag). We successfully expressed soluble, full-length SIV Pr55(Gag) with His(6)-tag in bacteria and purified it using affinity and gel filtration chromatography. In the process, we identified within Gag, a second in-frame start codon downstream of a putative Shine-Dalgarno-like sequence resulting in an additional truncated form of Gag. Synonymously mutating this sequence allowed expression of full-length Gag in its native form. The purified Gag assembled into virus-like particles (VLPs) in vitro in the presence of nucleic acids, revealing its biological functionality. In vivo experiments also confirmed formation of functional VLPs, and quantitative reverse transcriptase PCR demonstrated efficient packaging of SIV gRNA by these VLPs. The methodology we employed ensured the availability of >95% pure, biologically active, full-length SIV Pr55(Gag) which should facilitate future studies to understand protein structure and RNA-protein interactions involved during SIV gRNA packaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN23,

title = {Detection of SARS-CoV-2 in COVID-19 Patient Nasal Swab Samples Using Signal Processing},

author = {M. A. Ahmad and L. J. A. Olule and M. Meetani and F. A. Sheikh and R. A. Blooshi and N. G. Panicker and F. Mustafa and T. A. Rizvi},

doi = {10.1109/jstsp.2021.3134073},

issn = {1932-4553 (Print) 1932-4553},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {IEEE J Sel Top Signal Process},

volume = {16},

number = {2},

pages = {164-174},

abstract = {This work presents an opto-electrical method that measures the viral nucleocapsid protein and anti-N antibody interactions to differentiate between SARS-CoV-2 negative and positive nasal swab samples. Upon light exposure of the patient nasal swab sample mixed with the anti-N antibody, charge transfer (CT) transitions within the altered protein folds are initiated between the charged amino acids side chain moieties and the peptide backbone that play the role of donor and acceptor groups. A Figure of Merit (FOM) was introduced to correlate the relative variations of the samples with and without antibody at two different voltages. Empirically, SARS-CoV-2 in patient nasal swab samples was detected within two minutes, if an extracted FOM threshold of >1 was achieved; otherwise, the sample wasconsidered negative.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN37,

title = {Comparative Experimental Investigation of Biodegradable Antimicrobial Polymer-Based Composite Produced by 3D Printing Technology Enriched with Metallic Particles},

author = {W. Ahmed and A. H. Al-Marzouqi and M. H. Nazir and T. A. Rizvi and E. Zaneldin and M. Khan},

doi = {10.3390/ijms231911235},

issn = {1422-0067},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Int J Mol Sci},

volume = {23},

number = {19},

abstract = {Due to the prevailing existence of the COVID-19 pandemic, novel and practical strategies to combat pathogens are on the rise worldwide. It is estimated that, globally, around 10% of hospital patients will acquire at least one healthcare-associated infection. One of the novel strategies that has been developed is incorporating metallic particles into polymeric materials that neutralize infectious agents. Considering the broad-spectrum antimicrobial potency of some materials, the incorporation of metallic particles into the intended hybrid composite material could inherently add significant value to the final product. Therefore, this research aimed to investigate an antimicrobial polymeric PLA-based composite material enhanced with different microparticles (copper, aluminum, stainless steel, and bronze) for the antimicrobial properties of the hybrid composite. The prepared composite material samples produced with fused filament fabrication (FFF) 3D printing technology were tested for different time intervals to establish their antimicrobial activities. The results presented here depict that the sample prepared with 90% copper and 10% PLA showed the best antibacterial activity (99.5%) after just 20 min against different types of bacteria as compared to the other samples. The metallic-enriched PLA-based antibacterial sheets were remarkably effective against Staphylococcus aureus and Escherichia coli; therefore, they can be a good candidate for future biomedical, food packaging, tissue engineering, prosthetic material, textile industry, and other science and technology applications. Thus, antimicrobial sheets made from PLA mixed with metallic particles offer sustainable solutions for a wide range of applications where touching surfaces is a big concern.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN63,

title = {Impact of the Sinopharm's BBIBP-CorV vaccine in preventing hospital admissions and death in infected vaccinees: Results from a retrospective study in the emirate of Abu Dhabi, United Arab Emirates (UAE)},

author = {F. Ismail AlHosani and A. Eduardo Stanciole and B. Aden and A. Timoshkin and O. Najim and W. Abbas Zaher and F. AlSayedsaleh AlDhaheri and S. Al Mazrouie and T. A. Rizvi and F. Mustafa},

doi = {10.1016/j.vaccine.2022.02.039},

issn = {0264-410X (Print) 0264-410x},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Vaccine},

volume = {40},

number = {13},

pages = {2003-2010},

abstract = {BACKGROUND: This is a community-based, retrospective, observational study conducted to determine effectiveness of the BBIBP-CorV inactivated vaccine in the real-world setting against hospital admissions and death. STUDY DESIGN: Study participants were selected from 214,940 PCR-positive cases of COVID-19 reported to the Department of Health, Abu Dhabi Emirate, United Arab Emirates (UAE) between September 01, 2020 and May 1, 2021. Of these, 176,640 individuals were included in the study who were aged ≥ 15 years with confirmed COVID-19 positive status who had records linked to their vaccination status. Those with incomplete or missing records were excluded (n = 38,300). Study participants were divided into three groups depending upon their vaccination status: fully vaccinated (two doses), partially vaccinated (single dose), and non-vaccinated. Study outcomes included COVID-19-related admissions to hospital general and critical care wards and death. Vaccine effectiveness for each outcome was based on the incidence density per 1000 person-years. RESULTS: The fully-, partially- and non-vaccinated groups included 62,931, 21,768 and 91,941 individuals, respectively. Based on the incidence rate ratios, the vaccine effectiveness in fully vaccinated individuals was 80%, 92%, and 97% in preventing COVID-19-related hospital admissions, critical care admissions, and death, respectively, when compared to the non-vaccinated group. No protection was observed for critical and non-critical care hospital admissions for the partially vaccinated group, while some protection against death was apparent, although statistically insignificant. CONCLUSIONS: In a COVID-19 pandemic, use of the Sinopharm BBIBP-CorV inactivated vaccine is effective in preventing severe disease and death in a two-dose regimen. Lack of protection with the single dose may be explained by insufficient seroconversion and/or neutralizing antibody responses, behavioral factors (i.e., false sense of protection), and/or other biological factors (emergence of variants, possibility of reinfection, duration of vaccine protection, etc.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN17,

title = {Early Years of Carbapenem-Resistant Enterobacterales Epidemic in Abu Dhabi},

author = {T. Pál and A. B. Butt and A. Ghazawi and J. Thomsen and T. A. Rizvi and Á Sonnevend},

doi = {10.3390/antibiotics11101435},

issn = {2079-6382 (Print) 2079-6382},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Antibiotics (Basel)},

volume = {11},

number = {10},

abstract = {Recent studies showed that the current endemic of carbapenem-resistant Enterobacterales (CRE) in the Emirate of Abu Dhabi is dominated by highly resistant Klebsiella pneumoniae clones ST14, ST231, and CC147, respectively. In the absence of continuous, molecular typing-based surveillance, it remained unknown whether they lately emerged and rapidly became dominant, or they had been present from the early years of the endemic. Therefore, antibiotic resistance, the presence of carbapenemase and 16S methylase genes, and the sequence types of CRE strains collected between 2009 and 2015 were compared with those collected between 2018 and 2019. It was found that members of these three clones, particularly those of the most prevalent ST14, started dominating already in the very early years of the CRE outbreak. Furthermore, while severely impacting the overall antibiotic resistance patterns, the effect of these clones was not exclusive: for example, increasing trends of colistin or decreasing rates of tigecycline resistance were also observed among nonclonal isolates. The gradually increasing prevalence of few major, currently dominating clones raises the possibility that timely, systematic, molecular typing-based surveillance could have provided tools to public health authorities for an early interference with the escalation of the local CRE epidemic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN30,

title = {The first nationwide surveillance of carbapenem-resistant Enterobacterales in the United Arab Emirates - increased association of Klebsiella pneumoniae CC14 clone with Emirati patients},

author = {Á Sonnevend and N. Abdulrazzaq and A. Ghazawi and J. Thomsen and G. Bharathan and L. Makszin and T. A. Rizvi and T. Pál},

doi = {10.1016/j.ijid.2022.04.034},

issn = {1201-9712},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Int J Infect Dis},

volume = {120},

pages = {103-112},

abstract = {OBJECTIVES: To assess the current prevalence, distribution, and main clonal types of carbapenem-resistant Enterobacterales (CRE) in the United Arab Emirates. METHODS: A total of 504 CRE collected over a 9-month period in 15 hospitals were studied. Antibiotic susceptibility and the presence of common carbapenemase, 16S methylase, and mobile colistin resistance genes were assessed. Selected strains forming larger clusters by pulsed field gel electrophoresis were subjected to whole genome sequencing to identify their sequence types and core genome MLST. RESULTS: Strains expressing OXA and NDM type carbapenemases and 16S methylases were present in all major hospitals. Considerable interhospital differences were noticed, suggesting the role of specific clones. A total of three major Klebsiella pneumoniae clones (CC14, ST231, and CC147) were identified, accounting for 48.6% of all CRE. All clones were significantly more resistant than sporadic isolates. CC14 strains exhibited a significant association with Emirati patients. CONCLUSIONS: Nearly half of CRE infections in the country are due to a limited number of clones. The data indicate the possibility of interhospital transmission, combined in some hospitals with inadequate stewardship practices. The study also revealed an association of the largest, most resistant clone (CC14) with Emirati patients. The specific reasons for it should be clarified by further investigations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN31,

title = {Molecular Characterization of MCR-1 Producing Enterobacterales Isolated in Poultry Farms in the United Arab Emirates},

author = {Á Sonnevend and W. Q. Alali and S. A. Mahmoud and A. Ghazawi and G. Bharathan and S. Melegh and T. A. Rizvi and T. Pál},

doi = {10.3390/antibiotics11030305},

issn = {2079-6382 (Print) 2079-6382},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Antibiotics (Basel)},

volume = {11},

number = {3},

abstract = {Data on the prevalence of MCR-producing Enterobacterales of animal origin are scarce from the Arabian Peninsula. We investigated the presence and variety of such strains from fecal specimens of poultry collected in four farms in the United Arab Emirates. Colonies from ten composite samples per farm grown on colistin-supplemented plates were PCR-screened for alleles of the mcr gene. Thirty-nine isolates selected based on species, colony morphology, and plasmid profile were subjected to whole genome sequencing. The panel of their resistance and virulence genes, MLST and cgMLST were established. Transferability and incompatibility types of the MCR-plasmids were determined. mcr-1.1 positive strains were identified in 36 of the 40 samples. Thirty-four multi-drug resistant Escherichia coli of 16 different sequence types, two Escherichia albertii, two Klebsiella pneumoniae and one Salmonella minnesota were identified. Beyond various aminoglycoside, tetracycline, and co-trimoxazole resistance genes, seven of them also carried ESBL genes and one bla(CMY-2). Six IncHI2, 26 IncI2 and 4 IncX4 MCR-plasmids were mobilized, in case of the IncHI2 plasmids co-transferring ampicillin, chloramphenicol and tetracycline resistance. The diversity of mcr-1 positive strains suggest a complex local epidemiology calling for a coordinated surveillance including animals, retail meat and clinical cases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN14,

title = {Optical Detection of SARS-CoV-2 Utilizing Antigen-Antibody Binding Interactions},

author = {M. A. Ahmad and F. Mustafa and N. Panicker and T. A. Rizvi},

doi = {10.3390/s21196596},

issn = {1424-8220},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Sensors (Basel)},

volume = {21},

number = {19},

abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease (COVID-19) pandemic, is sweeping the world today. This study investigates the optical detection of SARS-CoV-2, utilizing the antigen-antibody binding interactions utilizing a light source from a smart phone and a portable spectrophotometer. The proof-of-concept is shown by detecting soluble preparations of spike protein subunits from SARS-CoV-2, followed by detection of the actual binding potential of the SARS-CoV-2 proteins with their corresponding antigens. The measured binding interactions for RBD and NCP proteins with their corresponding antibodies under different conditions have been measured and analyzed. Based on these observations, a "hump or spike" in light intensity is observed when a specific molecular interaction takes place between two proteins. The optical responses could further be analyzed using the principle component analysis technique to enhance and allows precise detection of the specific target in a multi-protein mixture.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN40,

title = {A purine loop and the primer binding site are critical for the selective encapsidation of mouse mammary tumor virus genomic RNA by Pr77Gag},

author = {A. Chameettachal and V. Vivet-Boudou and F. N. N. Pitchai and V. N. Pillai and L. M. Ali and A. Krishnan and S. Bernacchi and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1093/nar/gkab223},

issn = {0305-1048 (Print) 0305-1048},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Nucleic Acids Res},

volume = {49},

number = {8},

pages = {4668-4688},

abstract = {Retroviral RNA genome (gRNA) harbors cis-acting sequences that facilitate its specific packaging from a pool of other viral and cellular RNAs by binding with high-affinity to the viral Gag protein during virus assembly. However, the molecular intricacies involved during selective gRNA packaging are poorly understood. Binding and footprinting assays on mouse mammary tumor virus (MMTV) gRNA with purified Pr77Gag along with in cell gRNA packaging study identified two Pr77Gag binding sites constituting critical, non-redundant packaging signals. These included: a purine loop in a bifurcated stem-loop containing the gRNA dimerization initiation site, and the primer binding site (PBS). Despite these sites being present on both unspliced and spliced RNAs, Pr77Gag specifically bound to unspliced RNA, since only that could adopt the native bifurcated stem-loop structure containing looped purines. These results map minimum structural elements required to initiate MMTV gRNA packaging, distinguishing features that are conserved amongst divergent retroviruses from those perhaps unique to MMTV. Unlike purine-rich motifs frequently associated with packaging signals, direct involvement of PBS in gRNA packaging has not been documented in retroviruses. These results enhance our understanding of retroviral gRNA packaging/assembly, making it not only a target for novel therapeutic interventions, but also development of safer gene therapy vectors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN92,

title = {Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula},

author = {S. F. Mouftah and T. Pál and P. G. Higgins and A. Ghazawi and Y. Idaghdour and M. Alqahtani and A. S. Omrani and T. A. Rizvi and Á Sonnevend},

doi = {10.1007/s10096-021-04384-2},

issn = {0934-9723},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Eur J Clin Microbiol Infect Dis},

abstract = {To understand the reasons of successful spread of carbapenem-resistant Klebsiella pneumoniae ST14 (CRKP-ST14) in countries of the Arabian Peninsula, the resistome, capsular locus, carbapenemase carrying plasmid types, and core genome of isolates from the region were compared to global isolates. Thirty-nine CRKP-ST14 strains isolated from 13 hospitals in the United Arab Emirates, Bahrain, and Saudi Arabia were selected for whole genome sequencing on Illumina MiSeq platform based on the variety of carbapenemase genes carried and plasmids bearing these genes. Their resistome, capsular locus, and core genome MLST were compared to 173 CRKP-ST14 genomes available in public databases. The selected 39 CRKP-ST14 produced either NDM-1, OXA-48, OXA-162, OXA-232, KPC-2, or co-produced NDM-1 and an OXA-48-like carbapenemase. cgMLST revealed three clusters: 16 isolates from five UAE cities (C1), 11 isolates from three UAE cities and Bahrain (C2), and 5 isolates from Saudi Arabia (C3), respectively, and seven singletons. Resistance gene profile, carbapenemase genes, and their plasmid types were variable in both C1 and C2 clusters. The majority of CRKP-ST14 had KL2, but members of the C2 cluster and two further singletons possessed KL64 capsular locus. Based on cgMLST comparison of regional and global isolates, CRKP-ST14 with KL64 from four continents formed a distinct cluster, suggesting a recent emergence and spread of this variant. Our findings confirmed clonal transmission coupled with likely horizontal gene transfer in carbapenem-resistant Klebsiella pneumoniae ST14. Dissemination of this genetically flexible, highly resistant clone warrants further monitoring.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN38,

title = {A Stretch of Unpaired Purines in the Leader Region of Simian Immunodeficiency Virus (SIV) Genomic RNA is Critical for its Packaging into Virions},

author = {V. N. Pillai and L. M. Ali and S. G. Prabhu and A. Krishnan and A. Chameettachal and F. N. N. Pitchai and F. Mustafa and T. A. Rizvi},

doi = {10.1016/j.jmb.2021.167293},

issn = {0022-2836},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Mol Biol},

volume = {433},

number = {23},

pages = {167293},

abstract = {Simian immunodeficiency virus (SIV) is an important lentivirus used as a non-human primate model to study HIV replication, and pathogenesis of human AIDS, as well as a potential vector for human gene therapy. This study investigated the role of single-stranded purines (ssPurines) as potential genomic RNA (gRNA) packaging determinants in SIV replication. Similar ssPurines have been implicated as important motifs for gRNA packaging in many retroviruses like, HIV-1, MPMV, and MMTV by serving as Gag binding sites during virion assembly. In examining the secondary structure of the SIV 5' leader region, as recently deduced using SHAPE methodology, we identified four specific stretches of ssPurines (I-IV) in the region that harbors major packaging determinants of SIV. The significance of these ssPurine motifs were investigated by mutational analysis coupled with a biologically relevant single round of replication assay. These analyses revealed that while ssPurine II was essential, the others (ssPurines I, III, & IV) did not significantly contribute to SIV gRNA packaging. Any mutation in the ssPurine II, such as its deletion or substitution, or other mutations that caused base pairing of ssPurine II loop resulted in near abrogation of RNA packaging, further substantiating the crucial role of ssPurine II and its looped conformation in SIV gRNA packaging. Structure prediction analysis of these mutants further corroborated the biological results and further revealed that the unpaired nature of ssPurine II is critical for its function during SIV RNA packaging perhaps by enabling it to function as a specific binding site for SIV Gag.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN19,

title = {Identification of Pr78(Gag) Binding Sites on the Mason-Pfizer Monkey Virus Genomic RNA Packaging Determinants},

author = {F. N. N. Pitchai and A. Chameettachal and V. Vivet-Boudou and L. M. Ali and V. N. Pillai and A. Krishnan and S. Bernacchi and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1016/j.jmb.2021.166923},

issn = {0022-2836},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Mol Biol},

volume = {433},

number = {10},

pages = {166923},

abstract = {How retroviral Gag proteins recognize the packaging signals (Psi) on their genomic RNA (gRNA) is a key question that we addressed here using Mason-Pfizer monkey virus (MPMV) as a model system by combining band-shift assays and footprinting experiments. Our data show that Pr78(Gag) selects gRNA against spliced viral RNA by simultaneously binding to two single stranded loops on the MPMV Psi RNA: (1) a large purine loop (ssPurines), and (2) a loop which partially overlaps with a mostly base-paired purine repeat (bpPurines) and extends into a GU-rich binding motif. Importantly, this second Gag binding site is located immediately downstream of the major splice donor (mSD) and is thus absent from the spliced viral RNAs. Identifying elements crucial for MPMV gRNA packaging should help in understanding not only the mechanism of virion assembly by retroviruses, but also facilitate construction of safer retroviral vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN28,

title = {Simultaneous and rapid quantification of microalga biomolecule content using electrochemical impedance spectroscopy},

author = {M. Al Ahmad and S. Raji and F. Mustafa and T. A. Rizvi and S. Al-Zuhair},

doi = {10.1002/btpr.3037},

issn = {1520-6033},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Biotechnol Prog},

volume = {36},

number = {6},

pages = {e3037},

abstract = {Lipids, proteins, and carbohydrates are the major constituents found in microalga cells, in varying proportions, and these biomolecules find applications in different industries. During microalga cultivation, to efficiently manipulate, control, and optimize the productivity of a specific compound for a specific application, real-time monitoring of these three cell components is essential. In this study, a method using measurement of electrical capacitance was developed to simultaneously determine the lipid, protein, and carbohydrate content of microalga cells without the requirement for any pre-processing steps. The marine microalga Nannochloropsis oculata was cultivated under nitrogen starvation conditions to induce lipid accumulation over a period of 22 days. The correlation between the electrical capacitance of the microalga culture and the intracellular biomolecule content (determined by standard techniques) was investigated, enabling subsequent deduction of microalga intracellular content from electrical capacitance of the culture. The accuracy and precision of the technique were proven by validating an independent sample. The main advantage of the proposed technique is its capability of quantifying microalga composition within a few minutes, significantly faster than currently available conventional techniques.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN36,

title = {Role of Purine-Rich Regions in Mason-Pfizer Monkey Virus (MPMV) Genomic RNA Packaging and Propagation},

author = {L. M. Ali and F. N. N. Pitchai and V. Vivet-Boudou and A. Chameettachal and A. Jabeen and V. N. Pillai and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.3389/fmicb.2020.595410},

issn = {1664-302X (Print) 1664-302x},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Front Microbiol},

volume = {11},

pages = {595410},

abstract = {A distinguishing feature of the Mason-Pfizer monkey virus (MPMV) packaging signal RNA secondary structure is a single-stranded purine-rich sequence (ssPurines) in close vicinity to a palindromic stem loop (Pal SL) that functions as MPMV dimerization initiation site (DIS). However, unlike other retroviruses, MPMV contains a partially base-paired repeat sequence of ssPurines (bpPurines) in the adjacent region. Both purine-rich sequences have earlier been proposed to act as potentially redundant Gag binding sites to initiate the process of MPMV genomic RNA (gRNA) packaging. The objective of this study was to investigate the biological significance of ssPurines and bpPurines in MPMV gRNA packaging by systematic mutational and biochemical probing analyses. Deletion of either ssPurines or bpPurines individually had no significant effect on MPMV gRNA packaging, but it was severely compromised when both sequences were deleted simultaneously. Selective 2' hydroxyl acylation analyzed by primer extension (SHAPE) analysis of the mutant RNAs revealed only mild effects on structure by deletion of either ssPurines or bpPurines, while the structure was dramatically affected by the two simultaneous deletions. This suggests that ssPurines and bpPurines play a redundant role in MPMV gRNA packaging, probably as Gag binding sites to facilitate gRNA capture and encapsidation. Interestingly, the deletion of bpPurines revealed an additional severe defect on RNA propagation that was independent of the presence or absence of ssPurines or the gRNA structure of the region. These findings further suggest that the bpPurines play an additional role in the early steps of MPMV replication cycle that is yet to be identified.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN22,

title = {Electrical detection of blood cells in urine},

author = {N. Nasir and S. Raji and F. Mustafa and T. A. Rizvi and Z. Al Natour and A. Hilal-Alnaqbi and M. Al Ahmad},

doi = {10.1016/j.heliyon.2019.e03102},

issn = {2405-8440 (Print) 2405-8440},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Heliyon},

volume = {6},

number = {1},

pages = {e03102},

abstract = {Available methods for detecting blood in the urine (hematuria) can be problematic since results can be influenced by many factors in patients and in the lab settings, resulting in false positive or false negative results. This necessitates the development of new, accurate and easy-access methods that save time and effort. This study demonstrates a label-free and accurate method for detecting the presence of red and white blood cells (RBCs and WBCs) in urine by measuring the changes in the dielectric properties of urine upon increasing concentrations of both cell types. The current method could detect changes in the electrical properties of fresh urine over a short time interval, making this method suitable for detecting changes that cannot be recognized by conventional methods. Correcting for these changes enabled the detection of a minimum cell concentration of 10(2) RBCs per ml which is not possible by conventional methods used in the labs except for the semi-quantitative method that can detect 50 RBCs per ml, but it is a lengthy and involved procedure, not suitable for high volume labs. This ability to detect very small amount of both types of cells makes the proposed technique an attractive tool for detecting hematuria, the presence of which is indicative of problems in the excretory system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN81,

title = {In vitro efficacy of ceftazidime-avibactam, aztreonam-avibactam and other rescue antibiotics against carbapenem-resistant Enterobacterales from the Arabian Peninsula},

author = {Á Sonnevend and A. Ghazawi and D. Darwish and G. Barathan and R. Hashmey and T. Ashraf and T. A. Rizvi and T. Pál},

doi = {10.1016/j.ijid.2020.07.050},

issn = {1201-9712},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Int J Infect Dis},

volume = {99},

pages = {253-259},

abstract = {OBJECTIVES: Our aim was to assess the susceptibility of carbapenem-resistant Enterobacterales (CRE) from the Arabian Peninsula to a broad spectrum of antibiotics, including fosfomycin, ceftazidime-avibactam, and aztreonam-avibactam. METHODS: 1192 non-repeat CRE isolated in 2009-2017 from 33 hospitals in five countries of the Arabian Peninsula were tested. The minimum inhibitory concentration of 14 antibiotics was determined. Carbapenemase and 16S methylase genes were detected by PCR. Clonality was assessed by PFGE. RESULTS: The highest rate of susceptibility was detected to aztreonam-avibactam (95.5%) followed by colistin (79.8%), fosfomycin (71.8%) and tigecycline (59.9%). Isolates co-producing two carbapenemases (12.4%) were the least susceptible. Aminoglycoside susceptibility was affected by the frequent production of a 16S methylase. Susceptibility to ceftazidime-avibactam was impacted by the high rate of metallo-beta-lactamase producers (46.3%), while aztreonam-avibactam resistance occurred mostly in clonally unrelated, carbapenemase non-producing Escherichia coli. CONCLUSION: Of the currently available drugs: colistin, tigecycline, and ceftazidime-avibactam co-administered with aztreonam appear to be the most effective to treat CRE infections. However, the presence of non-clonal CRE isolates, in which avibactam does not lower the aztreonam MIC below the clinical breakpoint, is of notable concern. Based on the relatively high rate of fosfomycin susceptibility, it would be desirable to license parenteral fosfomycin in the region.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN41,

title = {The Large Action of Chlorpromazine: Translational and Transdisciplinary Considerations in the Face of COVID-19},

author = {E. Stip and T. A. Rizvi and F. Mustafa and S. Javaid and S. Aburuz and N. N. Ahmed and K. Abdel Aziz and D. Arnone and A. Subbarayan and F. Al Mugaddam and G. Khan},

doi = {10.3389/fphar.2020.577678},

issn = {1663-9812 (Print) 1663-9812},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Front Pharmacol},

volume = {11},

pages = {577678},

abstract = {Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome (SARS) in humans that is caused by SARS-associated coronavirus type 2 (SARS-CoV-2). In the context of COVID-19, several aspects of the relations between psychiatry and the pandemic due to the coronavirus have been described. Some drugs used as antiviral medication have neuropsychiatric side effects, and conversely some psychotropic drugs have antiviral properties. Chlorpromazine (CPZ, Largactil(®)) is a well-established antipsychotic medication that has recently been proposed to have antiviral activity against SARS-CoV-2. This review aims to 1) inform health care professionals and scientists about the history of CPZ use in psychiatry and its potential anti- SARS-CoV-2 activities 2) inform psychiatrists about its potential anti-SARS-CoV-2 activities, and 3) propose a research protocol for investigating the use of CPZ in the treatment of COVID-19 during the potential second wave. The history of CPZ's discovery and development is described in addition to the review of literature from published studies within the discipline of virology related to CPZ. The early stages of infection with coronavirus are critical events in the course of the viral cycle. In particular, viral entry is the first step in the interaction between the virus and the cell that can initiate, maintain, and spread the infection. The possible mechanism of action of CPZ is related to virus cell entry via clathrin-mediated endocytosis. Therefore, CPZ could be useful to treat COVID-19 patients provided that its efficacy is evaluated in adequate and well-conducted clinical trials. Interestingly, clinical trials of very good quality are in progress. However, more information is still needed about the appropriate dosage regimen. In short, CPZ repositioning is defined as a new use beyond the field of psychiatry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN9,

title = {SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology, Vaccines, and Therapeutic Interventions},

author = {M. Uddin and F. Mustafa and T. A. Rizvi and T. Loney and H. A. Suwaidi and A. H. H. Al-Marzouqi and A. K. Eldin and N. Alsabeeha and T. E. Adrian and C. Stefanini and N. Nowotny and A. Alsheikh-Ali and A. C. Senok},

doi = {10.3390/v12050526},

issn = {1999-4915},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Viruses},

volume = {12},

number = {5},

abstract = {The COVID-19 pandemic is due to infection caused by the novel SARS-CoV-2 virus that impacts the lower respiratory tract. The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19 which is associated with severe pneumonia, acute respiratory distress, and fatality. To address this global crisis, up-to-date information on viral genomics and transcriptomics is crucial for understanding the origins and global dispersion of the virus, providing insights into viral pathogenicity, transmission, and epidemiology, and enabling strategies for therapeutic interventions, drug discovery, and vaccine development. Therefore, this review provides a comprehensive overview of COVID-19 epidemiology, genomic etiology, findings from recent transcriptomic map analysis, viral-human protein interactions, molecular diagnostics, and the current status of vaccine and novel therapeutic intervention development. Moreover, we provide an extensive list of resources that will help the scientific community access numerous types of databases related to SARS-CoV-2 OMICs and approaches to therapeutics related to COVID-19 treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN53,

title = {Stabilizing role of structural elements within the 5´ Untranslated Region (UTR) and gag sequences in Mason-Pfizer monkey virus (MPMV) genomic RNA packaging},

author = {R. M. Kalloush and V. Vivet-Boudou and L. M. Ali and V. N. Pillai and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1080/15476286.2019.1572424},

issn = {1547-6286 (Print) 1547-6286},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {RNA Biol},

volume = {16},

number = {5},

pages = {612-625},

abstract = {The Mason-Pfizer monkey virus (MPMV) genomic RNA (gRNA) packaging signal is a highly-structured element with several stem-loops held together by two phylogenetically conserved long-range interactions (LRIs) between U5 and gag complementary sequences. These LRIs play a critical role in maintaining the structure of the 5´ end of the MPMV gRNA. Thus, one could hypothesize that the overall RNA secondary structure of this region is further architecturally held together by three other stem loops (SL3, Gag SL1, and Gag SL2) comprising of sequences from the distal parts of the 5´untranslated region (5' UTR) to ~ 120 nucleotides into gag, excluding gag sequences involved in forming the U5-Gag LRIs. To provide functional evidence for the biological significance of these stem loops during gRNA encapsidation, these structural motifs were mutated and their effects on MPMV RNA packaging and propagation were tested in a single round trans-complementation assay. The mutant RNA structures were further studied by high throughput SHAPE (hSHAPE) assay. Our results reveal that sequences involved in forming these three stem loops do not play crucial roles at an individual level during MPMV gRNA packaging or propagation. Further structure-function analysis indicates that the U5-Gag LRIs have a more important architectural role in stabilizing the higher order structure of the 5´ UTR than the three stem loops which have a more secondary and perhaps indirect role in stabilizing the overall RNA secondary structure of the region. Our work provides a better understanding of the molecular interactions that take place during MPMV gRNA packaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN32,

title = {A cis-Acting Element Downstream of the Mouse Mammary Tumor Virus Major Splice Donor Critical for RNA Elongation and Stability},

author = {S. Akhlaq and N. G. Panicker and P. S. Philip and L. M. Ali and J. P. Dudley and T. A. Rizvi and F. Mustafa},

doi = {10.1016/j.jmb.2018.08.025},

issn = {0022-2836 (Print) 0022-2836},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {J Mol Biol},

volume = {430},

number = {21},

pages = {4307-4324},

abstract = {BACKGROUND: The mouse mammary tumor virus (MMTV) encodes a functional signal peptide, a cleavage product of envelope and Rem proteins. Signal peptide interacts with a 3' cis-acting RNA element, the Rem-responsive element (RmRE), to facilitate expression of both unspliced genomic (gRNA) and spliced mRNAs. An additional RmRE has been proposed at the 5' end of the genome, facilitating nuclear export of the unspliced gRNA, whereas the 3' RmRE could facilitate translation of all other mRNAs, including gRNA. RESULTS: To address this hypothesis, a series of mutations were introduced into a 24-nt region found exclusively in the unspliced gRNA. Mutant clones using MMTV or human cytomegalovirus promoters were tested in both transient and stable transfections to determine their effect on gRNA nuclear export, stability, and translation. Nuclear export of the gRNA was affected only in a small mutant subset in stably transfected Jurkat T cells. Quantitative real-time RT-PCR of actinomycin D-treated cells expressing MMTV revealed that multiple mutants were severely compromised for RNA expression and stability. Both genomic and spliced nuclear RNAs were reduced, leading to abrogation of Gag and Env protein expressed from unspliced and spliced mRNAs, respectively. RT-PCRs with multiple primer pairs indicated failure to elongate genomic MMTV transcripts beyond ~500 nt compared to the wild type in a cell line-dependent manner. CONCLUSIONS: MMTV contains a novel cis-acting element downstream of the major splice donor critical for facilitating MMTV gRNA elongation and stability. Presence of a mirror repeat within the element may represent important viral/host factor binding site(s) within MMTV gRNA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN88,

title = {Biochemical and Functional Characterization of Mouse Mammary Tumor Virus Full-Length Pr77(Gag) Expressed in Prokaryotic and Eukaryotic Cells},

author = {A. Chameettachal and V. N. Pillai and L. M. Ali and F. N. N. Pitchai and M. T. Ardah and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.3390/v10060334},

issn = {1999-4915},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {Viruses},

volume = {10},

number = {6},

abstract = {The mouse mammary tumor virus (MMTV) Pr77(Gag) polypeptide is an essential retroviral structural protein without which infectious viral particles cannot be formed. This process requires specific recognition and packaging of dimerized genomic RNA (gRNA) by Gag during virus assembly. Most of the previous work on retroviral assembly has used either the nucleocapsid portion of Gag, or other truncated Gag derivatives—not the natural substrate for virus assembly. In order to understand the molecular mechanism of MMTV gRNA packaging process, we expressed and purified full-length recombinant Pr77(Gag)-His₆-tag fusion protein from soluble fractions of bacterial cultures. We show that the purified Pr77(Gag)-His₆-tag protein retained the ability to assemble virus-like particles (VLPs) in vitro with morphologically similar immature intracellular particles. The recombinant proteins (with and without His₆-tag) could both be expressed in prokaryotic and eukaryotic cells and had the ability to form VLPs in vivo. Most importantly, the recombinant Pr77(Gag)-His₆-tag fusion proteins capable of making VLPs in eukaryotic cells were competent for packaging sub-genomic MMTV RNAs. The successful expression and purification of a biologically active, full-length MMTV Pr77(Gag) should lay down the foundation towards performing RNA–protein interaction(s), especially for structure-function studies and towards understanding molecular intricacies during MMTV gRNA packaging and assembly processes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN90,

title = {The bifurcated stem loop 4 (SL4) is crucial for efficient packaging of mouse mammary tumor virus (MMTV) genomic RNA},

author = {F. Mustafa and V. Vivet-Boudou and A. Jabeen and L. M. Ali and R. M. Kalloush and R. Marquet and T. A. Rizvi},

doi = {10.1080/15476286.2018.1486661},

issn = {1547-6286 (Print) 1547-6286},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {RNA Biol},

volume = {15},

number = {8},

pages = {1047-1059},

abstract = {Packaging the mouse mammary tumor virus (MMTV) genomic RNA (gRNA) requires the entire 5' untranslated region (UTR) in conjunction with the first 120 nucleotides of the gag gene. This region includes several palindromic (pal) sequence(s) and stable stem loops (SLs). Among these, stem loop 4 (SL4) adopts a bifurcated structure consisting of three stems, two apical loops, and an internal loop. Pal II, located in one of the apical loops, mediates gRNA dimerization, a process intricately linked to packaging. We thus hypothesized that the bifurcated SL4 structure could constitute the major gRNA packaging determinant. To test this hypothesis, the two apical loops and the flanking sequences forming the bifurcated SL4 were individually mutated. These mutations all had deleterious effects on gRNA packaging and propagation. Next, single and compensatory mutants were designed to destabilize then recreate the bifurcated SL4 structure. A structure-function analysis using bioinformatics predictions and RNA chemical probing revealed that mutations that led to the loss of the SL4 bifurcated structure abrogated RNA packaging and propagation, while compensatory mutations that recreated the native SL4 structure restored RNA packaging and propagation to wild type levels. Altogether, our results demonstrate that SL4 constitutes the principal packaging determinant of MMTV gRNA. Our findings further suggest that SL4 acts as a structural switch that can not only differentiate between RNA for translation versus packaging/dimerization, but its location also allows differentiation between spliced and unspliced RNAs during gRNA encapsidation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN51,

title = {Expression, purification, and characterization of biologically active full-length Mason-Pfizer monkey virus (MPMV) Pr78(Gag)},

author = {F. N. N. Pitchai and L. Ali and V. N. Pillai and A. Chameettachal and S. S. Ashraf and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1038/s41598-018-30142-0},

issn = {2045-2322},

year  = {2018},

date = {2018-01-01},

urldate = {2018-01-01},

journal = {Sci Rep},

volume = {8},

number = {1},

pages = {11793},

abstract = {MPMV precursor polypeptide Pr78(Gag) orchestrates assembly and packaging of genomic RNA (gRNA) into virus particles. Therefore, we have expressed recombinant full-length Pr78(Gag) either with or without His(6)-tag in bacterial as well as eukaryotic cultures and purified the recombinant protein from soluble fractions of the bacterial cultures. The recombinant Pr78(Gag) protein has the intrinsic ability to assemble in vitro to form virus like particles (VLPs). Consistent with this observation, the recombinant protein could form VLPs in both prokaryotes and eukaryotes. VLPs formed in eukaryotic cells by recombinant Pr78(Gag) with or without His(6)-tag can encapsidate MPMV transfer vector RNA, suggesting that the inclusion of the His(6)-tag to the full-length Pr78(Gag) did not interfere with its expression or biological function. This study demonstrates the expression and purification of a biologically active, recombinant Pr78(Gag), which should pave the way to study RNA-protein interactions involved in the MPMV gRNA packaging process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN18,

title = {Electrical characterization of DNA supported on nitrocellulose membranes},

author = {M. A. Ahmad and R. M. Milhem and N. G. Panicker and T. A. Rizvi and F. Mustafa},

doi = {10.1038/srep29089},

issn = {2045-2322},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Sci Rep},

volume = {6},

pages = {29089},

abstract = {Integrated DNA-based nanoscale electronic devices will enable the continued realization of Moore's Law at the level of functional devices and systems. In this work, the electrical characterization of single and complementary base paired DNA has been directly measured and investigated via the use of nitrocellulose membranes. A radio frequency DAKS-3.5 was used to measure the reflection coefficients of different DNA solutions dotted onto nitrocellulose membranes. Each DNA solution was exposed to a radio frequency signal with a power of 10 dBm and with a sweep from 200 MHz up to 13.6 GHz. The conducted measurements show some distinctions between the homomeric and complementary bases due to their different electrical polarization. As revealed from the measurements conducted, with the addition of DNA oligonucleotides, the measured capacitance increased when compared with buffer medium alone. The DNA molecules could be modeled as dielectric material that can hold electrical charges. Furthermore, the complementary paired DNA molecule-based inks solutions had a higher capacitance value compared with single DNA molecules (A, C, G and T) solutions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN101,

title = {Electrical detection and quantification of single and mixed DNA nucleotides in suspension},

author = {M. A. Ahmad and N. G. Panicker and T. A. Rizvi and F. Mustafa},

doi = {10.1038/srep34016},

issn = {2045-2322},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Sci Rep},

volume = {6},

pages = {34016},

abstract = {High speed sequential identification of the building blocks of DNA, (deoxyribonucleotides or nucleotides for short) without labeling or processing in long reads of DNA is the need of the hour. This can be accomplished through exploiting their unique electrical properties. In this study, the four different types of nucleotides that constitute a DNA molecule were suspended in a buffer followed by performing several types of electrical measurements. These electrical parameters were then used to quantify the suspended DNA nucleotides. Thus, we present a purely electrical counting scheme based on the semiconductor theory that allows one to determine the number of nucleotides in a solution by measuring their capacitance-voltage dependency. The nucleotide count was observed to be similar to the multiplication of the corresponding dopant concentration and debye volume after de-embedding the buffer contribution. The presented approach allows for a fast and label-free quantification of single and mixed nucleotides in a solution.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN15,

title = {Cross- and Co-Packaging of Retroviral RNAs and Their Consequences},

author = {L. M. Ali and T. A. Rizvi and F. Mustafa},

doi = {10.3390/v8100276},

issn = {1999-4915},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Viruses},

volume = {8},

number = {10},

abstract = {Retroviruses belong to the family Retroviridae and are ribonucleoprotein (RNP) particles that contain a dimeric RNA genome. Retroviral particle assembly is a complex process, and how the virus is able to recognize and specifically capture the genomic RNA (gRNA) among millions of other cellular and spliced retroviral RNAs has been the subject of extensive investigation over the last two decades. The specificity towards RNA packaging requires higher order interactions of the retroviral gRNA with the structural Gag proteins. Moreover, several retroviruses have been shown to have the ability to cross-/co-package gRNA from other retroviruses, despite little sequence homology. This review will compare the determinants of gRNA encapsidation among different retroviruses, followed by an examination of our current understanding of the interaction between diverse viral genomes and heterologous proteins, leading to their cross-/co-packaging. Retroviruses are well-known serious animal and human pathogens, and such a cross-/co-packaging phenomenon could result in the generation of novel viral variants with unknown pathogenic potential. At the same time, however, an enhanced understanding of the molecular mechanisms involved in these specific interactions makes retroviruses an attractive target for anti-viral drugs, vaccines, and vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN77,

title = {Packaging of Mason-Pfizer monkey virus (MPMV) genomic RNA depends upon conserved long-range interactions (LRIs) between U5 and gag sequences},

author = {R. M. Kalloush and V. Vivet-Boudou and L. M. Ali and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1261/rna.055731.115},

issn = {1355-8382 (Print) 1355-8382},

year  = {2016},

date = {2016-01-01},

urldate = {2016-01-01},

journal = {Rna},

volume = {22},

number = {6},

pages = {905-19},

abstract = {MPMV has great potential for development as a vector for gene therapy. In this respect, precisely defining the sequences and structural motifs that are important for dimerization and packaging of its genomic RNA (gRNA) are of utmost importance. A distinguishing feature of the MPMV gRNA packaging signal is two phylogenetically conserved long-range interactions (LRIs) between U5 and gag complementary sequences, LRI-I and LRI-II. To test their biological significance in the MPMV life cycle, we introduced mutations into these structural motifs and tested their effects on MPMV gRNA packaging and propagation. Furthermore, we probed the structure of key mutants using SHAPE (selective 2'hydroxyl acylation analyzed by primer extension). Disrupting base-pairing of the LRIs affected gRNA packaging and propagation, demonstrating their significance to the MPMV life cycle. A double mutant restoring a heterologous LRI-I was fully functional, whereas a similar LRI-II mutant failed to restore gRNA packaging and propagation. These results demonstrate that while LRI-I acts at the structural level, maintaining base-pairing is not sufficient for LRI-II function. In addition, in vitro RNA dimerization assays indicated that the loss of RNA packaging in LRI mutants could not be attributed to the defects in dimerization. Our findings suggest that U5-gag LRIs play an important architectural role in maintaining the structure of the 5' region of the MPMV gRNA, expanding the crucial role of LRIs to the nonlentiviral group of retroviruses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN21,

title = {Label-free capacitance-based identification of viruses},

author = {M. Al Ahmad and F. Mustafa and L. M. Ali and J. V. Karakkat and T. A. Rizvi},

doi = {10.1038/srep09809},

issn = {2045-2322},

year  = {2015},

date = {2015-01-01},

urldate = {2015-01-01},

journal = {Sci Rep},

volume = {5},

pages = {9809},

abstract = {This study was undertaken to quantitate a single virus suspension in culture medium without any pre-processing. The electrical capacitance per virus particle was used to identify the kind of virus present by measuring the suspension (virus plus medium) capacitance, de-embedding the medium contribution, and dividing by the virus count. The proposed technique is based on finding the single virus effective dielectric constant which is directly related to the virus composition. This value was used to identify the virus type accordingly. Two types of viruses thus tested were further quantified by a biochemical technique to validate the results. Furthermore, non-organic nanoparticles with known concentration and capacitance per particle were identified using the proposed method. The selectivity of the method was demonstrated by performing electrical measurements on a third virus, revealing that the proposed technique is specific and sensitive enough to permit detection of a few hundred virus particles per milliliter within a few minutes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN117,

title = {Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells},

author = {M. Ali Khan and M. Kedhari Sundaram and A. Hamza and U. Quraishi and D. Gunasekera and L. Ramesh and P. Goala and U. Al Alami and M. Z. Ansari and T. A. Rizvi and C. Sharma and A. Hussain},

doi = {10.1155/2015/412149},

issn = {1741-427X (Print) 1741-427x},

year  = {2015},

date = {2015-01-01},

urldate = {2015-01-01},

journal = {Evid Based Complement Alternat Med},

volume = {2015},

pages = {412149},

abstract = {Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 µM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARβ, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN59,

title = {Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV)},

author = {S. J. Aktar and V. Vivet-Boudou and L. M. Ali and A. Jabeen and R. M. Kalloush and D. Richer and F. Mustafa and R. Marquet and T. A. Rizvi},

doi = {10.1186/s12977-014-0096-6},

issn = {1742-4690},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {Retrovirology},

volume = {11},

pages = {96},

abstract = {BACKGROUND: One of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral gRNA in the form of a non-covalent RNA dimer by the assembling virions. It is becoming increasingly clear that the process of dimerization is closely linked with gRNA packaging, and in some retroviruses, the latter depends on the former. Earlier mutational analysis of the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants comprise sequences both within the 5' untranslated region (5' UTR) and the beginning of gag. RESULTS: The RNA secondary structure of MMTV gRNA packaging sequences was elucidated employing selective 2'hydroxyl acylation analyzed by primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long-range interaction (U5/Gag LRI), not predicted by minimum free-energy structure predictions that potentially stabilizes the global structure of this region. Structure conservation along with base-pair covariations between different strains of MMTV further supported the SHAPE-validated model. The 5' region of the MMTV gRNA contains multiple palindromic (pal) sequences that could initiate intermolecular interaction during RNA dimerization. In vitro RNA dimerization, SHAPE analysis, and structure prediction approaches on a series of pal mutants revealed that MMTV RNA utilizes a palindromic point of contact to initiate intermolecular interactions between two gRNAs, leading to dimerization. This contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization initiation site (DIS). Further analyses of these pal mutants employing in vivo genetic approaches indicate that pal II, as well as pal sequences located in the primer binding site (PBS) are both required for efficient MMTV gRNA packaging. CONCLUSIONS: Employing structural prediction, biochemical, and genetic approaches, we show that pal II functions as a primary point of contact between two MMTV RNAs, leading to gRNA dimerization and its subsequent encapsidation into the assembling virus particles. The results presented here enhance our understanding of the MMTV gRNA dimerization and packaging processes and the role of structural motifs with respect to RNA-RNA and possibly RNA-protein interactions that might be taking place during MMTV life cycle.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN24,

title = {Virus detection and quantification using electrical parameters},

author = {M. Al Ahmad and F. Mustafa and L. M. Ali and T. A. Rizvi},

doi = {10.1038/srep06831},

issn = {2045-2322},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {Sci Rep},

volume = {4},

pages = {6831},

abstract = {Here we identify and quantitate two similar viruses, human and feline immunodeficiency viruses (HIV and FIV), suspended in a liquid medium without labeling, using a semiconductor technique. The virus count was estimated by calculating the impurities inside a defined volume by observing the change in electrical parameters. Empirically, the virus count was similar to the absolute value of the ratio of the change of the virus suspension dopant concentration relative to the mock dopant over the change in virus suspension Debye volume relative to mock Debye volume. The virus type was identified by constructing a concentration-mobility relationship which is unique for each kind of virus, allowing for a fast (within minutes) and label-free virus quantification and identification. For validation, the HIV and FIV virus preparations were further quantified by a biochemical technique and the results obtained by both approaches corroborated well. We further demonstrate that the electrical technique could be applied to accurately measure and characterize silica nanoparticles that resemble the virus particles in size. Based on these results, we anticipate our present approach to be a starting point towards establishing the foundation for label-free electrical-based identification and quantification of an unlimited number of viruses and other nano-sized particles.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN109,

title = {Ethanolic Neem (Azadirachta indica) Leaf Extract Prevents Growth of MCF-7 and HeLa Cells and Potentiates the Therapeutic Index of Cisplatin},

author = {C. Sharma and A. J. Vas and P. Goala and T. M. Gheewala and T. A. Rizvi and A. Hussain},

doi = {10.1155/2014/321754},

issn = {1687-8450 (Print) 1687-8450},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {J Oncol},

volume = {2014},

pages = {321754},

abstract = {The present study was designed to gain insight into the antiproliferative activity of ethanolic neem leaves extract (ENLE) alone or in combination with cisplatin by cell viability assay on human breast (MCF-7) and cervical (HeLa) cancer cells. Nuclear morphological examination and cell cycle analysis were performed to determine the mode of cell death. Further, to identify its molecular targets, the expression of genes involved in apoptosis, cell cycle progression, and drug metabolism was analyzed by RT-PCR. Treatment of MCF-7, HeLa, and normal cells with ENLE differentially suppressed the growth of cancer cells in a dose- and time-dependent manner through apoptosis. Additionally, lower dose combinations of ENLE with cisplatin resulted in synergistic growth inhibition of these cells compared to the individual drugs (combination index <1). ENLE significantly modulated the expression of bax, cyclin D1, and cytochrome P450 monooxygenases (CYP 1A1 and CYP 1A2) in a time-dependent manner in these cells. Conclusively, these results emphasize the chemopreventive ability of neem alone or in combination with chemotherapeutic treatment to reduce the cytotoxic effects on normal cells, while potentiating their efficacy at lower doses. Thus, neem may be a prospective therapeutic agent to combat gynecological cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN80,

title = {SHAPE analysis of the 5' end of the Mason-Pfizer monkey virus (MPMV) genomic RNA reveals structural elements required for genome dimerization},

author = {S. J. Aktar and A. Jabeen and L. M. Ali and V. Vivet-Boudou and R. Marquet and T. A. Rizvi},

doi = {10.1261/rna.040931.113},

issn = {1355-8382 (Print) 1355-8382},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {Rna},

volume = {19},

number = {12},

pages = {1648-58},

abstract = {Earlier genetic and structural prediction analyses revealed that the packaging determinants of Mason Pfizer monkey virus (MPMV) include two discontinuous core regions at the 5' end of its genomic RNA. RNA secondary structure predictions suggested that these packaging determinants fold into several stem-loops (SLs). To experimentally validate this structural model, we employed selective 2' hydroxyl acylation analyzed by primer extension (SHAPE), which examines the flexibility of the RNA backbone at each nucleotide position. Our SHAPE data validated several predicted structural motifs, including U5/Gag long-range interactions (LRIs), a stretch of single-stranded purine (ssPurine)-rich region, and a distinctive G-C-rich palindromic (pal) SL. Minimum free-energy structure predictions, phylogenetic, and in silico modeling analyses of different MPMV strains revealed that the U5 and gag sequences involved in the LRIs differ minimally within strains and maintain a very high degree of complementarity. Since the pal SL forms a helix loop containing a canonical "GC" dyad, it may act as a RNA dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Analyses of wild-type and pal mutant RNAs revealed that disruption of pal sequence strongly affected RNA dimerization. However, when in vitro transcribed trans-complementary pal mutants were incubated together showed RNA dimerization was restored authenticating that the pal loop (5'-CGGCCG-3') functions as DIS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN35,

title = {Bioenergetics of murine lungs infected with respiratory syncytial virus},

author = {A. R. Alsuwaidi and S. Benedict and J. Kochiyil and F. Mustafa and S. M. Hartwig and S. Almarzooqi and A. Albawardi and T. A. Rizvi and S. M. Varga and A. K. Souid},

doi = {10.1186/1743-422x-10-22},

issn = {1743-422x},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {Virol J},

volume = {10},

pages = {22},

abstract = {BACKGROUND: Cellular bioenergetics (cellular respiration and accompanying ATP synthesis) is a highly sensitive biomarker of tissue injury and may be altered following infection. The status of cellular mitochondrial O(2) consumption of the lung in pulmonary RSV infection is unknown. METHODS: In this study, lung fragments from RSV-infected BALB/c mice were evaluated for cellular O(2) consumption, ATP content and caspase activity. The disease was induced by intranasal inoculation with the RSV strain A2 and lung specimens were analyzed on days 2-15 after inoculation. A phosphorescence O(2) analyzer that measured dissolved O(2) concentration as a function of time was used to monitor respiration. The caspase-3 substrate analogue N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspases. RESULTS: O(2) concentration declined linearly with time when measured in a sealed vial containing lung fragment and glucose as a respiratory substrate, revealing its zero-order kinetics. O(2) consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Cellular respiration increased by 1.6-fold (p<0.010) and ATP content increased by 3-fold in the first week of RSV infection. Both parameters returned to levels found in uninfected lungs in the second week of RSV infection. Intracellular caspase activity in infected lungs was similar to uninfected lungs throughout the course of disease. CONCLUSIONS: Lung tissue bioenergetics is transiently enhanced in RSV infection. This energy burst, triggered by the virus or virus-induced inflammation, is an early biomarker of the disease and may be targeted for therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN62,

title = {Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition},

author = {C. E. Prada and E. Jousma and T. A. Rizvi and J. Wu and R. S. Dunn and D. A. Mayes and J. A. Cancelas and E. Dombi and M. O. Kim and B. L. West and G. Bollag and N. Ratner},

doi = {10.1007/s00401-012-1056-7},

issn = {0001-6322 (Print) 0001-6322},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {Acta Neuropathol},

volume = {125},

number = {1},

pages = {159-68},

abstract = {Neurofibromatosis type 1 (NF1) is a common genetic disease that predisposes 30-50 % of affected individuals to develop plexiform neurofibromas. We found that macrophage infiltration of both mouse and human neurofibromas correlates with disease progression. Macrophages accounted for almost half of neurofibroma cells, leading us to hypothesize that nerve macrophages are inflammatory effectors in neurofibroma development and/or growth. We tested the effects of PLX3397, a dual kit/fms kinase inhibitor that blocks macrophage infiltration, in the Dhh-Cre; Nf1(flox/flox) mouse model of GEM grade I neurofibroma. In mice aged 1-4 months, prior to development of nerve pathology and neurofibroma formation, PLX3397 did not impair tumor initiation and increased tumor volume compared to controls. However, in mice aged 7-9 months, after tumor establishment, a subset of mice demonstrating the largest reductions in macrophages after PLX3397 exhibited cell death and tumor volume regression. Macrophages are likely to provide an initial line of defense against developing tumors. Once tumors are established, they become tumor permissive. Macrophage depletion may result in impaired tumor maintenance and represent a therapeutic strategy for neurofibroma therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN54,

title = {Estrogenic activities of ten medicinal herbs from the Middle East},

author = {I. A. Saeed and L. Ali and A. Jabeen and M. Khasawneh and T. A. Rizvi and S. S. Ashraf},

doi = {10.1093/chromsci/bms101},

issn = {0021-9665},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {J Chromatogr Sci},

volume = {51},

number = {1},

pages = {33-9},

abstract = {Traditional medicinal plants have long been recognized as remedies and important sources of treatment for developing countries. In the present study, we report on a detailed study to quantify the presence of five known phytoestrogens in 10 widely used herbs used in the Middle East. Surprisingly some of these plants were almost devoid of tested phytoestrogens, whereas others were very rich in known phytoestrogens. For example, Hibiscus sabdariffa was found to be the richest in quercetin and daidzein, whereas Cyperus conglomeratus had the highest concentrations of kaempferol and genistein. On the other hand, Salvadora persica was almost devoid of the screened phytoestrogens. Ethanolic extracts were further tested for their proliferative activities in cell-culture using estrogen-responsive breast cancer cell lines (MCF-7) and were found to fall into three distinct groups based on their estrogenic activities. The most potent herbal extract (O. vulgare) was further fractionated and the fractions were analyzed again for phytoestrogenic content (using high-performance liquid chromatography) and proliferative activity. Our results indicate that the proliferative activities of some of the extracts and fractions are not completely attributable to the phytoestrogens screened, thus it is likely that some of these plants may have other (perhaps yet unknown) phytoestrogens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN130,

title = {Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitors of matrix metalloproteinase-1 expression},

author = {A. Hussain and G. Harish and S. A. Prabhu and J. Mohsin and M. A. Khan and T. A. Rizvi and C. Sharma},

doi = {10.1016/j.canep.2012.07.005},

issn = {1877-7821},

year  = {2012},

date = {2012-01-01},

urldate = {2012-01-01},

journal = {Cancer Epidemiol},

volume = {36},

number = {6},

pages = {e387-93},

abstract = {BACKGROUND: One of the most challenging stumbling blocks for the treatment of cancer is the ability of cancer cells to break the natural barriers and spread from its site of origin to non-adjacent regional and distant sites, accounting for high cancer mortality rates. Gamut experimental and epidemiological data advocate the use of pharmacological or nutritional interventions to inhibit or delay various stage(s) of cancer such as invasion and metastasis. Genistein, a promising chemopreventive agent, has gained considerable attention for its powerful anti-carcinogenic, anti-angiogenic and chemosensitizing activities. METHODS: In this study, the cytotoxic potential of genistein on HeLa cells by cell viability assay and the mode of cell death induced by genistein were determined by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Moreover, to establish its inhibitory effect on migration of HeLa cells, scratch wound assay was performed and these results were correlated with the expression of genes involved in invasion and migration (MMP-9 and TIMP-1) by RT-PCR. RESULTS: The exposure of HeLa cells to genistein resulted in significant dose- and time-dependent growth inhibition, which was found to be mediated by apoptosis and cell cycle arrest at G(2)/M phase. In addition, it induced migration-inhibition in a time-dependent manner by modulating the expression of MMP-9 and TIMP-1. CONCLUSION: Our results signify that genistein may be an effective anti-neoplastic agent to prevent cancer cell growth and invasion and metastasis. Therefore therapeutic strategies utilizing genistein could be developed to substantially reduce cancer morbidity and mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN58,

title = {NDM-2 carbapenemase-producing Acinetobacter baumannii in the United Arab Emirates},

author = {A. Ghazawi and A. Sonnevend and R. A. Bonnin and L. Poirel and P. Nordmann and R. Hashmey and T. A. Rizvi and B. Hamadeh M and T. Pál},

doi = {10.1111/j.1469-0691.2011.03726.x},

issn = {1198-743x},

year  = {2012},

date = {2012-01-01},

urldate = {2012-01-01},

journal = {Clin Microbiol Infect},

volume = {18},

number = {2},

pages = {E34-6},

abstract = {Screening 155 carbapenem non-susceptible Acinetobacter baumannii strains recovered in Abu Dhabi hospitals identified two metallo-ß-lactamase bla(NDM) gene-carrying isolates. They were isolated 4 months apart from the urine of a cancer patient previously treated in Egypt, Lebanon and in the United Arab Emirates. They were clonally related and carried the bla(NDM-2) gene recently identified in A. baumannii in Egypt and Israel. Sequences surrounding the bla(NDM-2) gene showed significant similarities with those associated with bla(NDM-1) in Enterobacteriaceae and A. baumannii. Repeated isolation of bla(NDM-2)-positive A. baumannii in the Middle East raises the possibility of the local emergence and spread of a unique clone.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN85,

title = {(-)-Epigallocatechin-3-gallate induces apoptosis and inhibits invasion and migration of human cervical cancer cells},

author = {C. Sharma and A. Nusri Qel and S. Begum and E. Javed and T. A. Rizvi and A. Hussain},

doi = {10.7314/apjcp.2012.13.9.4815},

issn = {1513-7368},

year  = {2012},

date = {2012-01-01},

urldate = {2012-01-01},

journal = {Asian Pac J Cancer Prev},

volume = {13},

number = {9},

pages = {4815-22},

abstract = {Invasion and metastasis are the major causes of cancer-related death. Pharmacological or therapeutic interventions such as chemoprevention of the progression stages of neoplastic development could result in substantial reduction in the incidence of cancer mortality. (-)-Epigallocatechin-3-gallate (EGCG), a promising chemopreventive agent, has attracted extensive interest for cancer therapy utilizing its antioxidant, anti- proliferative and inhibitory effects on angiogenesis and tumor cell invasion. In this study, we assessed the influence of EGCG on the proliferative potential of HeLa cells by cell viability assay and authenticated the results by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Further we analyzed the anti-invasive properties of EGCG by wound migration assay and gene expression of MMP-9 and TIMP-1 in HeLa cells. Our results indicated that EGCG induced growth inhibition of HeLa cells in a dose- and time- dependent manner. It was observed that cell death mediated by EGCG was through apoptosis. Interestingly, EGCG effectively inhibited invasion and migration of HeLa cells and modulated the expression of related genes (MMP-9 and TIMP-1) . These results indicate that EGCG may effectively suppress promotion and progression stages of cervical cancer development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN89,

title = {Sequences within both the 5' UTR and Gag are required for optimal in vivo packaging and propagation of mouse mammary tumor virus (MMTV) genomic RNA},

author = {F. Mustafa and D. Al Amri and F. Al Ali and N. Al Sari and S. Al Suwaidi and P. Jayanth and P. S. Philips and T. A. Rizvi},

doi = {10.1371/journal.pone.0047088},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

urldate = {2012-01-01},

journal = {PLoS One},

volume = {7},

number = {10},

pages = {e47088},

abstract = {BACKGROUND: This study mapped regions of genomic RNA (gRNA) important for packaging and propagation of mouse mammary tumor virus (MMTV). MMTV is a type B betaretrovirus which preassembles intracellularly, a phenomenon distinct from retroviruses that assemble the progeny virion at cell surface just before budding such as the type C human and feline immunodeficiency viruses (HIV and FIV). Studies of FIV and Mason-Pfizer monkey virus (MPMV), a type D betaretrovirus with similar intracellular virion assembly processes as MMTV, have shown that the 5' untranslated region (5' UTR) and 5' end of gag constitute important packaging determinants for gRNA. METHODOLOGY: Three series of MMTV transfer vectors containing incremental amounts of gag or 5' UTR sequences, or incremental amounts of 5' UTR in the presence of 400 nucleotides (nt) of gag were constructed to delineate the extent of 5' sequences that may be involved in MMTV gRNA packaging. Real time PCR measured the packaging efficiency of these vector RNAs into MMTV particles generated by co-transfection of MMTV Gag/Pol, vesicular stomatitis virus envelope glycoprotein (VSV-G Env), and individual transfer vectors into human 293T cells. Transfer vector RNA propagation was monitored by measuring transduction of target HeLaT4 cells following infection with viral particles containing a hygromycin resistance gene expression cassette on the packaged RNA. PRINCIPAL FINDINGS: MMTV requires the entire 5' UTR and a minimum of ~120 nucleotide (nt) at the 5' end of gag for not only efficient gRNA packaging but also propagation of MMTV-based transfer vector RNAs. Vector RNAs without the entire 5' UTR were defective for both efficient packaging and propagation into target cells. CONCLUSIONS/SIGNIFICANCE: These results reveal that the 5' end of MMTV genome is critical for both gRNA packaging and propagation, unlike the recently delineated FIV and MPMV packaging determinants that have been shown to be of bipartite nature.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN70,

title = {Reciprocal cross-packaging of primate lentiviral (HIV-1 and SIV) RNAs by heterologous non-lentiviral MPMV proteins},

author = {I. R. Al Shamsi and N. S. Al Dhaheri and P. S. Phillip and F. Mustafa and T. A. Rizvi},

doi = {10.1016/j.virusres.2010.09.018},

issn = {0168-1702},

year  = {2011},

date = {2011-01-01},

urldate = {2011-01-01},

journal = {Virus Res},

volume = {155},

number = {1},

pages = {352-7},

abstract = {Retroviral RNA packaging signal (ψ) allows the preferential packaging of genomic RNA into virus particles through its interaction with the nucleocapsid protein. The specificity of this interaction came into question when it was shown that primate retroviruses, such as HIV-1, could cross-package RNA from its simian cousin, SIV, and vice versa and that feline retrovirus, FIV could cross-package RNA from a distantly related primate retrovirus, MPMV. To study the generality of this phenomenon further, we determined whether there is a greater packaging restriction between the lentiviral class of retroviruses (HIV-1 and SIV) and a non-lentivirus, MPMV. Our results revealed that primate lentiviral RNAs can be cross-packaged by primate non-lentiviral particles reciprocally, but the cross-packaged RNAs could not be propagated by the heterologous particles. Packaging of RNA in the context of both retroviral vectors as well as non-retroviral RNA containing SIV, HIV, and MPMV packaging determinants by each others proteins further confirmed the specificity of cross-packaging conferred by the packaging sequences. These results reveal the promiscuous nature of retroviral packaging determinants and raise caution against their wide spread presence on retroviral vectors to be used for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN47,

title = {Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells},

author = {A. Hussain and K. Brahmbhatt and A. Priyani and M. Ahmed and T. A. Rizvi and C. Sharma},

doi = {10.1089/cbr.2010.0925},

issn = {1084-9785},

year  = {2011},

date = {2011-01-01},

urldate = {2011-01-01},

journal = {Cancer Biother Radiopharm},

volume = {26},

number = {5},

pages = {519-27},

abstract = {Administration of natural or synthetic agents to inhibit, delay, block, or reverse the initiation and promotional events associated with carcinogenesis opens a new avenue for cancer prevention and treatment to reduce cancer morbidity and mortality. Eugenol, a potential chemopreventive agent, is a component of clove and several other spices such as basil, cinnamon, and bay leaves. A number of reports have shown that eugenol possesses antiseptic, analgesic, antibacterial, and anticancer properties. The present study was undertaken to evaluate the chemopreventive potential of eugenol alone and in combination with a chemotherapeutic agent such as gemcitabine. Eugenol showed dose-dependent selective cytotoxicity toward HeLa cells in comparison to normal cells, pointing to its safe cytotoxicity profile. A combination of eugenol and gemcitabine induced growth inhibition and apoptosis at lower concentrations, compared with the individual drugs. The analysis of the data using a combination index showed combination index values of <1 indicating strong synergistic interaction. The combination thus may enhance the efficacy of gemcitabine at lower doses and minimize the toxicity on normal cells. In addition, the expression analysis of genes involved in apoptosis and inflammation revealed significant downregulation of Bcl-2, COX-2, and IL-1β on treatment with eugenol. Thus, the results suggest that eugenol exerts its anticancer activities via apoptosis induction and anti-inflammatory properties and also provide the first evidence demonstrating synergism between eugenol and gemcitabine, which may enhance the therapeutic index of prevention and/or treatment of cervical cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN67,

title = {SHAPE analysis of the FIV Leader RNA reveals a structural switch potentially controlling viral packaging and genome dimerization},

author = {J. C. Kenyon and S. J. Tanner and M. Legiewicz and P. S. Phillip and T. A. Rizvi and S. F. Le Grice and A. M. Lever},

doi = {10.1093/nar/gkr252},

issn = {0305-1048 (Print) 0305-1048},

year  = {2011},

date = {2011-01-01},

urldate = {2011-01-01},

journal = {Nucleic Acids Res},

volume = {39},

number = {15},

pages = {6692-704},

abstract = {Feline immunodeficiency virus (FIV) infects many species of cat, and is related to HIV, causing a similar pathology. High-throughput selective 2' hydroxyl acylation analysed by primer extension (SHAPE), a technique that allows structural interrogation at each nucleotide, was used to map the secondary structure of the FIV packaging signal RNA. Previous studies of this RNA showed four conserved stem-loops, extensive long-range interactions (LRIs) and a small, palindromic stem-loop (SL5) within the gag open reading frame (ORF) that may act as a dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Our analyses of wild-type (wt) and mutant RNAs suggest that although the four conserved stem-loops are static structures, the 5' and 3' regions previously shown to form LRI also adopt an alternative, yet similarly conserved conformation, in which the putative DIS is occluded, and which may thus favour translational and splicing functions over encapsidation. SHAPE and in vitro dimerization assays were used to examine SL5 mutants. Dimerization contacts appear to be made between palindromic loop sequences in SL5. As this stem-loop is located within the gag ORF, recognition of a dimeric RNA provides a possible mechanism for the specific packaging of genomic over spliced viral RNAs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN123,

title = {Ectopic myelinating oligodendrocytes in the dorsal spinal cord as a consequence of altered semaphorin 6D signaling inhibit synapse formation},

author = {J. R. Leslie and F. Imai and K. Fukuhara and N. Takegahara and T. A. Rizvi and R. H. Friedel and F. Wang and A. Kumanogoh and Y. Yoshida},

doi = {10.1242/dev.066076},

issn = {0950-1991 (Print) 0950-1991},

year  = {2011},

date = {2011-01-01},

urldate = {2011-01-01},

journal = {Development},

volume = {138},

number = {18},

pages = {4085-95},

abstract = {Different types of sensory neurons in the dorsal root ganglia project axons to the spinal cord to convey peripheral information to the central nervous system. Whereas most proprioceptive axons enter the spinal cord medially, cutaneous axons typically do so laterally. Because heavily myelinated proprioceptive axons project to the ventral spinal cord, proprioceptive axons and their associated oligodendrocytes avoid the superficial dorsal horn. However, it remains unclear whether their exclusion from the superficial dorsal horn is an important aspect of neural circuitry. Here we show that a mouse null mutation of Sema6d results in ectopic placement of the shafts of proprioceptive axons and their associated oligodendrocytes in the superficial dorsal horn, disrupting its synaptic organization. Anatomical and electrophysiological analyses show that proper axon positioning does not seem to be required for sensory afferent connectivity with motor neurons. Furthermore, ablation of oligodendrocytes from Sema6d mutants reveals that ectopic oligodendrocytes, but not proprioceptive axons, inhibit synapse formation in Sema6d mutants. Our findings provide new insights into the relationship between oligodendrocytes and synapse formation in vivo, which might be an important element in controlling the development of neural wiring in the central nervous system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}