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11. Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension

Author

Mohammed, Mazher, primary, Ogunlade, Blessing, additional, Elgazzaz, Mona, additional, Berdasco, Clara, additional, Lakkappa, Navya, additional, Ghita, Ioana, additional, Guidry, Jessie J, additional, Sriramula, Srinivas, additional, Xu, Jiaxi, additional, Restivo, Luke, additional, Mendiola Plá, Michelle A, additional, Bowles, Dawn E, additional, Beyer, Andreas M, additional, Yue, Xinping, additional, Lazartigues, Eric, additional, and Filipeanu, Catalin M, additional

Published
2023
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18. COVID-19 Infection Enhances Susceptibility to Oxidative Stress-Induced Parkinsonism.

Author

Smeyne, Richard Jay, Eells, Jeffrey B, Chatterjee, Debotri, Byrne, Matthew, Akula, Shaw M, Sriramula, Srinivas, O'Rourke, Dorcas P, Schmidt, Peter, Smeyne, Richard Jay, Eells, Jeffrey B, Chatterjee, Debotri, Byrne, Matthew, Akula, Shaw M, Sriramula, Srinivas, O'Rourke, Dorcas P, and Schmidt, Peter

Abstract

BACKGROUND: Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with those observed after pandemic influenza, there is a question whether a similar syndrome of postencephalic parkinsonism could follow coronavirus disease 2019 infection. OBJECTIVE: The goal of this study was to determine whether prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. METHODS: K18-hACE2 mice were infected with SARS-CoV-2 to induce mild-to-moderate disease. After 38 days of recovery, mice were administered a non-lesion-inducing dose of the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and euthanized 7 days later. Subsequent neuroinflammation and substantia nigra pars compacta (SNpc) dopaminergic (DA) neuron loss were determined and compared with SARS-CoV-2 or MPTP alone. RESULTS: K18-hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss after MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc DA neurons than SARS-CoV-2 or MPTP, respectively (P < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in both the SNpc and striatum of the SARS-CoV-2 + MPTP group compared with SARS-CoV-2 or MPTP alone. CONCLUSIONS: Our observations have important implications for long-term public health, given the number of people who have survived SARS-CoV-2 infection, as well as for future public policy regarding infection mitigation. However, it will be critical to determine whether other agents known to increase risk for PD also have synergistic effects with SARS-CoV-2 and are abrogated by vaccination. © 2022 The Authors.

Published
2022

29. The Angiotensin-Converting Enzyme 2/Angiogenesis-(1-7)/Mas Axis Confers Cardiopulmonary Protection against Lung Fibrosis and Pulmonary Hypertension

Author

Shenoy, Vinayak, Ferreira, Anderson J., Qi, Yanfei, Fraga-Silva, Rodrigo A., Díez-Freire, Carlos, Dooies, Autumn, Jun, Joo Yun, Sriramula, Srinivas, Mariappan, Nithya, Pourang, Dorna, Venugopal, Changaram S., Francis, Joseph, Reudelhuber, Timothy, Santos, Robson A., Patel, Jawaharlal M., Raizada, Mohan K., and Katovich, Michael J.

Published
2010
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36. Reliability Model and Sensitivity Analysis for Electrical/Electronic/Programmable Electronic Safety-Related Systems.

Author

Torres, Esperanza S., Sriramula, Srinivas, Celeita, David, and Ramos, Gustavo

Subjects
*ELECTRONIC systems, *SERVICE life, *SENSITIVITY analysis, *MARKOV processes, *NUCLEAR industry, *SYSTEM safety
Abstract

Nowadays, different industries such as nuclear, automotive, process, chemical, and oil and gas industry must meet specific requirements in order to keep and reduce safety risks to as low as reasonably practicable level. As a result, the number of electrical/electronic/programmable electronic safety-related systems (E/E/PES) to control, prevent, and mitigate hazardous events has increased. Moreover, new guidelines and procedures have been developed to guarantee the availability and function of safety systems over their service life. Based on Markov processes, this article discusses a reliability model to assess the integrity and verify the design of E/E/PES safety-related systems. The average probability of failure on demand and safety integrity level are used to determine the reliability performance of an E/E/PES in a low-demand mode of operation in accordance with the functional safety principles of the IEC 61508 and IEC 61511 standards. [ABSTRACT FROM AUTHOR]

Published
2020
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37. Aging influences cerebrovascular myogenic reactivity and BK channel function in a sex-specific manner.

Author

Reed, Joseph T, Pareek, Tanya, Sriramula, Srinivas, and Pabbidi, Mallikarjuna R

Subjects
VASCULAR smooth muscle, SPRAGUE Dawley rats, CEREBRAL arteries, MUSCLE cells
Abstract

Aims The myogenic reactivity of the middle cerebral arteries (MCA) protects the brain by altering the diameter in response to changes in lumen pressure. Large conductance potassium (BK) channels are known to regulate the myogenic reactivity, yet, it is not clear how aging alters the myogenic reactivity via the BK channel in males and females. Thus, we hypothesize that age-associated changes in BK channel subunits modulate the myogenic reactivity in a sex-specific manner. Methods and results We used vascular reactivity, patch-clamp, and biochemical methods to measure myogenic reactivity, BK channel function, and expression, respectively in cerebral vessels of adult and aged male and female Sprague Dawley rats. Our results suggest that aging and ovariectomy (OVX) exaggerated the myogenic reactivity of MCA in females but attenuated it in males. Aging induced outward eutrophic remodelling in females but inward hypertrophic remodelling in males. Aging decreased total, Kv, BK channel currents, and spontaneous transient outward currents (STOC) in vascular smooth muscle cells isolated from females, but not in males. Aging increased BKα subunit mRNA and protein both in males and females. However, aging decreased BKβ1 subunit protein and mRNA in females only. In males, BKβ1 mRNA is increased, but protein is decreased. Iberiotoxin-induced MCA constriction is lower in aged females but higher in aged males. Activation of BKα (10 µM NS1619) and BKβ1 (10 µM S-Equol) subunits failed to increase STOCs and were unable to decrease the myogenic reactivity of MCA in aged female but not in aged male rats. OVX decreased, but chronic supplementation of oestradiol restored BK channel expression and function. Conclusion Overall our results suggest that aging or OVX-associated downregulation of the BKβ1 expression and function in females results in exaggerated myogenic reactivity of MCA. However, age-associated increase in BK channel function in males attenuated myogenic reactivity of MCA. [ABSTRACT FROM AUTHOR]

Published
2020
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42. Rapid Identification of Mycobacterium tuberculosis Beijing Genotypes on the Basis of the Mycobacterial Interspersed Repetitive Unit Locus 26 Signature

Author

Sriramula Srinivas, Leonardo Antonio Sechi, Seyed E. Hasnain, Niyaz Ahmed, and K. Rajender Rao

Subjects
DNA, Bacterial, Microbiology (medical), Tuberculosis, Genotype, biology, Outbreak, Mycobacteriology and Aerobic Actinomycetes, Locus (genetics), Mycobacterium tuberculosis, Interspersed Repetitive Sequences, biology.organism_classification, medicine.disease, Virology, Bacterial Typing Techniques, Microbiology, Beijing, medicine, Humans, Letters to the Editor, Genotyping
Abstract

Mycobacterium tuberculosis Beijing strains are prevalent in many parts of the world and often give rise to large institutional outbreaks. Such highly transmissible strains, often associated with multidrug resistance, are likely underrepresented in outbreaks reported from developing countries, mainly due to nonavailability of fast detection methods suitable in epidemiological surveillance studies. We evaluated a PCR assay based on amplification of mycobacterial interspersed repetitive unit locus 26 as a stand-alone method for unambiguous identification of Beijing strains. The method was used on blinded samples from 10 standard strains whose Beijing status was already confirmed by spoligotyping. All 10 strains were accurately identified, and their profiles were corroborated successfully with spoligotypes. The method was also applied to 70 different non-Beijing clinical isolates from different countries to allow discrimination of isolates. Owing to its accuracy, simplicity, and rapidity, the assay can be employed in laboratory-level testing of isolates linked to certain outbreaks. The test can also be adopted for direct application on clinical samples to save time on culturing bacilli for genotyping.

Published
2006

43. Analysis of Genomic Downsizing on the Basis of Region-of-Difference Polymorphism Profiling of Mycobacterium tuberculosis Patient Isolates Reveals Geographic Partitioning

Author

Leonardo Antonio Sechi, Farhana Kauser, K. Rajender Rao, Sriramula Srinivas, Seyed E. Hasnain, Niyaz Ahmed, and Stefania Anna Lucia Zanetti

Subjects
Microbiology (medical), Tuberculosis, India, Virulence, Genomics, Libya, Biology, Polymerase Chain Reaction, Genome, law.invention, Mycobacterium tuberculosis, Bacterial Proteins, law, Peru, medicine, Humans, Genotyping, Polymerase chain reaction, Genetics, Polymorphism, Genetic, Mycobacteriology and Aerobic Actinomycetes, medicine.disease, biology.organism_classification, Angola, Gene Deletion, Genome, Bacterial, Bacteria
Abstract

Mycobacterium tuberculosis , the etiological agent of tuberculosis, has lost many coding and noncoding regions in its genome during the course of evolution. We performed region-of-difference (RD) analysis using PCR-based genotyping of 131 M. tuberculosis clinical isolates obtained from four different countries, namely, India, Peru, Libya, and Angola. Our studies revealed that RD patterns are often distinct for strains circulating in specific geographical regions and can be used to trace the descent and spread of an isolate from its original reservoir. We describe our findings, which show that no single isolate from the four countries ( n = 131) had all the 15 RDs either deleted or retained. Tuberculosis-specific deletion 1 (TbD1) was found to be conserved in 23% of the Indian isolates, indicating their possible ancient origin. RD9 was the most conserved region, RD11 was predominantly deleted, and RD6 was the most variable among the isolates in our collection irrespective of their geographic region. In contrast to earlier reports, our results demonstrate that the deletion of RD1 does not correlate with a decrease in the virulence potential of M. tuberculosis , as Indian isolates ( n = 30) examined by us were from diseased individuals and yet had lost the RD1 region. Our results further illustrated that the intactness of the RD5 region may be associated with increased virulence of the organism. This study highlights that the RDs in M. tuberculosis genomes are geographically distributed and specific and may possibly be associated with virulence spectrum.

Published
2005

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