174 results on '"Soteropoulos P"'
Search Results
2. Recovery of neurophysiological measures in post-COVID fatigue: a 12-month longitudinal follow-up study
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Maffitt, Natalie J., Germann, Maria, Baker, Anne M. E., Baker, Mark R., Baker, Stuart N., and Soteropoulos, Demetris S.
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- 2024
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3. Impact analysis of Advanced Driver Assistance Systems (ADAS) regarding road safety – computing reduction potentials
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Michael Aleksa, Andrea Schaub, Isabela Erdelean, Stephan Wittmann, Aggelos Soteropoulos, and Alexander Fürdös
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ADAS ,Reduction of accidents ,Impact on crashes ,Road safety impact ,Transportation engineering ,TA1001-1280 ,Transportation and communications ,HE1-9990 - Abstract
Abstract In the present study road safety impact analysis for certain advanced driver assistance systems (ADAS) was conducted. Based on a literature review, expert interviews and current adaptations in legislation, the most promising nine ADAS were selected. The impact was analysed based on statistical crash data from Austria. Factors such as infrastructure and weather conditions, market penetration, expected functionality of sensors, user acceptance and risk homeostasis were considered. A software tool was developed to calculate the crash reduction potential of the selected ADAS for the scenarios 2025, 2030 and 2040. The results show that the ADAS related to warning/braking have the greatest future reduction potential and could lead to a reduction of up to 8,700 crashes and 70 fatalities in Austria in 2040. In addition, the Intelligent Speed Assistance system would lead to an overall crash reduction of 8% compared to current crash numbers in Austria in 2040. The Turning Assistant for heavy goods vehicles shows the lowest reduction in crashes and casualties, but due to the highest severity per crash (93 fatalities per 1,000 crashes), it nevertheless provides an important contribution to the reduction of fatalities in road traffic. However, to benefit from the ADAS safety potential, it is highly relevant that these systems are used in a correct manner. In the future, it will be necessary to provide users with more information on the correct use, benefits and limitations of the respective ADAS and to integrate the use of these systems into driver education procedures and tests.
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- 2024
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4. Recovery of neurophysiological measures in post-COVID fatigue: a 12-month longitudinal follow-up study
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Natalie J. Maffitt, Maria Germann, Anne M. E. Baker, Mark R. Baker, Stuart N. Baker, and Demetris S. Soteropoulos
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Medicine ,Science - Abstract
Abstract One of the major consequences of the COVID-19 pandemic has been the significant incidence of persistent fatigue following resolution of an acute infection (i.e. post-COVID fatigue). We have shown previously that, in comparison to healthy controls, those suffering from post-COVID fatigue exhibit changes in muscle physiology, cortical circuitry, and autonomic function. Whether these changes preceded infection, potentially predisposing people to developing post-COVID fatigue, or whether the changes were a consequence of infection was unclear. Here we present results of a 12-month longitudinal study of 18 participants from the same cohort of post-COVID fatigue sufferers to investigate these correlates of fatigue over time. We report improvements in self-perception of the impact of fatigue via questionnaires, as well as significant improvements in objective measures of peripheral muscle fatigue and autonomic function, bringing them closer to healthy controls. Additionally, we found reductions in muscle twitch tension rise times, becoming faster than controls, suggesting that the improvement in muscle fatigability might be due to a process of adaptation rather than simply a return to baseline function.
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- 2024
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5. Differential gene expression of Caenorhabditis elegans grown on unmethylated sterols or 4α-methylsterols
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Merris Mark, Wang Tongsheng, Soteropoulos Patricia, and Lenard John
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transcription ,reverse transcription polymerase chain reaction ,microarray ,cholesterol ,lathosterol ,lophenol ,Biochemistry ,QD415-436 - Abstract
Transcriptional profiles of Caenorhabditis elegans grown on unmethylated sterols (desMSs) or on 4α-methylsterols (4MSs) were compared using microarrays. Thirty-four genes were upregulated and 2 were downregulated >2-fold by growth on 4MSs, including 13 cuticle collagen (col) genes, 1 cuticulin gene (cut-1), 2 groundhog-like (grl) genes, and 1 groundhog gene (grd-4); col-36 and grl-20 were increased 12- and 19-fold, respectively. Fifteen of these 17 genes have been assigned to metabolic mountain 17, suggesting coordinate 4MS-mediated regulation of expression. Quantitative RT-PCR was performed on 27–51 h old animals grown on cholesterol (a desMS) or lophenol (a 4MS). col-36 and grl-20 showed similar cyclic peaks of expression in cholesterol and similar alterations in lophenol, suggesting coregulation. Of six additional grl genes, only grl-3 was upregulated on lophenol; the rest were downregulated. Cyclicity of expression was lost or altered in all six. Nuclear receptor genes nhr-23, nhr-25, nhr-41, and daf-12 all showed cyclic expression in cholesterol and significant downregulation in lophenol by RT-PCR. Expression of the insulin-like receptor daf-2 was lower in lophenol, whereas that of its major downstream target daf-16 was higher. Thus, major changes in gene expression accompany growth on 4MSs, but with surprisingly little effect on normal growth and development.
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- 2007
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6. Cutting Edge: Neutrophils License the Maturation of Monocytes into Effective Antifungal Effectors.
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Espinosa, Vanessa, Dutta, Orchi, Wang, Keyi, Chang, Yun-Juan, Soteropoulos, Patricia, Hohl, Tobias, Siracusa, Mark, Rivera, Amariliz, and Heung, Lena
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Mice ,Animals ,Monocytes ,Neutrophils ,Antifungal Agents ,Reactive Oxygen Species ,Aspergillus fumigatus - Abstract
Neutrophils are critical for the direct eradication of Aspergillus fumigatus conidia, but whether they mediate antifungal defense beyond their role as effectors is unclear. In this study, we demonstrate that neutrophil depletion impairs the activation of protective antifungal CCR2+ inflammatory monocytes. In the absence of neutrophils, monocytes displayed limited differentiation into monocyte-derived dendritic cells, reduced formation of reactive oxygen species, and diminished conidiacidal activity. Upstream regulator analysis of the transcriptional response in monocytes predicted a loss of STAT1-dependent signals as the potential basis for the dysfunction seen in neutrophil-depleted mice. We find that conditional removal of STAT1 on CCR2+ cells results in diminished antifungal monocyte responses, whereas exogenous administration of IFN-γ to neutrophil-depleted mice restores monocyte-derived dendritic cell maturation and reactive oxygen species production. Altogether, our findings support a critical role for neutrophils in antifungal immunity not only as effectors but also as important contributors to antifungal monocyte activation, in part by regulating STAT1-dependent functions.
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- 2022
7. Long COVID: mechanisms, risk factors and recovery
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Rónan Astin, Amitava Banerjee, Mark R. Baker, Melanie Dani, Elizabeth Ford, James H. Hull, Phang Boon Lim, Melitta McNarry, Karl Morten, Oliver O'Sullivan, Etheresia Pretorius, Betty Raman, Demetris S. Soteropoulos, Maxime Taquet, and Catherine N. Hall
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cardiovascular ,coagulation ,dysautonomia ,fatigue ,long COVID ,ME/CFS ,Physiology ,QP1-981 - Abstract
Abstract Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS‐CoV‐2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post‐viral illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post‐viral syndromes. Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population. We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID‐related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction. The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve. We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro‐clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations. Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.
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- 2023
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8. Involvement of HTLV-I Tax and CREB in aneuploidy: a bioinformatics approach
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Pumfery Anne, Soteropoulos Patricia, Galante Anthony, McCaffery Timothy, Cahan Patrick, Strouss Katharine, Klase Zachary, Gupta Madhur V, de la Fuente Cynthia, Fujii Masahiro, and Kashanchi Fatah
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Adult T-cell leukemia (ATL) is a complex and multifaceted disease associated with human T-cell leukemia virus type 1 (HTLV-I) infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-I transformed cells by either directly disrupting cellular factors (protein-protein interactions) or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-κB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. Results We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT) exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703). To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgt1 promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. Conclusion These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions.
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- 2006
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9. Noise filtering and nonparametric analysis of microarray data underscores discriminating markers of oral, prostate, lung, ovarian and breast cancer
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Dermody James J, Cheng Jeff, Cody Michael J, Aris Virginie M, Soteropoulos Patricia, Recce Michael, and Tolias Peter P
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background A major goal of cancer research is to identify discrete biomarkers that specifically characterize a given malignancy. These markers are useful in diagnosis, may identify potential targets for drug development, and can aid in evaluating treatment efficacy and predicting patient outcome. Microarray technology has enabled marker discovery from human cells by permitting measurement of steady-state mRNA levels derived from thousands of genes. However many challenging and unresolved issues regarding the acquisition and analysis of microarray data remain, such as accounting for both experimental and biological noise, transcripts whose expression profiles are not normally distributed, guidelines for statistical assessment of false positive/negative rates and comparing data derived from different research groups. This study addresses these issues using Affymetrix HG-U95A and HG-U133 GeneChip data derived from different research groups. Results We present here a simple non parametric approach coupled with noise filtering to identify sets of genes differentially expressed between the normal and cancer states in oral, breast, lung, prostate and ovarian tumors. An important feature of this study is the ability to integrate data from different laboratories, improving the analytical power of the individual results. One of the most interesting findings is the down regulation of genes involved in tissue differentiation. Conclusions This study presents the development and application of a noise model that suppresses noise, limits false positives in the results, and allows integration of results from individual studies derived from different research groups.
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- 2004
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10. Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma
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Soroceanu, Liliana, Matlaf, Lisa, Khan, Sabeena, Akhavan, Armin, Singer, Eric, Bezrookove, Vladimir, Decker, Stacy, Ghanny, Saleena, Hadaczek, Piotr, Bengtsson, Henrik, Ohlfest, John, Luciani-Torres, Maria-Gloria, Harkins, Lualhati, Perry, Arie, Guo, Hong, Soteropoulos, Patricia, and Cobbs, Charles S
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Clinical Research ,Biotechnology ,Neurosciences ,Brain Disorders ,Brain Cancer ,Rare Diseases ,Stem Cell Research ,Infectious Diseases ,Stem Cell Research - Nonembryonic - Human ,Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Animals ,Antigens ,Viral ,Apoptosis ,Brain Neoplasms ,Cytomegalovirus ,Cytomegalovirus Infections ,Disease Models ,Animal ,Gene Knockdown Techniques ,Glioblastoma ,Glioma ,Humans ,Immediate-Early Proteins ,Mice ,Inbred BALB C ,MicroRNAs ,Neoplastic Stem Cells ,SOXB1 Transcription Factors ,Tumor Cells ,Cultured ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Glioblastoma (GBM) is the most common and aggressive human brain tumor. Human cytomegalovirus (HCMV) immediate-early (IE) proteins that are endogenously expressed in GBM cells are strong viral transactivators with oncogenic properties. Here, we show how HCMV IEs are preferentially expressed in glioma stem-like cells (GSC), where they colocalize with the other GBM stemness markers, CD133, Nestin, and Sox2. In patient-derived GSCs that are endogenously infected with HCMV, attenuating IE expression by an RNAi-based strategy was sufficient to inhibit tumorsphere formation, Sox2 expression, cell-cycle progression, and cell survival. Conversely, HCMV infection of HMCV-negative GSCs elicited robust self-renewal and proliferation of cells that could be partially reversed by IE attenuation. In HCMV-positive GSCs, IE attenuation induced a molecular program characterized by enhanced expression of mesenchymal markers and proinflammatory cytokines, resembling the therapeutically resistant GBM phenotype. Mechanistically, HCMV/IE regulation of Sox2 occurred via inhibition of miR-145, a negative regulator of Sox2 protein expression. In a spontaneous mouse model of glioma, ectopic expression of the IE1 gene (UL123) specifically increased Sox2 and Nestin levels in the IE1-positive tumors, upregulating stemness and proliferation markers in vivo. Similarly, human GSCs infected with the HCMV strain Towne but not the IE1-deficient strain CR208 showed enhanced growth as tumorspheres and intracranial tumor xenografts, compared with mock-infected human GSCs. Overall, our findings offer new mechanistic insights into how HCMV/IE control stemness properties in GBM cells.
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- 2015
11. Entry of the bat influenza H17N10 virus into mammalian cells is enabled by the MHC class II HLA-DR receptor
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Giotis, Efstathios S., Carnell, George, Young, Erik F., Ghanny, Saleena, Soteropoulos, Patricia, Wang, Lin-Fa, Barclay, Wendy S., Skinner, Michael A., and Temperton, Nigel
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- 2019
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12. Comprehensive Analysis of Disease Pathology in Immunocompetent and Immunocompromised Hosts following Pulmonary SARS-CoV-2 Infection
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Santhamani Ramasamy, Afsal Kolloli, Ranjeet Kumar, Seema Husain, Patricia Soteropoulos, Theresa L. Chang, and Selvakumar Subbian
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immune suppression ,COVID-19 ,immunopathology ,extrapulmonary ,antibody ,RNAseq ,Biology (General) ,QH301-705.5 - Abstract
The Coronavirus disease 2019 (COVID-19) pandemic disproportionately affects immunocompetent and immunocompromised individuals, with the latter group being more vulnerable to severe disease and death. However, the differential pathogenesis of SARS-CoV-2 in the context of a specific immunological niche remains unknown. Similarly, systematic analysis of disease pathology in various extrapulmonary organs in immunocompetent and immunocompromised hosts during SARS-CoV-2 infection is not fully understood. We used a hamster model of SARS-CoV-2 infection, which recapitulates the pathophysiology of patients with mild-to-moderate COVID-19, to determine the dynamics of SARS-CoV-2 replication and histopathology at organ-level niches and map how COVID-19 symptoms vary in different immune contexts. Hamsters were intranasally infected with low (LD) or high (HD) inoculums of SARS-CoV-2, and the kinetics of disease pathology and viral load in multiple organs, antibody response, inflammatory cytokine expression, and genome-wide lung transcriptome by RNAseq analysis were determined and compared against corresponding responses from chemically induced immunocompromised hamsters. We observed transient body weight loss proportional to the SARS-CoV-2 infectious dose in immunocompetent hamsters. The kinetics of viral replication and peak viral loads were similar between LD and HD groups, although the latter developed more severe disease pathology in organs. Both groups generated a robust serum antibody response. In contrast, infected immunocompromised animals showed more prolonged body weight loss and mounted an inadequate SARS-CoV-2-neutralizing antibody response. The live virus was detected in the pulmonary and extrapulmonary organs for extended periods. These hamsters also had persistent inflammation with severe bronchiolar-alveolar hyperplasia/metaplasia. Consistent with the differential disease presentation, distinct changes in inflammation and immune cell response pathways and network gene expression were seen in the lungs of SARS-CoV-2-infected immunocompetent and immunocompromised animals.
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- 2022
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13. Mycobacterium tuberculosis progresses through two phases of latent infection in humans
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Colangeli, Roberto, Gupta, Aditi, Vinhas, Solange Alves, Chippada Venkata, Uma Deepthi, Kim, Soyeon, Grady, Courtney, Jones-López, Edward C., Soteropoulos, Patricia, Palaci, Moisés, Marques-Rodrigues, Patrícia, Salgame, Padmini, Ellner, Jerrold J., Dietze, Reynaldo, and Alland, David
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- 2020
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14. The Role of Immunological Synapse in Predicting the Efficacy of Chimeric Antigen Receptor (CAR) Immunotherapy
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Liu, Dongfang, Badeti, Saiaditya, Dotti, Gianpietro, Jiang, Jie-gen, Wang, He, Dermody, James, Soteropoulos, Patricia, Streck, Deanna, Birge, Raymond B., and Liu, Chen
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- 2020
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15. Publisher Correction: Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
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Ngô, Huân M., Zhou, Ying, Lorenzi, Hernan, Wang, Kai, Kim, Taek-Kyun, Zhou, Yong, El Bissati, Kamal, Mui, Ernest, Fraczek, Laura, Rajagopala, Seesandra V., Roberts, Craig W., Henriquez, Fiona L., Montpetit, Alexandre, Blackwell, Jenefer M., Jamieson, Sarra E., Wheeler, Kelsey, Begeman, Ian J., Naranjo-Galvis, Carlos, Alliey-Rodriguez, Ney, Davis, Roderick G., Soroceanu, Liliana, Cobbs, Charles, Steindler, Dennis A., Boyer, Kenneth, Noble, A. Gwendolyn, Swisher, Charles N., Heydemann, Peter T., Rabiah, Peter, Withers, Shawn, Soteropoulos, Patricia, Hood, Leroy, and McLeod, Rima
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- 2019
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16. Hst3p, a histone deacetylase, promotes maintenance of Saccharomyces cerevisiae chromosome III lacking efficient replication origins
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Irene, Carmela, Theis, James F., Gresham, David, Soteropoulos, Patricia, and Newlon, Carol S.
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- 2016
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17. Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
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Ngô, Huân M., Zhou, Ying, Lorenzi, Hernan, Wang, Kai, Kim, Taek-Kyun, Zhou, Yong, El Bissati, Kamal, Mui, Ernest, Fraczek, Laura, Rajagopala, Seesandra V., Roberts, Craig W., Henriquez, Fiona L., Montpetit, Alexandre, Blackwell, Jenefer M., Jamieson, Sarra E., Wheeler, Kelsey, Begeman, Ian J., Naranjo-Galvis, Carlos, Alliey-Rodriguez, Ney, Davis, Roderick G., Soroceanu, Liliana, Cobbs, Charles, Steindler, Dennis A., Boyer, Kenneth, Noble, A. Gwendolyn, Swisher, Charles N., Heydemann, Peter T., Rabiah, Peter, Withers, Shawn, Soteropoulos, Patricia, Hood, Leroy, and McLeod, Rima
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- 2017
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18. Long COVID: Mechanismen, Risikofaktoren und Genesung
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Astin, Rónan, Banerjee, Amitava, Baker, Mark R., Dani, Melanie, Ford, Elizabeth, Hull, James H., Lim, Phang Boon, McNarry, Melitta, Morten, Karl, O’Sullivan, Oliver, Pretorius, Etheresia, Raman, Betty, Soteropoulos, Demetris S., Taquet, Maxime, and Hall, Catherine N.
- Abstract
Long COVID, die lang anhaltende Krankheit und Erschöpfung, die bei einem kleinen Teil der SARS-CoV-2-Infizierten auftritt, stellt eine zunehmende Belastung für die Betroffenen und die Gesellschaft dar. Eine virtuelle Tagung der Physiological Society im Februar 2022 brachte Kliniker und Forscher zusammen, um das aktuelle Verständnis der Mechanismen, Risikofaktoren und Genesung nach Long COVID zu erörtern. In dieser Übersichtsarbeit werden die Themen behandelt, die sich aus dieser Tagung ergeben haben. Die Übersichtsarbeit befasst sich mit der Natur von Long COVID, untersucht den Zusammenhang mit anderen postviralen Erkrankungen wie der myalgischen Enzephalomyelitis/dem chronischen Erschöpfungssyndrom und zeigt auf, wie die Forschung zu Long COVID helfen kann, Patienten mit allen möglichen postviralen Syndromen besser zu unterstützen. Die Forschung zu Long COVID hat besonders rasche Fortschritte bei Bevölkerungsgruppen gemacht, die ihre körperliche Leistungsfähigkeit routinemäßig überwachen, insbesondere beim Militär und bei Leistungssportlern. In der Übersichtsarbeit wird hervorgehoben, inwiefern das hohe Niveau von Diagnose, Intervention und Erfolgskontrolle in diesen aktiven Bevölkerungsgruppen Informationen über Managementstrategien für die Allgemeinbevölkerung liefern kann. Anschließend wird untersucht, wie eine Schlüsselkomponente der Leistungsüberwachung bei diesen aktiven Bevölkerungsgruppen, das kardiopulmonale Training, Long-COVID-bedingte Veränderungen in der Physiologie aufdeckt – einschließlich Veränderungen der peripheren Muskelfunktion, der ventilatorischen Ineffizienz und der autonomen Dysfunktion. Das Wesen und die Auswirkungen der Dysautonomie werden im Zusammenhang mit dem posturalen orthostatischen Tachykardiesyndrom, der Fatigue und den Behandlungsstrategien, die darauf abzielen, der Überaktivierung des Sympathikus durch Stimulation des Vagusnervs entgegenzuwirken, erörtert. Anschließend untersuchen wir die Mechanismen, die den Symptomen von Long COVID zugrunde liegen. Dabei konzentrieren wir uns auf die gestörte Sauerstoffversorgung durch Mikrokoagulation und die Störung des zellulären Energiestoffwechsels, bevor wir Behandlungsstrategien betrachten, die direkt oder indirekt auf diese Mechanismen abzielen. Dazu gehören ein fernbetreutes Atemmuskeltraining und integrierte Versorgungspfade, die Rehabilitation und medikamentöse Interventionen mit der Erforschung des Zugangs zur Long-COVID-Versorgung in verschiedenen Bevölkerungsgruppen kombinieren. Insgesamt zeigt diese Übersichtsarbeit, wie im Rahmen der physiologischen Forschung die bei Long COVID auftretenden Veränderungen aufgedeckt werden und wie verschiedene therapeutische Strategien zur Bekämpfung dieser Erkrankung entwickelt und getestet werden.
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- 2023
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19. Vaccination with an Attenuated Ferritin Mutant Protects Mice against Virulent Mycobacterium tuberculosis
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Selvakumar Subbian, Ruchi Pandey, Patricia Soteropoulos, and G. Marcela Rodriguez
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Mycobacterium tuberculosis the causative agent of tuberculosis affects millions of people worldwide. New tools for treatment and prevention of tuberculosis are urgently needed. We previously showed that a ferritin (bfrB) mutant of M. tuberculosis has altered iron homeostasis and increased sensitivity to antibiotics and to microbicidal effectors produced by activated macrophages. Most importantly, M. tuberculosis lacking BfrB is strongly attenuated in mice, especially, during the chronic phase of infection. In this study, we examined whether immunization with a bfrB mutant could confer protection against subsequent infection with virulent M. tuberculosis in a mouse model. The results show that the protection elicited by immunization with the bfrB mutant is comparable to BCG vaccination with respect to reduction of bacterial burden. However, significant distinctions in the disease pathology and host genome-wide lung transcriptome suggest improved containment of Mtb infection in animals vaccinated with the bfrB mutant, compared to BCG. We found that downmodulation of inflammatory response and enhanced fibrosis, compared to BCG vaccination, is associated with the protective response elicited by the bfrB mutant.
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- 2015
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20. Novel, immediately druggable targets in the ARK1 model of uterine serous papillary carcinoma (USPC): Proof-of-principle and clinical implications of blocking oncologically relevant posttranslational hydroxylations with a pioneer drug
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Hanauske-Abel, H.M., primary, Singh, S., additional, Hoque, M., additional, Husain, S., additional, Hanauske, A.R., additional, Soteropoulos, P., additional, and Cracchiolo, B.M., additional
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- 2020
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21. Genome-directed identification of novel, immediately druggable targets in uterine serous papillary carcinoma (USPC)
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Hanauske-Abel, H.M., primary, Singh, S., additional, Hoque, M., additional, Husain, S., additional, Hanauske, A.R., additional, Soteropoulos, P., additional, and Cracchiolo, B.M., additional
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- 2020
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22. Salmonid microarrays identify intestinal genes that reliably monitor P deficiency in rainbow trout aquaculture
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Kirchner, S., McDaniel, N. K., Sugiura, S. H., Soteropoulos, P., Tian, B., Fletcher, J. W., and Ferraris, R. P.
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- 2007
23. Arrayed Nanohydrogels for Protein Array Technology
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Saaem, I., Papasotiropoulos, V., Wang, T., Soteropoulos, P., and Libera, M.
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- 2005
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24. Molecular genetic probing of energy coupling by the yeast plasma membrane proton pump
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SOTEROPOULOS, P., WANG, G., and PERLIN, D. S.
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- 1998
25. Energy metabolism pathways in rat muscle under conditions of simulated microgravity
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Stein, T.P., Schluter, M.D., Galante, A.T., Soteropoulos, P., Tolias, P.P., Grindeland, R.E., Moran, M.M., Wang, T.J., Polansky, M., and Wade, C.E.
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- 2002
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26. Age and road safety performance: Focusing on elderly and young drivers.
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Lyon, Craig, Mayhew, Dan, Granié, Marie-Axelle, Robertson, Robyn, Vanlaar, Ward, Woods-Fry, Heather, Thevenet, Chloé, Furian, Gerald, and Soteropoulos, Aggelos
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The existing literature on young and elderly drivers indicates that they have the highest crash risks compared to other age groups of drivers. This study improves our understanding of the risk factors contributing to young and elderly drivers' elevated crash risk by examining self-report data from the E -Survey of Road User's Safety Attitudes (ESRA). The primary objective of this study is to compare the attitudes and behaviours of young, elderly, and middle-age drivers in Canada, the United States, and Europe. The main focus is on the practice of driving while distracted by mobile phones and driving while fatigued, as these are two dangerous behaviours that demonstrate the impact age may have. The analyses consistently showed that there are differences in the responses attributable to age. In all regions, drivers aged 18–21 years consistently reported higher rates of distracted and fatigued driving and higher rates of perceived social and personal acceptability of these behaviours than drivers aged 35–54 years. Elderly drivers aged 65+ years reported even lower rates of these behaviours and acceptability. Young drivers were also the least likely to believe that distraction and fatigue are frequent causes of road crashes, while elderly drivers were the most likely to believe this. This pattern with respect to age repeats in the support for policy measures as well; young drivers are least likely to support zero tolerance policies for mobile phone use when driving, while elderly drivers are the most likely to support this measure. Multivariate logistic regression modeling confirmed that elderly drivers were the least likely to engage in the use of mobile phones while driving or driving while fatigued. Statistically significant results showed that the middle-age group was less likely than young drivers to read a text message/email or check social media while driving and driving while fatigued. • Young drivers (18–21 years) reported higher rates of distracted and fatigued driving than middle-age drivers (35–54 years). • Young drivers also showed higher rates of perceived social and personal acceptability of these behaviours. • Elderly drivers (65+ years) reported even lower rates of these behaviours and acceptability. • These trends are consistent across Canada, the United States, and Europe. [ABSTRACT FROM AUTHOR]
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- 2020
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27. Differential gene expression in trigeminal ganglia of male and female rats following chronic constriction of the infraorbital nerve
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Korczeniewska, O.A., primary, Husain, S., additional, Khan, J., additional, Eliav, E., additional, Soteropoulos, P., additional, and Benoliel, R., additional
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- 2018
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28. A Framework for Assessing Use Cases of high and full Driving Automation based on transport-related Experiences
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Mitteregger, Mathias, Soteropoulos, Aggelos, and Berger, Martin
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- 2019
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29. Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma
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Singer, E, primary, Judkins, J, additional, Salomonis, N, additional, Matlaf, L, additional, Soteropoulos, P, additional, McAllister, S, additional, and Soroceanu, L, additional
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- 2015
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30. DR-06 * REACTIVE OXYGEN SPECIES MEDIATE THERAPEUTIC RESPONSE AND RESISTANCE IN GLIOBLASTOMA
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Singer, E., primary, Judkins, J., additional, Salomonis, N., additional, Soteropoulos, P., additional, McAllister, S., additional, and Soroceanu, L., additional
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- 2014
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31. “I’m a news junkie . . . I like being informed”: Mobile news use by a newspaper’s digital subscribers
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Incollingo, Jacqueline Soteropoulos
- Abstract
A mixed methods research project combining quantitative online survey results with semistructured interview data explored how a major metropolitan newspaper’s digital subscribers engage with mobile news. Themes of continuity indicate that motivations in traditional newspaper use remain salient in mobile news: information-seeking, the pleasure of reading and powerful daily habits surrounding news use. In addition, participants’ responses suggest additional situational or process gratifications from using mobile media devices, in addition to gratifications derived from content.
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- 2018
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32. Time-Course Progression of Whole Transcriptome Expression Changes of Trigeminal Ganglia Compared to Dorsal Root Ganglia in Rats Exposed to Nerve Injury
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Korczeniewska, Olga A., Husain, Seema, Hoque, Mainul, Soteropoulos, Patricia, Khan, Junad, Eliav, Eli, and Benoliel, Rafael
- Abstract
Mechanisms underlying neuropathic pain (NP) are complex with multiple genes, their interactions, environmental and epigenetic factors being implicated. Transcriptional changes in the trigeminal (TG) and dorsal root (DRG) ganglia have been implicated in the development and maintenance of NP. Despite efforts to unravel molecular mechanisms of NP, many remain unknown. Also, most of the studies focused on the spinal system. Although the spinal and trigeminal systems share some of the molecular mechanisms, differences exist. We used RNA-sequencing technology to identify differentially expressed genes (DEGs) in the TG and DRG at baseline and 3 time points following the infraorbital or sciatic nerve injuries, respectively. Pathway analysis and comparison analysis were performed to identify differentially expressed pathways. Additionally, upstream regulator effects were investigated in the two systems. DEG (differentially expressed genes) analyses identified 3,225 genes to be differentially expressed between TG and DRG in naïve animals, 1,828 genes 4 days post injury, 5,644 at day 8 and 9,777 DEGs at 21 days postinjury. A comparison of top enriched canonical pathways revealed that a number of signaling pathway was significantly inhibited in the TG and activated in the DRG at 21 days postinjury. Finally, CORT upstream regulator was predicted to be inhibited in the TG while expression levels of the CSF1 upstream regulator were significantly elevated in the DRG at 21 days postinjury. This study provides a basis for further in-depth studies investigating transcriptional changes, pathways, and upstream regulation in TG and DRG in rats exposed to peripheral nerve injuries.
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- 2023
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33. Hydrogel-Based Protein Nanoarrays
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Saaem, I., primary, Papasotiropoulos, V., additional, Wang, T., additional, Soteropoulos, P., additional, and Libera, M., additional
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- 2007
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34. E-beam-patterned hydrogels to control nanoscale surface bioactivity
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Krsko, P., primary, Saaem, I., additional, Clancy, R., additional, Geller, H., additional, Soteropoulos, P., additional, and Libera, M., additional
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- 2005
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35. GENE EXPRESSION IN LUNG TISSUE AFTER TRAUMAHEMORRHAGIC SHOCK IS ALTERED BY MESENTERIC LYMPH DUCT LIGATION.
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Chu, H B, primary, Hasko, G, additional, Xu, D Z, additional, Németh, Z H, additional, Galante, A, additional, Soteropoulos, P, additional, Tolias, P P, additional, and Deitch, E A, additional
- Published
- 2002
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36. DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition
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Nesic, O., primary, Svrakic, N.M., additional, Xu, G-Y., additional, McAdoo, D., additional, Westlund, K. N., additional, Hulsebosch, C. E., additional, Ye, Zeiming, additional, Galante, A., additional, Soteropoulos, P., additional, Tolias, P., additional, Young, W., additional, Hart, R.P., additional, and Perez-Polo, J.R., additional
- Published
- 2002
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37. Carbonic anhydrase enzymes regulate mast cell–mediated inflammation
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Henry, Everett K., Sy, Chandler B., Inclan-Rico, Juan M., Espinosa, Vanessa, Ghanny, Saleena S., Dwyer, Daniel F., Soteropoulos, Patricia, Rivera, Amariliz, and Siracusa, Mark C.
- Abstract
Type 2 cytokine responses are necessary for the development of protective immunity to helminth parasites but also cause the inflammation associated with allergies and asthma. Recent studies have found that peripheral hematopoietic progenitor cells contribute to type 2 cytokine–mediated inflammation through their enhanced ability to develop into mast cells. In this study, we show that carbonic anhydrase (Car) enzymes are up-regulated in type 2–associated progenitor cells and demonstrate that Car enzyme inhibition is sufficient to prevent mouse mast cell responses and inflammation after Trichinella spiralis infection or the induction of food allergy–like disease. Further, we used CRISPR/Cas9 technology and illustrate that genetically editing Car1 is sufficient to selectively reduce mast cell development. Finally, we demonstrate that Car enzymes can be targeted to prevent human mast cell development. Collectively, these experiments identify a previously unrecognized role for Car enzymes in regulating mast cell lineage commitment and suggest that Car enzyme inhibitors may possess therapeutic potential that can be used to treat mast cell–mediated inflammation.
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- 2016
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38. Alkylation of cysteine 89 of the gamma subunit of chloroplast coupling factor 1 with N-ethylmaleimide alters nucleotide interactions.
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Soteropoulos, P., primary, Ong, A.M., additional, and McCarty, R.E., additional
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- 1994
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39. Modifications of the gamma subunit of chloroplast coupling factor 1 alter interactions with the inhibitory epsilon subunit.
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Soteropoulos, P, primary, Süss, K.H., additional, and McCarty, R.E., additional
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- 1992
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40. Global Transcriptional Profile of Mycobacterium tuberculosis during THP-1 Human Macrophage Infection
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Fontán, Patricia, Aris, Virginie, Ghanny, Saleena, Soteropoulos, Patricia, and Smith, Issar
- Abstract
During lung infection, Mycobacterium tuberculosis resides in macrophages and subverts the bactericidal mechanisms of these professional phagocytes. Comprehension of this host-pathogen relationship is fundamental for the development of new therapies to cure and prevent tuberculosis. In this work, we analyzed the transcriptional profile of M. tuberculosis infecting human macrophage-like THP-1 cells in order to identify putative bacterial pathogenic factors that can be relevant for the intracellular survival of M. tuberculosis. We compared the gene expression profile of M. tuberculosis H37Rv after 4 h and 24 h of infection of human macrophage-like THP-1 cells with the gene expression profile of the strain growing exponentially in broth cultures. We found 585 genes expressed differentially by intracellular M. tuberculosis. An analysis of the gene expression profile of M. tuberculosis inside THP-1 cells suggests the perturbation of the cell envelope as a major intracellular stress inside THP-1 macrophages.
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- 2008
41. Global Transcriptional Profile of Mycobacterium tuberculosisduring THP-1 Human Macrophage Infection
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Fontán, Patricia, Aris, Virginie, Ghanny, Saleena, Soteropoulos, Patricia, and Smith, Issar
- Abstract
ABSTRACTDuring lung infection, Mycobacterium tuberculosisresides in macrophages and subverts the bactericidal mechanisms of these professional phagocytes. Comprehension of this host-pathogen relationship is fundamental for the development of new therapies to cure and prevent tuberculosis. In this work, we analyzed the transcriptional profile of M. tuberculosisinfecting human macrophage-like THP-1 cells in order to identify putative bacterial pathogenic factors that can be relevant for the intracellular survival of M. tuberculosis.We compared the gene expression profile of M. tuberculosisH37Rv after 4 h and 24 h of infection of human macrophage-like THP-1 cells with the gene expression profile of the strain growing exponentially in broth cultures. We found 585 genes expressed differentially by intracellular M. tuberculosis. An analysis of the gene expression profile of M. tuberculosisinside THP-1 cells suggests the perturbation of the cell envelope as a major intracellular stress inside THP-1 macrophages.
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- 2008
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42. MOLECULAR SIGNATURES OF TRAUMA-HEMORRHAGIC SHOCK-INDUCED LUNG INJURY
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Feinman, Rena, Deitch, Edwin A., Aris, Virginie, Chu, Hung B., Abungu, Billy, Caputo, Francis J., Galante, Anthony, Xu, DaZhong, Lu, Qi, Colorado, Iriana, Streck, Deanna, Dermody, James, and Soteropoulos, Patricia
- Abstract
The etiology of trauma-hemorrhagic shock (T/HS)-induced acute lung injury has been difficult to elucidate because of, at least in part, the inability of in vivostudies to separate the noninjurious pulmonary effects of trauma-hemorrhage from the tissue-injurious ones. To circumvent this in vivolimitation, we used a model of T/HS in which T/HS lung injury was abrogated by dividing the mesenteric lymph duct. In this way, it was possible to separate the pulmonary injurious response from the noninjurious systemic response to T/HS by comparing the pulmonary molecular responses of rats subjected to T/HS, which did and did not develop lung injury, with those of nonshocked rats. Using high-density oligonucleotide arrays and treatment group comparisons of whole lung tissue collected at 3 h after the end of the shock or sham-shock period, 139 of 8,799 assessed genes were identified by significant analysis of microarrays. Hemorrhage without the secondary effects of lung injury modulated the expression of 21 genes such as interleukin 1, metallothionein-2, and myeloctomatosis oncogene (c-myc). In response to injury, 42 genes were identified to be differentially expressed. Upregulated genes included the L1 retroposon and guanine deaminase, whereas downregulated genes included catalase and superoxide dismutase 1. Real-time polymerase chain reaction confirmed the differential expression for selected genes. PathwayAssist analysis identified interleukin 1 as a central regulator of two subpathways of stress response-related genes (c-mycand superoxide dismutase 1/catalase) as well as several unrelated genes such as lipoprotein lipase. Our model system provided a unique opportunity to distinguish the molecular changes associated with T/HS-induced acute lung injury from the systemic molecular response to T/HS.
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- 2007
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43. Differential gene expression of Caenorhabditis elegansgrown on unmethylated sterols or 4α-methylsterols
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Mark, Merris, Tongsheng, Wang, Patricia, Soteropoulos, and John, Lenard
- Abstract
Transcriptional profiles of Caenorhabditis elegansgrown on unmethylated sterols (desMSs) or on 4α-methylsterols (4MSs) were compared using microarrays. Thirty-four genes were upregulated and 2 were downregulated >2-fold by growth on 4MSs, including 13 cuticle collagen (col) genes, 1 cuticulin gene (cut-1), 2 groundhog-like (grl) genes, and 1 groundhog gene (grd-4); col-36and grl-20were increased 12- and 19-fold, respectively. Fifteen of these 17 genes have been assigned to metabolic mountain 17, suggesting coordinate 4MS-mediated regulation of expression. Quantitative RT-PCR was performed on 27–51 h old animals grown on cholesterol (a desMS) or lophenol (a 4MS). col-36and grl-20showed similar cyclic peaks of expression in cholesterol and similar alterations in lophenol, suggesting coregulation. Of six additional grlgenes, only grl-3was upregulated on lophenol; the rest were downregulated. Cyclicity of expression was lost or altered in all six. Nuclear receptor genes nhr-23, nhr-25, nhr-41, and daf-12all showed cyclic expression in cholesterol and significant downregulation in lophenol by RT-PCR. Expression of the insulin-like receptor daf-2was lower in lophenol, whereas that of its major downstream target daf-16was higher. Thus, major changes in gene expression accompany growth on 4MSs, but with surprisingly little effect on normal growth and development.
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- 2007
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44. Analysis of Epstein-Barr virus reservoirs in paired blood and breast cancer primary biopsy specimens by real time PCR
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Perkins, R, Sahm, Katherine, Marando, Cindy, Dickson-Witmer, Diana, Pahnke, Gregory, Mitchell, Mark, Petrelli, Nicholas, Berkowitz, Irving, Soteropoulos, Patricia, Aris, Virginie, Dunn, Stephen, and Krueger, Leslie
- Abstract
Epstein-Barr virus (EBV) is present in over 90% of the world's population. This infection is considered benign, even though in limited cases EBV is associated with infectious and neoplastic conditions. Over the past decade, the EBV association with breast cancer has been constantly debated. Adding to this clinical and biological uncertainty, different techniques gave contradictory results for the presence of EBV in breast carcinoma specimens. In this study, minor groove binding (MGB)-TaqMan real time PCR was used to detect the presence of EBV DNA in both peripheral blood and tumor samples of selected patients. Peripheral blood and breast carcinoma specimens from 24 patients were collected. DNA was extracted and then amplified by MGB-TaqMan real time PCR. Of 24 breast tumor specimens, 11 (46%) were positive for EBV DNA. Of these 11 breast tumor specimens, 7 (64%) were also positive for EBV DNA in the peripheral blood, while 4 (36%) were positive for EBV DNA in the tumor, but negative in the blood. EBV was found at extremely low levels, with a mean of 0.00004 EBV genomes per cell (range 0.00014 to 0.00001 EBV genomes per cell). Furthermore, our finding of the presence of EBV in the tumor specimens coupled to the absence of detection of EBV genomic DNA in the peripheral blood is consistent with the epithelial nature of the virus. Because of the low levels of viral DNA in tumor tissue, further studies are needed to assess the biological input of EBV in breast cancer.
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- 2006
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45. Fructose-responsive genes in the small intestine of neonatal rats
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Cui, Xue-Lin, Soteropoulos, Patricia, Tolias, Peter, and Ferraris, Ronaldo P.
- Abstract
The intestinal brush border fructose transporter GLUT5 (SLC2A5) typically appears in rats after weaning is completed. However, precocious consumption of dietary fructose or in vivo perfusion for 4 h of the small intestine with high fructose (HF) specifically stimulates de novo synthesis of GLUT5 mRNA and protein before weaning is completed. Intermediary signals linking the substrate, fructose, to GLUT5 transcription are not known but should also respond to fructose perfusion. Hence, we used microarray hybridization and RT-PCR to identify genes whose expression levels change during HF relative to high-glucose (HG) perfusion. Expression of GLUT5 and NaPi2b, the intestinal Na+-dependent phosphate transporter, dramatically increased and decreased, respectively, with HF perfusion for 4 h. Expression of >20 genes, including two key gluconeogenic enzymes, glucose-6-phosphatase (G6P) and fructose-1,6-bisphosphatase, also increased markedly, along with fructose-2,6-bisphosphatase, an enzyme unique to fructose metabolism and regulating fructose-1,6-bisphosphatase activity. GLUT5 and G6P mRNA abundance, which increased dramatically with HF relative to HG, α-methylglucose, and normal Ringer perfusion, may be tightly and specifically linked to changes in intestinal luminal fructose but not glucose concentrations. G6P but not GLUT5 mRNA abundance increased after just 20 min of HF perfusion. This cluster of gluconeogenic enzymes and their common metabolic intermediate fructose-6-phosphate may regulate fructose metabolism and GLUT5 expression in the small intestine.
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- 2004
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46. In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat.
- Author
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Rong, Hu, Vidya, Hebbar, Bok-Ryang, Kim, Chi, Chen, Bozena, Winnik, Brian, Buckley, Patricia, Soteropoulos, Peter, Tolias, P, Hart Ronald, and Tony, Kong A-N
- Abstract
Sulforaphane (SUL) is one member of the isothiocyanate class of cancer chemopreventive compounds that has been shown to be effective in blocking initiation and progression of carcinogenesis. Previously, many studies have shown that SUL can potently induce phase II detoxifying enzymes, which contributes to its chemopreventive functions. In this study, we used 4967 oligonucleotides microarray to assess the genes that are modulated by SUL in in vivo rat livers, as well as time course of expression of these genes. The pharmacokinetics of SUL was assessed after oral dose of 50 micromol of SUL. The plasma concentration occurred at 1 h and peaked around 20 microM at 4 h after dosing and declined with a half-life of about 2.2 h. Analysis of the gene expression data found various clusters of genes that are important in cellular defense mechanisms and cell cycle regulation. The most robust cluster of genes is the metallothionein-like genes (MT-1/2 and MT-1a), which are increased up to 10-fold by 2 to 4 h after SUL dosing. The second cluster of genes is the glutathione S-transferase-A3-like genes, which include aflatoxin B1 aldehyde reductase and aldehyde oxidase. These genes are increased slightly by 4 h and peaked at 12 h. Real-time polymerase chain reaction was performed to authenticate the mRNA expression of some of these genes. In summary, this in vivo study of SUL provides the first clue as to the plasma concentrations of SUL, in vivo mitogen-activated protein kinase activations in rat livers, as well as what other genes are modulated in addition to phase II detoxifying genes. The results from this study may yield better insights for its chemopreventive functions.
- Published
- 2004
47. Functional cloning, sorting, and expression profiling of nucleic acid-binding proteins.
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Ramanathan, Y, Zhang, Haibo, Aris, Virginie, Soteropoulos, Patricia, Aaronson, Stuart A, and Tolias, Peter P
- Abstract
A major challenge in the post-sequencing era is to elucidate the activity and biological function of genes that reside in the human genome. An important subset includes genes that encode proteins that regulate gene expression or maintain the structural integrity of the genome. Using a novel oligonucleotide-binding substrate as bait, we show the feasibility of a modified functional expression-cloning strategy to identify human cDNAs that encode a spectrum of nucleic acid-binding proteins (NBPs). Approximately 170 cDNAs were identified from screening phage libraries derived from a human colorectal adenocarcinoma cell line and from noncancerous fetal lung tissue. Sequence analysis confirmed that virtually every clone contained a known DNA- or RNA-binding motif. We also report on a complementary sorting strategy that, in the absence of subcloning and protein purification, can distinguish different classes of NBPs according to their particular binding properties. To extend our functional annotation of NBPs, we have used GeneChip expression profiling of 14 different breast-derived cell lines to examine the relative transcriptional activity of genes identified in our screen and cluster analysis to discover other genes that have similar expression patterns. Finally, we present strategies to analyze the upstream regulatory region of each gene within a cluster group and select unique combinations of transcription factor binding sites that may be responsible for dictating the observed synexpression.
- Published
- 2002
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48. Molecular Evaluation of the Plasma Membrane Proton Pump from Aspergillus fumigatus
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Burghoorn, Henriette P., Soteropoulos, Patricia, Paderu, Padmaja, Kashiwazaki, Ryota, and Perlin, David S.
- Abstract
ABSTRACTThe gene encoding the plasma membrane proton pump (H+-ATPase) of Aspergillus fumigatus, PMA1, was characterized from A. fumigatusstrain NIH 5233 and clinical isolate H11-20. An open reading frame of 3,109 nucleotides with two introns near the N terminus predicts a protein consisting of 989 amino acids with a molecular mass of approximately 108 kDa. The predicted A. fumigatusenzyme is 89 and 51% identical to H+- ATPases of Aspergillus nidulansand Saccharomyces cerevisiae, respectively. The A. fumigatus PMA1is a typical member of the P-type ATPase family that contains 10 predicted transmembrane segments and conserved sequence motifs TGES, CSDKTGT, MLTGD, and GDGVN within the catalytic region. The enzyme represents 2% of the total plasma membrane protein, and it is characteristically inhibited by orthovanadate, with a 50% inhibitory concentration of ∼1.8 μM. H+-ATPases from Aspergillusspp. contain a highly acidic insertion region of 60 amino acids between transmembrane segments 2 and 3, which was confirmed for the membrane-assembled enzyme with a peptide-derived antibody. An increasing A. fumigatus PMA1copy number confers enhanced growth in low-pH medium, consistent with its role as a proton pump. These results provide support for the development of the A. fumigatusH+-ATPase as a potential drug discovery target.
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- 2002
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49. Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss
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CARMEL, JASON B., GALANTE, ANTHONY, SOTEROPOULOS, PATRICIA, TOLIAS, PETER, RECCE, MICHAEL, YOUNG, WISE, and HART, RONALD P.
- Abstract
We have completed the first large-scale gene expression study of acute spinal cord injury (SCI) in rat. Oligonucleotide microarrays containing 1,200 gene-specific probes were used to quantify mRNA levels, relative to uninjured controls, in spinal cords injured using a standard contusion model. Our results revealed a marked loss of neuron-specific mRNAs at the injury site. The surviving cells showed a characteristic inflammatory response that started at the injury site and spread to the distal cord. Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord. Notably, phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly. Other mRNAs clustered temporally and spatially with these regeneration-associated genes. Thus we have described global patterns of gene expression following acute SCI, and we have identified targets for future study and possible therapeutic intervention.
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- 2001
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50. Helical Stalk Segments S4 and S5 of the Plasma Membrane H+-ATPase from Saccharomyces cerevisiaeAre Optimized to Impact Catalytic Site Environment*
- Author
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Soteropoulos, Patricia, Valiakhmetov, Airat, Kashiwazaki, Ryota, and Perlin, David S.
- Abstract
The stalk segments of P-type ion-translocating enzymes are presumed to play important roles in energy coupling. In this work, stalk segments S4 and S5 of the yeast H+-ATPase were examined for helical character, optimal length, and segment orientation by a combination of proline substitution, insertion/deletion mutagenesis, and second-site suppressor analyses. The substitution of various residues for helix-disrupting proline in both S4 (L353P,L353G; A354P; and G371P) and S5 (D676P and I684P) resulted in highly defective or inactive enzymes supporting the importance of helical character and/or the maintenance of essential interactions. The contiguous helical nature of transmembrane segment M5 and stalk element S5 was explored and found to be favorable, although not essential. The deletion or addition of one or more amino acids at positions Ala354in S4 and Asp676in S5, which were intended to either rotate helical faces or extend/reduce the length of helical segments, resulted in enzyme destabilization that abolished most enzyme assembly. Second-site suppressor mutations were obtained to primary site mutations G371A (S4) and D676G (S5) and were analyzed with a molecular structure model of the H+-ATPase. Primary site mutations were predicted to alter the site of phosphorylation either directly or indirectly. The suppressor mutations either directly changed packing around the primary site or altered the environment of the site of phosphorylation. Overall, these data support the view that stalk segments S4 and S5 of the H+-ATPase are helical elements that are optimized for length and interactions with other stalk elements and can influence the phosphorylation domain.
- Published
- 2001
- Full Text
- View/download PDF
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