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Full-Text Articles in Medicine and Health Sciences
Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén
Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén
Physiology Faculty Publications
AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).
METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …
Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito
Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito
Physiology Faculty Publications
Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …
Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus
Alzheimer's Disease Genetics And Abca7 Splicing, Jared B. Vasquez, James F. Simpson, Ryan Harpole, Steven Estus
Physiology Faculty Publications
Both common and rare polymorphisms within ABCA7 have been associated with Alzheimer’s disease (AD). In particular, the rare AD associated polymorphism rs200538373 was associated with altered ABCA7 exon 41 splicing and an AD risk odds ratio of ∼1.9. To probe the role of this polymorphism in ABCA7 splicing, we used minigene studies and qPCR of human brain RNA. We report aberrant ABCA7 exon 41 splicing in the brain of a carrier of the rs200538373 minor C allele. Moreover, minigene studies show that rs200538373 acts as a robust functional variant in vitro. Lastly, although the ABCA7 isoform with an extended …
Myocardial Relaxation Is Accelerated By Fast Stretch, Not Reduced Afterload, Charles S. Chung, Charles W. Hoopes, Kenneth S. Campbell
Myocardial Relaxation Is Accelerated By Fast Stretch, Not Reduced Afterload, Charles S. Chung, Charles W. Hoopes, Kenneth S. Campbell
Physiology Faculty Publications
Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the …
Myonuclear Transcription Is Responsive To Mechanical Load And Dna Content But Uncoupled From Cell Size During Hypertrophy, Tyler J. Kirby, Rooshil M. Patel, Timothy S. Mcclintock, Esther E. Dupont-Versteegden, Charlotte A. Peterson, John J. Mccarthy
Myonuclear Transcription Is Responsive To Mechanical Load And Dna Content But Uncoupled From Cell Size During Hypertrophy, Tyler J. Kirby, Rooshil M. Patel, Timothy S. Mcclintock, Esther E. Dupont-Versteegden, Charlotte A. Peterson, John J. Mccarthy
Physiology Faculty Publications
Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number …
Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian
Characterization Of Secretory Sphingomyelinase Activity, Lipoprotein Sphingolipid Content And Ldl Aggregation In Ldlr-/- Mice Fed On A High-Fat Diet, Gergana M. Deevska, Manjula Sunkara, Andrew J. Morris, Mariana N. Nikolova‑Karakashian
Physiology Faculty Publications
The propensity of LDLs (low-density lipoproteins) for aggregation and/or oxidation has been linked to their sphingolipid content, specifically the levels of SM (sphingomyelin) and ceramide. To investigate this association in vivo, ldlr (LDL receptor)-null mice (ldlr-/-) were fed on a modified (atherogenic) diet containing saturated fats and cholesterol. The diet led to significantly elevated SM content in all serum lipoproteins. In contrast, ceramide increased only in the LDL particles. MS-based analyses of the lipid acyl chain composition revealed a marked elevation in C16:0 fatty acid in SM and ceramide, consistent with the prevalence of palmitic acid in the modified diet. …
Atovaquone Ameliorate Gastrointestinal Toxoplasmosis Complications In A Pregnancy Model, Helieh S. Oz, Thomas Tobin
Atovaquone Ameliorate Gastrointestinal Toxoplasmosis Complications In A Pregnancy Model, Helieh S. Oz, Thomas Tobin
Physiology Faculty Publications
Background: Toxoplasma is an important source of foodborne hospitalization with no safe and effective therapy against chronic or congenital Toxopalsmosis. Atovaquone is a drug of choice but not approved for use in congenital Toxoplasmosis. We hypothesized atovaquone to be safe and effective against feto-maternal Toxoplasmosis.
Material/Methods: Programmed pregnant mice were i.p. infected with 50–2400 Tachyzoites from Type II strain (clone PTG). Dams were treated daily with atovaquone or sham and monitored for pain, and complications.
Results: Dams developed pain related abdominal hypersensitivity (allodynia) to mechanical stimuli in a Tachyzoites dose dependent manner. Infected dams were anemic and exhibited ascities and …