23 research outputs found
Part 2 of Age-related proteostatic imbalance exacerbates heart failure with preserved ejection fraction pathogenesis in old mice
No full text<p>Heart failure with preserved ejection fraction (HFpEF) is a leading cause of hospitalization and death in the elderly. While aging strongly increases the incidence of HFpEF, the specific influences of aging on HFpEF at molecular and pathophysiological levels remain unclear. Here, we show that aged mice, when subjected to chronic metabolic and hypertensive stress (2-hit stress), develop an aggravated cardiometabolic HFpEF phenotype compared to younger counterparts. Aged HFpEF mice also display unique pathological characteristics reminiscent of those found in HFpEF patients. We demonstrate that age-related dysfunction in protein quality control (PQC) exacerbates proteostatic stress in HFpEF. Specifically, we demonstrate that increased protein synthesis induced by 2-hit stress combines with age-related impairment in protein degradation in aged HFpEF hearts, culminating in the accumulation of protein aggregates. These findings underscore the importance of incorporating aging into preclinical HFpEF models and support the therapeutic potentials of targeting PQC mechanisms to ameliorate disease outcomes.</p>
<p>The deposited data are lc-ms data acquired on the Thermo QEx-Plus system. For any questions, please contact mike kinter mike-kinter at omrf.org</p>
<p>This upload contains the second part of the data. The majority of the data and a complete list of authors can be found in 10.5281/zenodo.10993216</p>
Age-related proteostatic imbalance exacerbates heart failure with preserved ejection fraction pathogenesis in old mice
No full text<p>Heart failure with preserved ejection fraction (HFpEF) is a leading cause of hospitalization and death in the elderly. While aging strongly increases the incidence of HFpEF, the specific influences of aging on HFpEF at molecular and pathophysiological levels remain unclear. Here, we show that aged mice, when subjected to chronic metabolic and hypertensive stress (2-hit stress), develop an aggravated cardiometabolic HFpEF phenotype compared to younger counterparts. Aged HFpEF mice also display unique pathological characteristics reminiscent of those found in HFpEF patients. We demonstrate that age-related dysfunction in protein quality control (PQC) exacerbates proteostatic stress in HFpEF. Specifically, we demonstrate that increased protein synthesis induced by 2-hit stress combines with age-related impairment in protein degradation in aged HFpEF hearts, culminating in the accumulation of protein aggregates. These findings underscore the importance of incorporating aging into preclinical HFpEF models and support the therapeutic potentials of targeting PQC mechanisms to ameliorate disease outcomes.</p>
<p>The deposited data are lc-ms data acquired on the Thermo QEx-Plus system. For any questions, please contact mike kinter mike-kinter at omrf.org</p>
<p>This upload contains the bulk of the LC-MS data. But, due to file sizes, and addition group of files can be found at doi 10.5281/zenodo.11094720</p>
Current Trends in Income of Communications Enterprises
No full text Communications income shows more stability than national income, but costs appear to increase more rapidly than revenue in a boom and fall less in a depression. Author of several earlier articles * on this subject, Dr. Kinter is economist with a Chicago investment firm and lecturer on economics at Northwestern. </jats:p
Increased Cardiac PFK-2 Protects Against High-Fat Diet-Induced Cardiomyopathy and Mediates Beneficial Systemic Metabolic Effects
No full textAbstract. The healthy heart adapts to changes in nutrient availability and energy demands. In metabolic diseases like type 2 diabetes (T2D), increased reliance on fatty acids for energy production contributes to mitochondrial dysfunction and cardiomyopathy. A principal regulator of cardiac metabolism is 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2), which is a central driver of glycolysis. We hypothesized that increasing PFK-2 activity could mitigate cardiac dysfunction induced by high fat diet (HFD). Wild type (WT) and cardiac-specific transgenic mice expressing PFK-2 (GlycoHi) were fed a low fat or HFD for 16-weeks to induce metabolic dysfunction. Metabolic phenotypes were determined by measuring mitochondrial bioenergetics and performing targeted quantitative proteomic and metabolomic analysis. Increasing cardiac PFK-2 had beneficial effects on cardiac and mitochondrial function. Unexpectedly, GlycoHi mice also exhibited sex-dependent systemic protection from HFD, including increased glucose homeostasis. These findings support improving glycolysis via PFK-2 activity can mitigate mitochondrial and functional changes that occur with metabolic syndrome.
There are two types of data in this upload, proteomics and metabolomics.
The proteomics data are raw files acquired on a tsq quantiva triple quadrupole mass spectrometer in the SRM mode at OMRF. Each file is panel of protein assays. Please contact Mike Kinter with questions.
The metabolomics data are more processed data files as described in the paper. Please contact Haiwei Gu with questions
El Niño and the Southern Oscillation in Parameterized and Super-Parameterized Coupled General Circulation Models
No full textThe explicit treatment of cloud-scale processes in a super-parameterized coupled general circulation model (SP-CGCM) is known to produce improved total heating and low-level wind variability on interannual time scales relative to a model with conventional parameterization of convection. In this study, a novel linear statistical adjustment method has been explored to introduce a state-dependent adjustment such that the dominant modes of variability in the model with the explicit treatment of clouds are captured in the conventional model. This method was applied to isolate and quantify the impact of the horizontal gradients and time evolution of the surface stress forcing of the ocean due to the interannual surface stress variability of the SP-CGCM. The usefulness of this approach in isolating the effects of equatorial and off-equatorial oceanic wave response to the interannual surface stress forcing is demonstrated.This work is embargoed by the author and will not be available until June 2014
Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina:insights into X-linked Retinitis Pigmentosa and associated ciliopathies
No full textMutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR 1-19 and RPGR ORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors
High-fat Diet Induced Cardiac Oxidative Stress Differentially Modulates Protein Expression and Specific Activity of the Antioxidant Enzyme Catalase
No full textIndependent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice
No full textObesity is one of the most significant risk factors for knee osteoarthritis. However, therapeutic strategies to prevent or treat obesity-associated osteoarthritis are limited because of uncertainty about the etiology of disease, particularly with regard to metabolic factors. High-fat-diet-induced obese mice have become a widely used model for testing hypotheses about how obesity increases the risk of osteoarthritis, but progress has been limited by variation in disease severity, with some reports concluding that dietary treatment alone is insufficient to induce osteoarthritis in mice. We hypothesized that increased sucrose content of typical low-fat control diets contributes to osteoarthritis pathology and thus alters outcomes when evaluating the effects of a high-fat diet. We tested this hypothesis in male C57BL/6J mice by comparing the effects of purified diets that independently varied sucrose or fat content from 6 to 26 weeks of age. Outcomes included osteoarthritis pathology, serum metabolites, and cartilage gene and protein changes associated with cellular metabolism and stress-response pathways. We found that the relative content of sucrose versus cornstarch in low-fat iso-caloric purified diets caused substantial differences in serum metabolites, joint pathology, and cartilage metabolic and stress-response pathways, despite no differences in body mass or body fat. We also found that higher dietary fat increased fatty acid metabolic enzymes in cartilage. The findings indicate that the choice of control diets should be carefully considered in mouse osteoarthritis studies. Our study also indicates that altered cartilage metabolism might be a contributing factor to how diet and obesity increase the risk of osteoarthritis
Final Report of the DAUFIN project
No full textDAUFIN = Data Assimulation within Unifying Framework for Improved river basiN modeling (EC 5th framework Project
The Simulated Indian Monsoon: A GCM Sensitivity Study
No full textThe authors find that the deficiency of the model precipitation simulation may be attributed to the use of an enhanced orography in the integrations. Replacement of this orography with a mean orography results in a much more realistic simulation of Indian monsoon circulation and rainfall. Experiments with a linear primitive equation model on the sphere suggest that this striking improvement is due to modulations of the orographically forced waves in the lower troposphere. This improvement in the monsoon simulation is due to the kinematic and dynamical effects of changing the topography, rather than the thermal effects, which were minimal. The magnitude of the impact on the Indian monsoon of the other sensitivity experiments varied considerably but was consistently less than the impact of using the mean orography. However, results from the soil moisture sensitivity experiments suggest a possibly important role for soil moisture in simulating tropical precipitation. -from Author
