University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

An essential role of the JAK-STAT pathway in ischemic preconditioning.

Abstract: The goal of this study was to determine the role of the Janus tyrosine kinase (JAK)–signal transducers and activators of transcription (STAT) pathway in the late phase of ischemic preconditioning (PC). A total of 230 mice were used. At 5 min after ischemic PC (induced with six cycles of 4-min coronary occlusion/4-min reperfusion), immunoprecipitation with anti-phosphotyrosine (anti-pTyr) antibodies followed by immunoblotting with anti-JAK antibodies revealed increased tyrosine phosphorylation of JAK1 (+257 ± 53%) and JAK2 (+238 ± 35%), indicating rapid activation of these two kinases. Similar results were obtained by immunoblotting with anti-pTyr-JAK1 and anti-pTyr-JAK2 antibodies. Western analysis with anti-pTyr-STAT antibodies demonstrated a marked increase in nuclear pTyr-STAT1 (+301 ± 61%) and pTyr-STAT3 (+253 ± 60%) 30 min after ischemic PC, which was associated with redistribution of STAT1 and STAT3 from the cytosolic to the nuclear fraction and with an increase in STAT1 and STAT3 γ-IFN activation site DNA-binding activity (+606 ± 64%), indicating activation of STAT1 and STAT3. No nuclear translocation or tyrosine phosphorylation of STAT2, STAT4, STAT5A, STAT5B, or STAT6 was observed. Pretreatment with the JAK inhibitor AG-490 20 min before the six occlusion/reperfusion cycles blocked the enhanced tyrosine phosphorylation of JAK1 and JAK2 and the increased tyrosine phosphorylation, nuclear translocation, and enhanced DNA-binding activity of STAT1 and STAT3. The same dose of AG-490 abrogated the protection against myocardial infarction and the concomitant up-regulation of inducible NO synthase (iNOS) protein and activity observed 24 h after ischemic PC. Taken together, these results demonstrate that ischemic PC induces isoform-selective activation of JAK1, JAK2, STAT1, and STAT3, and that ablation of this response impedes the up-regulation of iNOS and the concurrent acquisition of ischemic tolerance. This study demonstrates that the JAK-STAT pathway plays an essential role in the development of late PC. The results reveal a signaling mechanism that underlies the transcriptional up-regulation of the cardiac iNOS gene and the adaptation of the heart to ischemic stress.

Stromal Cell–Derived Factor-1α Confers Protection Against Myocardial Ischemia/Reperfusion Injury Role of the Cardiac Stromal Cell–Derived Factor-1α–CXCR4 Axis

Abstract: Background— Stromal cell–derived factor-1α (SDF-1α) binding to its cognate receptor, CXCR4, regulates a variety of cellular functions such as stem cell homing, trafficking, and differentiation. However, the role of the SDF-1α–CXCR4 axis in modulating myocardial ischemia/reperfusion injury is unknown. Methods and Results— In mice subjected to ischemic preconditioning, myocardial SDF-1α mRNA was found to be increased 3 hours later (P<0.05). Myocardial SDF-1α and CXCR4 mRNA and protein were found to be expressed in both cardiac myocytes and fibroblasts. SDF-1α production increased significantly after 1 or 4 hours of hypoxia and 18 hours of reoxygenation in cultured myocytes (P<0.05) but did not change in fibroblast cultures. In isolated myocytes, CXCR4 activation by SDF-1α resulted in increased phosphorylation of both ERK 1/2 and AKT and decreased phosphorylation of JNK and p38. Cultured myocytes pretreated with SDF-1α were resistant to hypoxia/reoxygenation damage, exhibiting less lactate dehydrogenase rele...

AstroImageJ: Image Processing and Photometric Extraction for Ultra-precise Astronomical Light Curves

Abstract: ImageJ is a graphical user interface (GUI) driven, public domain, Java-based, software package for general image processing traditionally used mainly in life sciences fields. The image processing capabilities of ImageJ are useful and extendable to other scientific fields. Here we present AstroImageJ (AIJ), which provides an astronomy specific image display environment and tools for astronomy specific image calibration and data reduction. Although AIJ maintains the general purpose image processing capabilities of ImageJ, AIJ is streamlined for time-series differential photometry, light curve detrending and fitting, and light curve plotting, especially for applications requiring ultra-precise light curves (e.g., exoplanet transits). AIJ reads and writes standard Flexible Image Transport System (FITS) files, as well as other common image formats, provides FITS header viewing and editing, and is World Coordinate System aware, including an automated interface to the astrometry.net web portal for plate solving images. AIJ provides research grade image calibration and analysis tools with a GUI driven approach, and easily installed cross-platform compatibility. It enables new users, even at the level of undergraduate student, high school student, or amateur astronomer, to quickly start processing, modeling, and plotting astronomical image data with one tightly integrated software package.

Lactate: The Ultimate Cerebral Oxidative Energy Substrate?:

Abstract: Research over the past two decades has renewed the interest in lactate, no longer as a useless end product of anaerobic glycolysis in brain (and other tissues), but as an oxidative substrate for energy metabolism. While this topic would be considered blasphemy only three decades ago, much recent evidence indicates that lactate does play a major role in aerobic energy metabolism in the brain, the heart, skeletal muscle, and possibly in any other tissue and organ. Nevertheless, this concept has challenged the old dogma and ignited a fierce debate, especially among neuroscientists, pitting the supporters of glucose as the major oxidative energy substrate against those who support lactate as a possible alternative to glucose under certain conditions. Meanwhile, researchers working on energy metabolism in skeletal muscle have taken great strides toward bridging between these two extreme positions, while avoiding the high decibels of an emotional debate. Employing their findings along with the existing old and new data on cerebral energy metabolism, it is postulated here that lactate is the only major product of cerebral (and other tissues) glycolysis, whether aerobic or anaerobic, neuronal or astrocytic, under rest or during activation. Consequently, this postulate entails that lactate is a major, if not the only, substrate for the mitochondrial tricarboxylic acid cycle. If proven true, this hypothesis could provide better understanding of the biochemistry and physiology of (cerebral) energy metabolism, while holding important implications in the field of neuroimaging. Concomitantly, it could satisfy both 'glucoseniks' and 'lactatians' in the ongoing debate.

Impediments to wound healing

Abstract: Chronic wounds will often heal in a short period of time if factors that inhibit wound healing are identified and managed. Recombinant growth factor therapy may provide an added stimulus to healing in certain types of chronic wounds. However, there remains no substitute for a physiologic environment conducive to tissue repair and regeneration, without which the efficacy of growth factor therapy is questionable. Some of the most commonly encountered and clinically significant impediments to wound healing include wound hypoxia, infection, presence of debris and necrotic tissue, use of anti-inflammatory medications, a diet deficient in vitamins or minerals, or general nutritional deficiencies, tumors, environmental factors, and metabolic disorders, such as diabetes mellitus. Treatment of chronic wounds should be directed against the main etiologic factors responsible for the wound. Moreover, factors that may impede healing must be identified and, if possible, corrected, for healing to occur.