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.

Dopaminergic nigrostriatal projections regulate neural precursor proliferation in the adult mouse subventricular zone.

Abstract: An understanding of the regulators of neurogenesis in the normal and diseased brain is necessary in order to recruit endogenously produced neural precursors for cell replacement in neurodegenerative disorders such as Parkinson's disease. The location of dopaminergic projections from the midbrain to the neostriatum and nucleus accumbens overlaps with the most active region of neurogenesis in the adult brain, the subventricular zone of the anterior lateral ventricle. This suggests that dopamine may contribute to regulation of the subventricular niche of adult neurogenesis. Here, we show in adult mice that destruction of the dopaminergic neurons in the substantia nigra and ventral tegmental area in a 6-hydroxydopamine model of Parkinson's disease reduced the number of proliferating neural precursors in the subventricular zone of the anterior lateral ventricle by approximately 40%. The effect on neural precursor proliferation correlated with the extent of dopaminergic denervation in the neighboring neostriatum. This identifies dopamine as one of the few known endogenous regulators of adult neurogenesis with implications for the potential use of endogenous neural precursors in cell replacement strategies for Parkinson's disease.

Spreading speeds as slowest wave speeds for cooperative systems.

Abstract: It is well known that in many scalar models for the spread of a fitter phenotype or species into the territory of a less fit one, the asymptotic spreading speed can be characterized as the lowest speed of a suitable family of traveling waves of the model. Despite a general belief that multi-species (vector) models have the same property, we are unaware of any proof to support this belief. The present work establishes this result for a class of multi-species model of a kind studied by Lui [Biological growth and spread modeled by systems of recursions. I: Mathematical theory, Math. Biosci. 93 (1989) 269] and generalized by the authors [Weinberger et al., Analysis of the linear conjecture for spread in cooperative models, J. Math. Biol. 45 (2002) 183; Lewis et al., Spreading speeds and the linear conjecture for two-species competition models, J. Math. Biol. 45 (2002) 219]. Lui showed the existence of a single spreading speed c ∗ for all species. For the systems in the two aforementioned studies by the authors, which include related continuous-time models such as reaction-diffusion systems, as well as some standard competition models, it sometimes happens that different species spread at different rates, so that there are a slowest speed c ∗ and a fastest speed c f ∗ . It is shown here that, for a large class of such multi-species systems, the slowest spreading speed c ∗ is always characterized as the slowest speed of a class of traveling wave solutions.

Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis

Abstract: Mixed lineage kinase domain-like pseudokinase (MLKL) mediates necroptosis by translocating to the plasma membrane and inducing its rupture. The activation of MLKL occurs in a multimolecular complex (the 'necrosome'), which is comprised of MLKL, receptor-interacting serine/threonine kinase (RIPK)-3 (RIPK3) and, in some cases, RIPK1. Within this complex, RIPK3 phosphorylates the activation loop of MLKL, promoting conformational changes and allowing the formation of MLKL oligomers, which migrate to the plasma membrane. Previous studies suggested that RIPK3 could phosphorylate the murine MLKL activation loop at Ser345, Ser347 and Thr349. Moreover, substitution of the Ser345 for an aspartic acid creates a constitutively active MLKL, independent of RIPK3 function. Here we examine the role of each of these residues and found that the phosphorylation of Ser345 is critical for RIPK3-mediated necroptosis, Ser347 has a minor accessory role and Thr349 seems to be irrelevant. We generated a specific monoclonal antibody to detect phospho-Ser345 in murine cells. Using this antibody, a series of MLKL mutants and a novel RIPK3 inhibitor, we demonstrate that the phosphorylation of Ser345 is not required for the interaction between RIPK3 and MLKL in the necrosome, but is essential for MLKL translocation, accumulation in the plasma membrane, and consequent necroptosis.

Multipractice analysis of laparoscopic cholecystectomy in 1,983 patients☆

Abstract: We analyzed the results of laparoscopic cholecystectomy in 1,983 patients from a variety of practice settings in order to evaluate a large, cross-sectional experience for this new procedure. Twenty general surgeons from 9 clinics in 4 states examined the records and outcome of their laparoscopic cholecystectomy patients through March 1991. In 88 patients (4.5%), the operation was converted to an open procedure, usually because of marked inflammation and unclear anatomy. A total of 644 cases were performed with laser dissection and 1,339 with cautery, and the results of these 2 methods were similar. There were 41 complications. Reoperation for repair was necessary in 18 patients, including 5 with common duct injuries, and, to date, the outcome has been good in each patient. Seventy-six patients (3.8%) have had recognized common duct stones; these were removed preoperatively by endoscopic sphincterotomy (ERS) in 20 patients, during cholecystectomy in 46 patients, and postoperatively by ERS in 4 patients. In six patients, common duct stones became apparent 1 to 4 months after cholecystectomy. We conclude that trained general surgeons can perform laparoscopic cholecystectomy safely with risks comparable to those for conventional open cholecystectomy.