University of Pittsburgh

About: University of Pittsburgh is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 87042 authors who have published 201012 publications receiving 9656783 citations. The organization is also known as: Pitt & Western University of Pennsylvania.

The Evolutionary Enigma of Mixed Mating Systems in Plants: Occurrence, Theoretical Explanations, and Empirical Evidence

Abstract: ▪ Abstract Mixed mating, in which hermaphrodite plant species reproduce by both self- and cross-fertilization, presents a challenging problem for evolutionary biologists. Theory suggests that inbreeding depression, the main selective factor opposing the evolution of selfing, can be purged with self-fertilization, a process that is expected to yield pure strategies of either outcrossing or selfing. Here we present updated evidence suggesting that mixed mating systems are frequent in seed plants. We outline the floral and pollination mechanisms that can lead to intermediate outcrossing, review the theoretical models that address the stability of intermediate outcrossing, and examine relevant empirical evidence. A comparative analysis of estimated inbreeding coefficients and outcrossing rates suggests that mixed mating often evolves despite strong inbreeding depression. The adaptive significance of mixed mating has yet to be fully explained for any species. Recent theoretical and empirical work suggests that...

Synthesis and evaluation of 11c-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents

Abstract: The synthesis and evaluation of a series of neutral analogues of thioflavin-T (termed BTA's) with high affinities for aggregated amyloid and a wide range of lipophilicities are reported Radiolabeling with high specific activity [(11)C]methyl iodide provided derivatives for in vivo evaluation Brain entry in control mice and baboons was high for nearly all of the analogues at early times after injection, but the clearance rate of radioactivity from brain tissue varied by more than 1 order of magnitude Upon the basis of its rapid clearance from normal mouse and baboon brain tissues, [N-methyl-(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [(11)C]6-OH-BTA-1) was selected as the lead compound for further evaluation The radiolabeled metabolites of [(11)C]6-OH-BTA-1 were polar and did not enter brain The binding affinities of [N-methyl-(3)H]6-OH-BTA-1 for homogenates of postmortem AD frontal cortex and synthetic Abeta(1-40) fibrils were similar (K(d) = 14 nM and 47 nM, respectively), but the ligand-to-Abeta peptide binding stoichiometry was approximately 400-fold higher for AD brain than Abeta(1-40) fibrils Staining of AD frontal cortex tissue sections with 6-OH-BTA-1 indicated the selective binding of the compound to amyloid plaques and cerebrovascular amyloid The encouraging in vitro and in vivo properties of [(11)C]6-OH-BTA-1 support the choice of this derivative for further evaluation in human subject studies of brain Abeta deposition

Sickle Cell Disease

Abstract: Sickle-cell disease is one of the most common severe monogenic disorders in the world. Haemoglobin polymerisation, leading to erythrocyte rigidity and vaso-occlusion, is central to the pathophysiology of this disease, although the importance of chronic anaemia, haemolysis, and vasculopathy has been established. Clinical management is basic and few treatments have a robust evidence base. One of the main problems of sickle-cell disease in children is the development of cerebrovascular disease and cognitive impairment, and the role of blood transfusion and hydroxycarbamide for prevention of these complications is starting to be understood. Recurrent episodes of vaso-occlusion and inflammation result in progressive damage to most organs, including the brain, kidneys, lungs, bones, and cardiovascular system, which becomes apparent with increasing age. Most people with sickle-cell disease live in Africa, where little is known about this disease; however, we do know that the disorder follows a more severe clinical course in Africa than for the rest of the world and that infectious diseases have a role in causing this increased severity of sickle-cell disease. More work is needed to develop effective treatments that specifically target pathophysiological changes and clinical complications of sickle-cell disease.

Gene therapy progress and prospects: nonviral vectors.

Abstract: The success of gene therapy is largely dependent on the development of the gene delivery vector. Recently, gene transfection into target cells using naked DNA, which is a simple and safe approach, has been improved by combining several physical techniques, for example, electroporation, gene gun, ultrasound and hydrodynamic pressure. Chemical approaches have been utilized to improve the efficiency and cell specificity of gene transfer. Novel gene carrier molecules, which facilitate DNA escape from the endosome into the cytosol, have been developed. Several functional polymers, which enable controlled release of DNA in response to an environmental change, have also been reported. Plasmids with reduced number of CpG motifs, the use of PCR fragments and the sequential injection method have been established for the reduction of immune response triggered by plasmid DNA. Construction of a long-lasting gene expression system is also an important theme for nonviral gene therapy. To date, tissue-specific expression, self-replicating and integrating plasmid systems have been reported. Improvement of delivery methods together with intelligent design of the DNA itself has brought about large degrees of enhancement in the efficiency, specificity and temporal control of nonviral vectors.