99mTc-interleukin-2 scintigraphy in normal subjects and in patients with autoimmune thyroid diseases: a feasibility study

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Prevention of diabetic nephropathy in Ins2+/−AkitaJ mice by the mitochondria-targeted therapy MitoQ

Mitochondrial production of ROS (reactive oxygen species) is thought to be associated with the cellular damage resulting from chronic exposure to high glucose in long-term diabetic patients. We hypothesized that a mitochondria-targeted antioxidant would prevent kidney damage in the Ins2+/−AkitaJ mouse model (Akita mice) of Type 1 diabetes. To test this we orally administered a mitochondria-targeted ubiquinone (MitoQ) over a 12-week period and assessed tubular and glomerular function. Fibrosis and pro-fibrotic signalling pathways were determined by immunohistochemical analysis, and mitochondria were isolated from the kidney for functional assessment. MitoQ treatment improved tubular and glomerular function in the Ins2+/−AkitaJ mice. MitoQ did not have a significant effect on plasma creatinine levels, but decreased urinary albumin levels to the same level as non-diabetic controls. Consistent with previous studies, renal mitochondrial function showed no significant change between any of the diabetic or wild-type groups. Importantly, interstitial fibrosis and glomerular damage were significantly reduced in the treated animals. The pro-fibrotic transcription factors phospho-Smad2/3 and β-catenin showed a nuclear accumulation in the Ins2+/−AkitaJ mice, which was prevented by MitoQ treatment. These results support the hypothesis that mitochondrially targeted therapies may be beneficial in the treatment of diabetic nephropathy. They also highlight a relatively unexplored aspect of mitochondrial ROS signalling in the control of fibrosis

Электроимпульсное плазменное спекания светопропускающей керамики на основе оксида алюминия

Объектом исследования является: нанопорошок оксида алюминия Al2O3, светопропускающая керамика на основе ?-Al2O3, которая была изготовлена методом электроимпульсного плазменного спекания. Цель работы – изготовление светопропускающей керамики на основе альфа оксида алюминия методом электроимпульсного плазменного спекания (ЭИПС) и исследование оптических свойств полученной керамики. В настоящей работе представлен аналитический обзор научных публикаций посвящённых получению светопропускающей керамики на основе оксида алюминия. Проведена характеризация исходных порошков оксида алюминия, изучены их морфологические и структурные характеристики. Керамические образцы изготовлены методом электроимпульсного плазменного спекания, изучены их оптические свойства.The object of study: nanopowder aluminum oxide Al2O3, translucent ceramics based on ?-Al2O3, which was produced by spark plasma sintering. The purpose of the work is the manufacture of translucent ceramics based on alpha aluminum oxide by the method of spark plasma sintering (SPS) and the study of the optical properties of the obtained ceramics. This paper presents an analytical review of scientific publications devoted to the production of translucent ceramics based on aluminum oxide. The initial aluminium oxide powders have been characterized, their morphological and structural characteristics have been investigated. Ceramic samples were synthesized by spark plasma sintering and their optical properties of sintered ceramic samples were investigated

Common Learning Every Day: The American Heritage of Popular (Public and Private P-12) Schooling

When it comes to P-12 education, we all have a story, or many stories. We spend almost half of our childhood and adolescent days in schools, most but not all of us in public schools. Not only do we have our own stories, but public (and private) schooling in America has its own story, a heritage of sorts, though one with many strands. The American educational heritage is linked to the preparation of democratic citizens, so its historic successes and failures are of paramount importance. We will tell some shared and/or distinct stories about American education writ large, and solicit your responses as well as the stories you can tell about your 13 or so years in pre-collegiate education

Structure and Dynamics of Telomerase

Telomeres are repetitive, G-rich DNA sequences, along with DNA-associated proteins, that cap the ends of linear chromosomes. Telomeres serve a two-fold function; they protect the ends of chromosomes from being recognized as sites of DNA damage and they prevent fraying of chromosomes into coding regions during successive rounds of DNA replication. In proliferative cells where unregulated chromosome end shortening would be a critical problem, telomere lengths are maintained by the specialized reverse transcriptase enzyme, telomerase. Because of its requirement in proliferative cells, telomerase is also upregulated in about 90% of cancer, making it an attractive target for cancer therapeutics. Telomerase is a ribonucleoprotein, composed of a protein component, TERT, and an RNA component, TR. Telomerase reverse transcribes telomere repeats onto the 3’ end of chromosomes through its integral template within TR. Telomerase is unique among reverse transcriptases in that it is able to add multiple telomere repeats during a single binding event. The precise conformational rearrangements required for this processive telomerase action are not well understood. In this thesis, I focus on the interaction between telomerase and the nascent telomere and how reverse transcription of multiple repeats affects the actively extending telomerase complex. First, I focus on how template boundary definition ensures the faithful synthesis of the required hexameric telomere sequence and demonstrate that critical regions within both TERT and TR are responsible for establishing strict template boundary definition. Second, I focus on the interplay between DNA structure formation within the nascent telomere and the actively extending telomerase complex and show that formation of G-quadruplexes within the telomere sequence affects telomerase activity. Lastly, I discuss ongoing work using single molecule techniques to investigate dynamics of human telomerase during the telomerase catalytic cycle and the problems that must be overcome to complete this work

Advances in 99mTc-Labeling of Antibodies

Several methods have been developed to label antibodies with 99mTc. Direct labeling results in 99mTc binding to multiple sites of various affinities that are often weaker than the binding to strong chelating agents. Attempts to overcome this disadvantage involve conjugation of strong chelating agents to the antibodies. While stability is usually enhanced, this approach suffers from alteration of antibody properties as well as non-specific binding of 99mTc to the antibody instead of to the conjugated chelating agent. This has been of concern for studies with DTPA as the chelating agent. In this study the loss of 99mTc by N2S2 challenge shows that a fraction of the 99mTc is nonspecifically bound to the antibody. An advantage of the approach of labeling antibodies containing a bifunctional chelating agent is the simplicity of the labeling procedure and the apparent high yields that in reality are the sum of chelating agent and non-specifically bound radioactivity. The last approach described in our work of conjugation of a preformed chelate has advantages of characterizable 99mTc complex chemistry and conjugation by standard protein derivatiza- tion chemistry. Slow chelation kinetics can be overcome in the small molecule stage and then conjugation performed under mild conditions with respect to the antibody or fragments. This approach, however, suffers from greater complexity of the labeling process including multiple steps, purifications and non-quantitative yields. The use of ligands for 99mTc in which the complexes are of high stability and predictable chemistry is likely to result in eventual optima labeling technologies. Processes which are non-specific may work in some cases, but are likely to present difficulties in optimization and general applicability from antibody to antibody.</jats:p