N-Acetylaspartate Metabolism Outside the Brain: Lipogenesis, Histone Acetylation, and Cancer

N-acetylaspartate (NAA) is a highly abundant brain metabolite. Aberrant NAA concentrations have been detected in many pathological conditions and although the function of NAA has been extensively investigated in the brain it is still controversial. Only recently, a role of NAA has been reported outside the brain. In brown adipocytes, which show high expression of the NAA-producing and the NAA-cleaving enzyme, the metabolism of NAA has been implicated in lipid synthesis and histone acetylation. Increased expression of N-acetyltransferase 8-like (Nat8l, the gene encoding the NAA synthesizing enzyme) induces de novo lipogenesis and the brown adipocyte phenotype. Accordingly silencing of aspartoacylase, the NAA-cleaving enzyme, reduced brown adipocyte differentiation mechanistically by decreasing histone acetylation and gene transcription. Notably, the expression of Nat8l and the amount of NAA were also shown to be increased in several tumors and inversely correlate with patients’ survival. Additionally, Nat8l silencing reduced cell proliferation in tumor and non-tumor cells, while NAA supplementation could rescue it. However, the mechanism behind has not yet been clarified. It remains to be addressed whether NAA per se and/or its catabolism to acetate and aspartate, metabolites that have both been implicated in tumor growth, are valuable targets for future therapies

Advanced Denoising for X-ray Ptychography

The success of ptychographic imaging experiments strongly depends on achieving high signal-to-noise ratio. This is particularly important in nanoscale imaging experiments when diffraction signals are very weak and the experiments are accompanied by significant parasitic scattering (background), outliers or correlated noise sources. It is also critical when rare events such as cosmic rays, or bad frames caused by electronic glitches or shutter timing malfunction take place. In this paper, we propose a novel iterative algorithm with rigorous analysis that exploits the direct forward model for parasitic noise and sample smoothness to achieve a thorough characterization and removal of structured and random noise. We present a formal description of the proposed algorithm and prove its convergence under mild conditions. Numerical experiments from simulations and real data (both soft and hard X-ray beamlines) demonstrate that the proposed algorithms produce better results when compared to state-of-the-art methods.Comment: 24 pages, 9 figure

Verhalten funktionalisierter Nanopartikel an Grenzschichten mit Polymerbürsten

Die vorliegende Arbeit liefert einen Beitrag zum Verständnis der komplexen Wechselwirkungen zwischen Nanopartikeln und Polymeren in dünnen Schichtsystemen. Dazu wurden in einem geeignetem Modellsystem drei verschiedene Einflussparameter auf die Nanopartikelverteilung im Polymer und zwischen einer hydrophilen und einer hydrophoben Grenzfläche analysiert. Für eine erste Abschätzung der Verträglichkeit der einzelnen Komponenten wurden Wechselwirkungsparameter, binäre und ternäre Phasendiagramme ermittelt. Die experimentelle Charakterisierung der Nanopartikelverteilung erfolgte mittels Rasterkraftmikroskopie, Rasterelektronenmikroskopie und Transmissionselektronenmikroskopie. Die erhaltenen Ergebnisse wurden mit denen der theoretischen Vorbetrachtungen verglichen um herauszufinden, ob Vorhersagen zur Nanopartikelverteilung in einem Polymer möglich sind. In dieser Arbeit konnte gezeigt werden, dass die Nanopartikelverteilung im Polymer mit den untersuchten Parametern gezielt beeinflusst werden kann

Vestibular rehabilitation in elderly patients with benign paroxysmal positional vertigo

The Benign Paroxysmal Positional Vertigo (BPPV) is a vestibular disorder where the patients complain brief moments of vertigo and/or present postural instability, caused by a brusque change in the cephalic or body movement. AIM: The objective of the present study is certificate the benefit of the vestibular rehabilitation in elderly people with Benign Paroxysmal Positional Vertigo. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD: Sixteen patients with BPPV were thread with extract of Ginkgo-biloba (40mg of 12/12h) during 30 days. Eight patients (the Experimental Group) were submitted to vestibular rehabilitation and the other called Control Group, didn't perform any kind of exercises. In order to perform the evaluation of the benefit we used the Scale of Activity of Daily Life and Vestibular Disorders by Kohen and Kimball, and used the t-student test to statistical analysis. CONCLUSION: The vestibular rehabilitation in group showed benefit in the treatment in the Experimental Group; the Scale of Activity of Daily Life and Vestibular Disorders, was an important tool for the qualitative evaluation in our rehabilitation proposal and the vestibular rehabilitation in group showed as an excellent therapeutic strategy.A Vertigem Posicional Paroxística Benigna (VPPB) é um distúrbio vestibular no qual os pacientes relatam breves momentos de vertigem e/ou leve instabilidade postural, ocasionados por uma mudança brusca na movimentação cefálica ou corporal. OBJETIVO: Verificar o benefício da reabilitação vestibular, realizada em grupo, em pacientes idosos portadores de VPPB. FORMA DE ESTUDO: Clínico prospectivo. MATERIAL E MÉTODO: Foram selecionados aleatoriamente 16 pacientes portadores de VPPB, todos medicados com extrato de Gingko-biloba (40mg de 12/12h) durante 30 dias. Oito deles, que formaram o Grupo Experimental, além do medicamento, foram submetidos à reabilitação vestibular e oito compuseram o Grupo Controle que não realizaram nenhum tipo de exercício. Para avaliação do benefício aplicamos a Escala de Atividades de Vida Diária e Desordens Vestibulares proposta por Cohen e Kimball. Para a análise estatística utilizamos o teste t-student. CONCLUSÃO: Nossos resultados apontaram benefício promovido pela reabilitação vestibular em grupo no tratamento de idosos portadores de VPPB; a avaliação qualitativa mostrou-se instrumento importante para a avaliação de benefício para o tratamento proposto; e a reabilitação vestibular em grupo mostrou ser uma excelente estratégia terapêutica.UNIBANUMESPUNIFESP-EPMSanta Casa de São Paulo Faculdade de Ciências MédicasUNIFESP, EPMSciEL

Characterization of distinct subpopulations of hepatic macrophages in HFD/obese mice.

The current dogma is that obesity-associated hepatic inflammation is due to increased Kupffer cell (KC) activation. However, recruited hepatic macrophages (RHMs) were recently shown to represent a sizable liver macrophage population in the context of obesity. Therefore, we assessed whether KCs and RHMs, or both, represent the major liver inflammatory cell type in obesity. We used a combination of in vivo macrophage tracking methodologies and adoptive transfer techniques in which KCs and RHMs are differentially labeled with fluorescent markers. With these approaches, the inflammatory phenotype of these distinct macrophage populations was determined under lean and obese conditions. In vivo macrophage tracking revealed an approximately sixfold higher number of RHMs in obese mice than in lean mice, whereas the number of KCs was comparable. In addition, RHMs comprised smaller size and immature, monocyte-derived cells compared with KCs. Furthermore, RHMs from obese mice were more inflamed and expressed higher levels of tumor necrosis factor-α and interleukin-6 than RHMs from lean mice. A comparison of the MCP-1/C-C chemokine receptor type 2 (CCR2) chemokine system between the two cell types showed that the ligand (MCP-1) is more highly expressed in KCs than in RHMs, whereas CCR2 expression is approximately fivefold greater in RHMs. We conclude that KCs can participate in obesity-induced inflammation by causing the recruitment of RHMs, which are distinct from KCs and are not precursors to KCs. These RHMs then enhance the severity of obesity-induced inflammation and hepatic insulin resistance

Wind Power Persistence Characterized by Superstatistics

Mitigating climate change demands a transition towards renewable electricity generation, with wind power being a particularly promising technology. Long periods either of high or of low wind therefore essentially define the necessary amount of storage to balance the power system. While the general statistics of wind velocities have been studied extensively, persistence (waiting) time statistics of wind is far from well understood. Here, we investigate the statistics of both high- and low-wind persistence. We find heavy tails and explain them as a superposition of different wind conditions, requiring q-exponential distributions instead of exponential distributions. Persistent wind conditions are not necessarily caused by stationary atmospheric circulation patterns nor by recurring individual weather types but may emerge as a combination of multiple weather types and circulation patterns. This also leads to Fréchet instead of Gumbel extreme value statistics. Understanding wind persistence statistically and synoptically may help to ensure a reliable and economically feasible future energy system, which uses a high share of wind generation

Socialist Dandies International: East Europe, 1946-1959

This article maps the looks and lifestyle choices of small groups of young, like-minded people who emerged in the postwar Soviet Union and East Europe in the background of huge political, social, and cultural changes. With their androgynous bodies wrapped in drape jackets and narrow trousers, and their love of jazz and swing, these young men stood in a sharp contrast to the official ideology that promoted socialism as a new, pure, and highly rationalized project, its ideal robust and strong man, and its mass culture that insisted on educational and restrained forms of entertainment. Through the categories of dress, body, and big city, the article investigates the clashes, and the eventual truce, between the socialist streamlined and rationalized master narrative and the young dandies' fragmented and disordered narrative. The article argues that the socialist dandies were not politically minded, and that their challenge to the officially proclaimed values was informed by their adolescent recklessness and a general postwar desolation. They were declared state enemies because the socialist regimes did not allow for alternative types of modernity. Consequently, the authorities condemned the young dandies' looks and interests as cosmopolitan, because they originated in the West, and as artificial, since they belonged to the culture that had preceded a new socialist world

Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease

Chlamydiae replicate in a vacuole within epithelial cells and commonly induce cell damage and a deleterious inflammatory response of unknown molecular pathogenesis. The chlamydial protease-like activity factor (CPAF) translocates from the vacuole to the cytosol, where it cleaves several cellular proteins. CPAF is synthesized as an inactive precursor that is processed and activated during infection. Here, we show that CPAF can be activated in uninfected cells by experimentally induced oligomerization, reminiscent of the activation mode of initiator caspases. CPAF activity induces proteolysis of cellular substrates including two novel targets, cyclin B1 and PARP, and indirectly results in the processing of pro-apoptotic BH3-only proteins. CPAF activation induces striking morphological changes in the cell and, later, cell death. Biochemical and ultrastructural analysis of the cell death pathway identify the mechanism of cell death as nonapoptotic. Active CPAF in uninfected human cells thus mimics many features of chlamydial infection, implicating CPAF as a major factor of chlamydial pathogenicity, Chlamydia-associated cell damage, and inflammation