stem cell senescence in diabetes forgetting the sweet old memories

Diabetes 2014;63:1841–1843 | DOI: 10.2337/db14-0275 Diabetic cardiomyopathy is identified by a left ventricular dysfunction due to metabolic and cellular abnormalities in the absence of atherosclerosis or hypertension and is one of the leading causes of morbidity and mortality in the diabetic population (1). It is characterized by myocardial necrosis and fibrosis, endothelial dysfunction, and stem cell senescence (2). This latter phenomenon is now considered to be a central mechanism of aging and agerelated pathologies as it has been associated with the reduced ability of tissues to replace lost cells and to repair damage (3,4). In this issue, Vecellio et al. (5) analyzed the intriguing issue of whether stem cells isolated from diabetic hearts have a metabolic memory reminiscen

Guided studies for trumpet ensembles : technique and interpretive fundamentals

Anexos: 1 CD-ROM - repertorio brasileiro para grupos de trompete, 1 DVD - gravação ao vivo da Oficina Trompetando no 1º Festival Internacional de Musica da Unicamp(2005)Orientador: Eduardo Augusto OstergrenDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de ArtesResumo: O presente trabalho tem como objetivo principal uma proposta de estudos clínicos e interpretativos visando à prática da música de câmara para trompetes. Foram descritos fundamentos teóricos e procedimentos práticos, apresentados também como estudos e divididos em três estágios: básico, médio e avançado, utilizados nos ensaios laboratoriais da Oficina Trompetando (Unicamp). No estágio avançado, estes estudos foram aplicados a obras musicais, utilizando-se os conceitos de homogeneidade e uniformidade. Como resultado, a aplicação desses conceitos permitiu aos integrantes da Oficina subsídios para uma reflexão teórica aprofundada, um maior domínio técnico do conjunto, e uma melhor compreensão da obra, levando a uma interpretação estilística coerente.Abstract: This study has as its main objective the proposal of clinical and interpretive studies aiming at the practice of chamber music for trumpet ensembles. Theoretical as well as practical procedures have also been presented as studies and divided into three levels: basic, medium and advanced already utilized in laboratory rehearsals of Oficina Trompetando (Unicamp). At the advance stage these studies have been applied to musical works utilizing concepts such as homogeneity and uniformity. As result, the application of these concepts have offered members of Oficina subsidies for a deeper theoretical reflection, a more developed ensemble technique and a better understanding of the work, leading to a coherent stylistic interpretation.MestradoMestre em Músic

A human neuronal model of Niemann Pick C disease developed from stem cells isolated from patient's skin.

Niemann Pick C (NPC) disease is a neurovisceral lysosomal storage disorder due to mutations in NPC1 or NPC2 genes, characterized by the accumulation of endocytosed unesterified cholesterol, gangliosides and other lipids within the lysosomes/late endosomes. Even if the neurodegeneration is the main feature of the disease, the analysis of the molecular pathways linking the lipid accumulation and cellular damage in the brain has been challenging due to the limited availability of human neuronal models.The aim of this study was to develop a human neuronal model of NPC disease by inducing neuronal differentiation of multipotent adult stem cells (MASC) isolated from NPC patients.Stem cells were isolated from 3 NPC patients and 3 controls both from skin biopsies and previously established skin fibroblast cultures. Cells were induced to differentiate along a neuronal fate adapting methods previously described by Beltrami et al, 2007. The surface immunophenotype of stem cells was analyzed by FACS. Stem cell and neuronal markers expression were evaluated by immunofluorescence. Intracellular accumulation of cholesterol and gangliosides were assessed by filipin staining and immunofluorescence, respectively. A morphometric analysis was performed using a Neurite outgrowth image program.After 3 passages in selective medium, MASC isolated either from skin biopsies or previously established skin fibroblast cultures displayed an antigenic pattern characteristic of mesenchymal stem cells and expressed the stem cell markers Oct-4, Nanog, Sox-2 and nestin. A massive lysosomal accumulation of cholesterol was observed only in cells isolated from NPC patients. After the induction of neural differentiation, remarkable morphologic changes were observed and cells became positive to markers of the neuronal lineage NeuN and MAP2. Differentiated cells from NPC patients displayed characteristic features of NPC disease, they showed intracellular accumulation of unesterified cholesterol and GM2 ganglioside and presented morphological differences with respect to cells derived from healthy donors.In conclusion, we generated a human neuronal model of NPC disease through the induction of differentiation of stem cells obtained from patient's easily accessible sources. The strategy described here may be applied to easily generate human neuronal models of other neurodegenerative diseases

Pericytes and cardiac stem cells: common features and peculiarities:Common features and peculiarities

Clinical data and basic research indicate that the structural and functional alterations that characterize the evolution of cardiac disease towards heart failure may be, at least in part, reversed. This paradigm shift is due to the accumulation of evidence indicating that, in peculiar settings, cardiomyocytes may be replenished. Moving from the consideration that cardiomyocytes are rapidly withdrawn from the cell cycle after birth, independent laboratories have tested the hypothesis that cardiac resident stem/progenitor cells resided in mammalian hearts and were important for myocardial repair. After almost two decades of intensive investigation, several (but partially overlapping) cardiac resident stem/progenitor cell populations have been identified. These primitive cells are characterized by mesenchymal features, unique properties that distinguish them from mesodermal progenitors residing in other tissues, and heterogeneous embryological origins (that include the neural crest and the epicardium). A further layer of complexity is related to the nature, in vivo localization and properties of mesodermal progenitors residing in adult tissues. Intriguingly, these latter, whose possible perivascular pericyte/mural cell origin has been shown, have been identified in human hearts too. However, their exact anatomical localization, pathophysiological role, and their relationship with cardiac stem/progenitor cells are emerging only recently. Therefore, aim of this review is to discuss the different origin, the distinct nature, and the complementary effect of cardiac stem cells and pericytes supporting regenerative strategies based on the combined use of both myogenic and angiogenic factors

What was the survival of megaprostheses in lower limb reconstructions after tumor resections?

Analisi retrospettiva delle ricostruzioni dell'arto inferiore con protesi modulariBackground: Prosthetic replacement is the most commonly used option for reconstruction of osteoarticular bone loss resulting from bone neoplasm resection or prosthetic failure. Starting in late 2001, we began exclusively using a single system for large-segment osteoarticular reconstruction after tumor resection; to our knowledge, there are no published series from one center evaluating the use of this implant. Questions/purposes: We investigated the following issues: (1) What is the overall survival, excluding local tumor recurrence, for these endoprostheses used for tumor reconstructions of the lower extremities (knee and hip)? (2) What types of failure were observed in these reconstructions? (3) Do the survival and complications vary according to site of implant? Methods: Between September 2001 and March 2012, we exclusively used this implant for tumor reconstructions. During that time, 278 patients underwent tumor reconstructions of the hip or knee, of whom 200 (72%) were available at a minimum 2 years followup. Seventy-eight patients were excluded from the study for insufficient followup as a result of early death (42) or loss at followup (36). The reconstruction types were the following: proximal femur (69 cases), distal femur (87), proximal tibia (32), and total knee (12). Failures were classified according to the Henderson classification. Nine patients among those with followup shorter than 2 years had presented one or more failures and they were included in our analysis but separately evaluated. Results: Overall survival (no further surgical procedures of any type after primary surgery), excluding Type 5 failure (tumor recurrence), was 75.9% at 5 years and 66.2% at 10 years. Seventy-one failures occurred in 58 implants (29%). Mechanical failures accounted for 59.2% and nonmechanical failures for 40.8%. The first causes of failure of the implants were the result of soft tissue failure in 6%, aseptic loosening in 3%, structural failure in 7%, infection in 8.5%, and tumor recurrence in 4.5% of the whole series. Nine implants sustained two or more failures. Overall incidence of infection was 9.5%. No statistically significant differences were observed according to anatomical site. Conclusions: Like in the case with many such complex oncologic reconstructions, the failure rate at short- to midterm in this group was over 20%. Comparative trials are called for to ascertain whether one implant is superior to another. Infection and structural failure were the most frequent modes of failure in our experience. Level of Evidence: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence

The lizard celestial compass detects linearly polarized light in the blue

SummaryThe present study first examined whether ruin lizards Podarcis sicula are able to orientate using plane polarized light produced by a LCD screen. Ruin lizards were trained and tested indoors, inside an hexagonal Morris water maze, positioned under the LCD screen producing white polarized light with a single E-vector, which provided an axial cue. White polarized light did not include wavelengths in the UV. Lizards orientated correctly either when tested with E-vector parallel to the training axis or after 90° rotation of the E-vector direction, and thus validating the apparatus. Further experiments examined whether in ruin lizards there is a preferential region of the light spectrum to perceive the E-vector direction of polarized light. For this purpose, lizards reaching learning criteria under white polarized light were subdivided into 4 experimental groups. Each group was respectively tested for orientation under a different spectrum of plane polarized light (named red, green, cyan and blue) with equalized photon flux density. Lizards tested under blue polarized light orientated correctly, whereas lizards tested under red polarized light were completely disoriented. Green polarized light was barely discernible by lizards, and thus insufficient for a correct functioning of their compass. When exposed to cyan polarized light, lizard orientation performances were optimal, indistinguishable from lizards detecting blue polarized light. Overall, the present results demonstrate that perception of linear polarization in the blue is necessary - and sufficient - for a proper functioning of the sky polarization compass of ruin lizards. This may be adaptively important, since detection of polarized light in the blue improves functioning of the polarization compass under cloudy skies, i.e. when the alternative celestial compass based on detection of the sun disk is rendered useless because the sun is obscured by clouds

Cardiac Cell Senescence and Redox Signaling

Aging is characterized by a progressive loss of the ability of the organism to cope with stressors and to repair tissue damage. As a result, chronic diseases, including cardiovascular disease, increase their prevalence with aging, underlining the existence of common mechanisms that lead to frailty and age-related diseases. In this frame, the progressive decline of the homeostatic and reparative function of primitive cells has been hypothesized to play a major role in the evolution of cardiac pathology to heart failure. Although initially it was believed that reactive oxygen species (ROS) were produced in an unregulated manner as a byproduct of cellular metabolism, causing macromolecular damage and aging, accumulating evidence indicate the major role played by redox signaling in physiology. Aim of this review is to critically revise evidence linking ROS to cell senescence and aging and to provide evidence of the primary role played by redox signaling, with a particular emphasis on the multifunctional protein APE1/Ref in stem cell biology. Finally, we will discuss evidence supporting the role of redox signaling in cardiovascular cells

Adult cardiac stem cell aging: A reversible stochastic phenomenon?

Aging is by far the dominant risk factor for the development of cardiovascular diseases, whose prevalence dramatically increases with increasing age reaching epidemic proportions. In the elderly, pathologic cellular and molecular changes in cardiac tissue homeostasis and response to injury result in progressive deteriorations in the structure and function of the heart. Although the phenotypes of cardiac aging have been the subject of intense study, the recent discovery that cardiac homeostasis during mammalian lifespan is maintained and regulated by regenerative events associated with endogenous cardiac stem cell (CSC) activation has produced a crucial reconsideration of the biology of the adult and aged mammalian myocardium. The classical notion of the adult heart as a static organ, in terms of cell turnover and renewal, has now been replaced by a dynamic model in which cardiac cells continuously die and are then replaced by CSC progeny differentiation. However, CSCs are not immortal. They undergo cellular senescence characterized by increased ROS production and oxidative stress and loss of telomere/telomerase integrity in response to a variety of physiological and pathological demands with aging. Nevertheless, the old myocardium preserves an endogenous functionally competent CSC cohort which appears to be resistant to the senescent phenotype occurring with aging. The latter envisions the phenomenon of CSC ageing as a result of a stochastic and therefore reversible cell autonomous process. However, CSC aging could be a programmed cell cycle-dependent process, which affects all or most of the endogenous CSC population. The latter would infer that the loss of CSC regenerative capacity with aging is an inevitable phenomenon that cannot be rescued by stimulating their growth, which would only speed their progressive exhaustion. The resolution of these two biological views will be crucial to design and develop effective CSC-based interventions to counteract cardiac aging not only improving health span of the elderly but also extending lifespan by delaying cardiovascular disease-related deaths

Role of microenvironment in glioma invasion: What we learned from in vitro models

The invasion properties of glioblastoma hamper a radical surgery and are responsible for its recurrence. Understanding the invasion mechanisms is thus critical to devise new therapeutic strategies. Therefore, the creation of in vitro models that enable these mechanisms to be studied represents a crucial step. Since in vitro models represent an over-simplification of the in vivo system, in these years it has been attempted to increase the level of complexity of in vitro assays to create models that could better mimic the behaviour of the cells in vivo. These levels of complexity involved: 1. The dimension of the system, moving from two-dimensional to three-dimensional models; 2. The use of microfluidic systems; 3. The use of mixed cultures of tumour cells and cells of the tumour micro-environment in order to mimic the complex cross-talk between tumour cells and their micro-environment; 4. And the source of cells used in an attempt to move from commercial lines to patient-based models. In this review, we will summarize the evidence obtained exploring these different levels of complexity and highlighting advantages and limitations of each system used