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

Saccade latency toward auditory targets depends on the relative position of the sound source with respect to the eyes

AbstractThe latency of saccadic eye movements evoked by the presentation of auditory and visual targets was studied while starting eye position was either 0 or 20 deg right, or 20 deg left. The results show that for any starting position the latency of visually elicited saccades increases with target eccentricity with respect to the eyes. For auditory elicited saccades and for any starting position the latency decreases with target eccentricity with respect to the eyes. Therefore auditory latency depends on a retinotopic motor error, as in the case of visual target presentation

Speech Analysis by Natural Language Processing Techniques: A Possible Tool for Very Early Detection of Cognitive Decline?

Background: The discovery of early, non-invasive biomarkers for the identification of “preclinical” or “pre-symptomatic” Alzheimer's disease and other dementias is a key issue in the field, especially for research purposes, the design of preventive clinical trials, and drafting population-based health care policies. Complex behaviors are natural candidates for this. In particular, recent studies have suggested that speech alterations might be one of the earliest signs of cognitive decline, frequently noticeable years before other cognitive deficits become apparent. Traditional neuropsychological language tests provide ambiguous results in this context. In contrast, the analysis of spoken language productions by Natural Language Processing (NLP) techniques can pinpoint language modifications in potential patients. This interdisciplinary study aimed at using NLP to identify early linguistic signs of cognitive decline in a population of elderly individuals.Methods: We enrolled 96 participants (age range 50–75): 48 healthy controls (CG) and 48 cognitively impaired participants: 16 participants with single domain amnestic Mild Cognitive Impairment (aMCI), 16 with multiple domain MCI (mdMCI) and 16 with early Dementia (eD). Each subject underwent a brief neuropsychological screening composed by MMSE, MoCA, GPCog, CDT, and verbal fluency (phonemic and semantic). The spontaneous speech during three tasks (describing a complex picture, a typical working day and recalling a last remembered dream) was then recorded, transcribed and annotated at various linguistic levels. A multidimensional parameter computation was performed by a quantitative analysis of spoken texts, computing rhythmic, acoustic, lexical, morpho-syntactic, and syntactic features.Results: Neuropsychological tests showed significant differences between controls and mdMCI, and between controls and eD participants; GPCog, MoCA, PF, and SF also discriminated between controls and aMCI. In the linguistic experiments, a number of features regarding lexical, acoustic and syntactic aspects were significant in differentiating between mdMCI, eD, and CG (non-parametric statistical analysis). Some features, mainly in the acoustic domain also discriminated between CG and aMCI.Conclusions: Linguistic features of spontaneous speech transcribed and analyzed by NLP techniques show significant differences between controls and pathological states (not only eD but also MCI) and seems to be a promising approach for the identification of preclinical stages of dementia. Long duration follow-up studies are needed to confirm this assumption

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

Contexto socio-ambiental en áreas urbanas : aproximaciones a partir de un caso de estudio de Córdoba

Introducción: Conocer el ambiente social, físico y alimentario, es fundamental para analizar el proceso de determinación socio-ambiental de la salud. Sin embargo, son escasos los estudios que aborden el estudio de estas dimensiones de manera integral en Córdoba, Argentina. Objetivos: 1) Identificar las principales características socio-contextuales de los barrios de la ciudad de Córdoba en el año 2010. 2) Describir la situación socio- ambiental en el área de influencia del Centro de Salud (CS) N°22, en la ciudad de Córdoba en el año 2018, en base a las dimensiones: ambiente físico, ambiente social y ambiente alimentario. Metodología: Estudio ecológico mixto. Primera etapa: estudio ecológico de grupos múltiples, unidad de observación: todos los barrios de la ciudad de Córdoba. Segunda etapa: estudio de caso, unidad de observación: recorte territorial, área de influencia del CS N°22. Para el ambiente social, se utilizaron indicadores sociodemográficos del censo (2010), y se realizó un Análisis Factorial de Componentes Principales (AFCP). Para el ambiente físico, se realizó una observación directa, empleando la Evaluación Ambiental Rápida (EAR). El ambiente alimentario fue valorado a partir de observación directa y mediante la herramienta Street View de Google. Resultados: Ambiente social: fueron identificados cuatro escenarios en la ciudad de Córdoba. Los barrios del área de influencia del CS N°22 adhieren más a los escenarios caracterizados por mejores condiciones de vida materiales y educativas. Ambiente físico: los resultados de la EAR fueron positivos, denotaron baja probabilidad de que los factores ambientales afecten la salud de la población. Ambiente alimentario: los puntos de venta de alimentos más frecuentes fueron los almacenes y kioscos, y los menos frecuentes supermercados, dietéticas y distribuidoras. Conclusiones: Fueron identificados diversos escenarios sociales en la ciudad de Córdoba. El área de influencia del CS N°22 presentó un ambiente social y físico relativamente favorable. En cuanto al ambiente alimentario, predominan los puntos de venta de alimentos considerados como no saludables. El abordaje simultáneo de diversas dimensiones contextuales constituye un aspecto innovador, que puede impulsar a la realización de futuras investigaciones en el área de la epidemiología social y nutricional.Fil: Ardissono, Carla Andrea. Universidad Católica de Córdoba. Facultad de Ciencias de Salud; ArgentinaFil: Beltrami, María Daniela. Universidad Católica de Córdoba. Facultad de Ciencias de Salud; Argentin

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

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

Investigation of adhesion and mechanical properties of human glioma cells by single cell force spectroscopy and atomic force microscopy.

Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma--HG--and Gasc for low-grade glioma--LG) that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics

Dissecting the heterogeneity of circulating tumor cells in metastatic breast cancer: Going far beyond the needle in the Haystack

6noAlthough the enumeration of circulating tumor cells (CTC) defined as expressing both epithelial cell adhesion molecule and cytokeratins (EpCAM+/CK+) can predict prognosis and response to therapy in metastatic breast, colon and prostate cancer, its clinical utility (i.e., the ability to improve patient outcome by guiding therapy) has not yet been proven in clinical trials. Therefore, scientists are now focusing on the molecular characterization of CTC as a way to explore its possible use as a “surrogate” of tumor tissues to non-invasively assess the genomic landscape of the cancer and its evolution during treatment. Additionally, evidences confirm the existence of CTC in epithelial-to-mesenchymal transition (EMT) characterized by a variable loss of epithelial markers. Since the EMT process can originate cells with enhanced invasiveness, stemness and drug-resistance, the enumeration and characterization of this population, perhaps the one truly responsible of tumor recurrence and progression, could be more clinically useful. For these reasons, several devices able to capture CTC independently from the expression of epithelial markers have been developed. In this review, we will describe the types of heterogeneity so far identified and the key role played by the epithelial-to-mesenchymal transition in driving CTC heterogeneity. The clinical relevance of detecting CTC-heterogeneity will be discussed as well.openopenBulfoni, Michela; Turetta, Matteo; Del Ben, Fabio; Di Loreto, Carla; Beltrami, Antonio Paolo; Cesselli, DanielaBulfoni, Michela; Turetta, Matteo; Del Ben, Fabio; DI LORETO, Carla; Beltrami, Antonio Paolo; Cesselli, Daniel