Human Multipotent Mesenchymal Stromal Cells from Distinct Sources Show Different In Vivo Potential to Differentiate into Muscle Cells When Injected in Dystrophic Mice

Limb-girdle muscular dystrophies are a heterogeneous group of disorders characterized by progressive degeneration of skeletal muscle caused by the absence or deficiency of muscle proteins. The murine model of Limb-Girdle Muscular Dystrophy 2B, the SJL mice, carries a deletion in the dysferlin gene. Functionally, this mouse model shows discrete muscle weakness, starting at the age of 4-6 weeks. The possibility to restore the expression of the defective protein and improve muscular performance by cell therapy is a promising approach for the future treatment of progressive muscular dystrophies (PMD). We and others have recently shown that human adipose multipotent mesenchymal stromal cells (hASCs) can differentiate into skeletal muscle when in contact with dystrophic muscle cells in vitro and in vivo. Umbilical cord tissue and adipose tissue are known rich sources of multipotent mesenchymal stromal cells (MSCs), widely used for cell-based therapy studies. The main objective of the present study is to evaluate if MSCs from these two different sources have the same potential to reach and differentiate in muscle cells in vivo or if this capability is influenced by the niche from where they were obtained. In order to address this question we injected human derived umbilical cord tissue MSCs (hUCT MSCs) into the caudal vein of SJL mice with the same protocol previously used for hASCs; we evaluated the ability of these cells to engraft into recipient dystrophic muscle after systemic delivery, to express human muscle proteins in the dystrophic host and their effect in functional performance. These results are of great interest for future therapeutic application.

Acquisition of Pavlovian Fear Conditioning Using beta-Adrenoceptor Activation of the Dorsal Premammillary Nucleus as an Unconditioned Stimulus to Mimic Live Predator-Threat Exposure

In the present work, we sought to mimic the internal state changes in response to a predator threat by pharmacologically stimulating the brain circuit involved in mediating predator fear responses, and explored whether this stimulation would be a valuable unconditioned stimulus (US) in an olfactory fear conditioning paradigm (OFC). The dorsal premammillary nucleus (PMd) is a key brain structure in the neural processing of anti-predatory defensive behavior and has also been shown to mediate the acquisition and expression of anti-predatory contextual conditioning fear responses. Rats were conditioned by pairing the US, which was an intra-PMd microinjection of isoproterenol (ISO; beta-adrenoceptor agonist), with amyl acetate odor-the conditioned stimulus (CS). ISO (10 and 40 nmol) induced the acquisition of the OFC and the second-order association by activation of beta-1 receptors in the PMd. Furthermore, similar to what had been found for contextual conditioning to a predator threat, atenolol (beta-1 receptor antagonist) in the PMd also impaired the acquisition and expression of OFC promoted by ISO. Considering the strong glutamatergic projections from the PMd to the dorsal periaqueductal gray (dPAG), we tested how the glutamatergic blockade of the dPAG would interfere with the OFC induced by ISO. Accordingly, microinjections of NMDA receptor antagonist (AP5, 6 nmol) into the dPAG were able to block both the acquisition, and partially, the expression of the OFC. In conclusion, we have found that PMd beta-1 adrenergic stimulation is a good model to mimic predatory threat-induced internal state changes, and works as a US able to mobilize the same systems involved in the acquisition and expression of predator-related contextual conditioning. Neuropsychopharmacology (2011) 36, 926-939; doi:10.1038/npp.2010.231; published online 5 January 2011

A study of the catecholaminergic inputs to the dorsal premammillary nucleus

The dorsal premammillary nucleus (PMd) is one of the most responsive hypothalamic sites during exposure to a predator or its odor, and to a context previously associated with a predatory threat; and lesions or pharmacological inactivation centered therein severely reduced the anti-predatory defensive responses. Previous studies have shown that beta adrenergic transmission in the PMd seems critical to the expression of fear responses to predatory threats. In the present study, we have investigated the putative sources of catecholaminergic inputs to the PMd. To this end, we have first described the general pattern of catecholaminergic innervation of the PMd by examining the distribution and morphology of the tyrosine hydroxylase (TH) immunoreactive fibers in the nucleus; and next, combining Fluoro Gold (FG) tracing experiments and TH immunostaining, we determined the putative sources of catecholaminergic inputs to the nucleus. Our results revealed that the PMd presents a moderately dense plexus of catecholaminergic fibers that seems to encompass the rostral pole and ventral border of the nucleus. Combining the results of the FG tract-tracing and TH immunostaining, we observed that the locus coeruleus was the sole brain site that contained double FG and TH immunostained cells. In summary, the evidence suggests that the locus coeruleus is seemingly a part of the circuit responding to predatory threats, and, as shown by the present results, is the sole source of catecholaminergic inputs to the PMd, providing noradrenergic inputs to the nucleus, which, by acting via beta adrenoceptor, seems to be critical for the expression of anti-predatory responses. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

New Perspectives on beta-Adrenergic Mediation of Innate and Learned Fear Responses to Predator Odor

In the present study, we investigated the role of noradrenergic transmission in unconditioned and conditioned responses to predatory threats. First, we examined the effects of systemically injected beta-blockers on unconditioned and contextual conditioned response to cat odor. The centrally acting beta-blocker (propranolol) was able to impair unconditioned responses, as well as the acquisition of the contextual fear to cat odor; however, the peripherally acting (nadolol) was not effective. Next, we examined the neural substrate underlying the noradrenergic modulation of the defensive response to cat odor and focused on the dorsal premammillary nucleus (PMd), because it represents the hypothalamic site most responsive to predatory threats and, at the same time, presents a dense plexus of noradrenergic fibers. We were able to see that propranolol significantly reduced PMd-Fos expression in response to cat odor and that beta-adrenoceptor blockade in the PMd, before cat odor exposure, reduced defensive responses to the cat odor and to the cat odor-related environment. We have also shown that beta-adrenoceptor blockade in the PMd, before the exposure to cat odor-related context, impaired the contextual conditioned responses. Overall, the present results provide convincing evidence suggesting that central noradrenergic mediation is critical for the expression of unconditioned and contextual conditioned antipredatory responses. We have further shown that the PMd appears to be an important locus to mediate these beta-adrenoceptor effects.

Sensing danger through the olfactory system: The role of the hypothalamic dorsal premammillary nucleus

The dorsal premammillary nucleus (PMd) has a critical role on the expression of defensive responses to predator odor. Anatomical evidence suggests that the PMd should also modulate memory processing through a projecting branch to the anterior thalamus. By using a pharmacological blockade of the PMd with the NMDA-receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5), we were able to confirm its role in the expression of unconditioned defensive responses, and further revealed that the nucleus is also involved in influencing associative mechanisms linking predatory threats to the related context. We have also tested whether olfactory fear conditioning, using coffee odor as CS, would be useful to model predator odor. Similar to cat odor, shock-paired coffee odor produced robust defensive behavior during exposure to the odor and to the associated context. Shock-paired coffee odor also up-regulated Fos expression in the PMd, and, as with cat odor, we showed that this nucleus is involved in the conditioned defensive responses to the shock-paired coffee odor and the contextual responses to the associated environment. (C) 2008 Elsevier Ltd. All rights reserved.

Hypothalamic sites responding to predator threats - the role of the dorsal premammillary nucleus in unconditioned and conditioned antipredatory defensive behavior

In this study we provide a comprehensive analysis of the hypothalamic activation pattern during exposure to a live predator or an environment previously associated with a predator. Our results support the view that hypothalamic processing of the actual and the contextual predatory threats share the same circuit, in which the dorsal premammillary nucleus (PMd) plays a pivotal role in amplifying this processing. To further understand the role of the PMd in the circuit organizing antipredatory defensive behaviors, we studied rats with cytotoxic PMd lesions during cat exposure and examined the pattern of behavioral responses as well as how PMd lesions affect the neuronal activation of the systems engaged in predator detection, in contextual memory formation and in defensive behavioral responses. Next, we investigated how pharmacological blockade of the PMd interferes with the conditioned behavioral responses to a context previously associated with a predator, and how this blockade affects the activation pattern of periaqueductal gray (PAG) sites likely to organize the conditioned behavioral responses to the predatory context. Behavioral observations indicate that the PMd interferes with both unconditioned and conditioned antipredatory defensive behavior. Moreover, we have shown that the PMd influences the activation of its major projecting targets, i.e. the ventral part of the anteromedial thalamic nucleus which is likely to influence mnemonic processing, and PAG sites involved in the expression of antipredatory unconditioned and conditioned behavioral responses. Of particular relevance, this work provides evidence to elucidate the basic organization of the neural circuits integrating unconditioned and contextual conditioned responses to predatory threats.

Evidence for the thalamic targets of the medial hypothalamic defensive system mediating emotional memory to predatory threats

Previous studies from our laboratory have documented that the medial hypothalamic defensive system is critically involved in processing actual and contextual predatory threats, and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats. Anatomical findings suggest that the PMd is in a position to modulate memory processing through a projecting branch to specific thalamic nuclei, i.e., the nucleus reuniens (RE) and the ventral part of the anteromedial nucleus (AMv). In the present study, we investigated the role of these thalamic targets in both unconditioned (i.e., fear responses to predatory threat) and conditioned (i.e., contextual responses to predator-related cues) defensive behaviors. During cat exposure, all experimental groups exhibited intense defensive responses with the animals spending most of the time in the home cage displaying freezing behavior. However, during exposure to the environment previously associated with a cat, the animals with combined RE + AMv lesions, and to a lesser degree, animals with single AMv unilateral lesions, but not animals with single RE lesions, presented a reduction of contextual conditioned defensive responses. Overall, the present results provide clear evidence suggesting that the PMd`s main thalamic targets (i.e., the nucleus reuniens and the AMv) seem to be critically involved in the emotional memory processing related to predator cues. (C) 2010 Elsevier Inc. All rights reserved.

Prevention of mental disorders: evidence, challenges and opportunities

Modelling studies suggest that less than 30% of the burden of mental disorders can be averted, even with optimal care and access to services. This points to the need to reduce the incidence of mental disorders, utilising evidence-based prevention strategies and policy action. In this cross-journal article collection (http://www.biomedcentral.com/series/PMD), the case for prevention is made by identifying initiatives with established efficacy, as well as opportunities and targets for the prevention of mental disorders in early life, in the workplace and at the population level. These articles provide reviews, systematic and narrative, outlining the evidence base for prevention approaches, as well as comment and debate designed to prompt discussion and a reconsideration of strategies for prevention. Barriers to expanding the research into prevention include the reluctance of governments and funding bodies to invest in research and policy action that may take many years to manifest benefits. The case for the cost-effectiveness of preventing mental disorders needs to be strongly argued and new cross-disciplinary, intersectoral initiatives and policies developed for the prevention of mental disorders across the lifespan.

Qualidade de vida do servidor da Universidade Federal do Rio Grande do Norte em condição crônica de saúde

The study aimed to analyze the influence of chronic health conditions (CHC) on quality of life (QOL) of UFRN servers assaulted by CHC. It is a descriptive and cross-sectional study with prospective data and quantitative approach, accomplished in the ambulatory clinic of the Department of Server Assistance (DSA) of the Pro-Rectory of Human Resources, during three months. The sample was composed by accessibility, totaling 215 people, being 153 active and 62 inactive servers, in chronic health condition. The data were collected through the application of the sociodemographic characterization, health, environmental and laboral form, the Medical Outcome Study 36-Item Short Form (SF-36). The study was evaluated by the HUOL Ethics Committee (CAAE no. 0046.0.294.000.10), obtaining assent. The results were analyzed in the SPSS 15.0 program through the descriptive and inferential statistics. It was identified servants predominantly male (59,1%), under 60 years old, married or in stable union, Catholics, brown color, living in the capital and residents in own home. Regarding labor issues, there was a predominance of active servers technical-administrative with intermediate and medium level positions and small proportion of docents. Among the CHC, the non-communicable diseases - NCDs (95.8%) had a higher frequency, followed by persistent mental disorders - PMDs (18.6%) and, finally, the continuous and structural physical deficiency - CSPD (16.9 %). The QOL of servers was considered good, with a mean score of 72.5 points in the total score, with the most affected domains: physical (59.1), general health (66.2), bodily pain (66.3) and functional aspects (72.0). The mental health dimension (76.5) had a better average than the physical dimension (68.0 points). It was found that the decrease in QOL scores is significant statistically related to higher number of CHC (ρ <0.001), with no statistical significance regarding the functional situation (p = 0.259). The administrative technicians of elementary, primary, secondary levels and docents had the worst QOL scores. After the correlation analysis of CHC with the domains and dimensions of the SF-36, there was statistically significant, negative and weak correlation of the domains: functional aspect (ρ = 0.002, r = -0.207), physical aspects (ρ = 0.007; r = -0.183), vitality (ρ = 0.002, r = -0.213), social function (ρ = 0.000, r = -0.313), emotional aspects (ρ = 0.000, r = -0.293), mental health (ρ = 0.000 , r = -0.238), physical health dimension (ρ = 0.002, r = -0.210) and mental health dimension (ρ = 0.000, r = -0.298). The presence of PMD isolated or together, contributed to a lower SF-36 scores, being the domains variation of mean significant, except for bodily pain, general health and physical aspects. By correlating the categories of CHC and QOL, there was a weak correlation (r ≤ -0.376) and significant (ρ ≤ 0.011), mainly related to the NCD, PMDs and NCD + PMD, affecting the mental health, social function, emotional aspects, vitality and functional aspect domains. Front of the results, it was concludes that the servers quality of life is influenced by the CHC. Thus, it was inferred that the presence of CHC causes a negative effect on quality of life, leading the active and inactive servers to exposure their overall life activities and work over the years, due to the morbidity affected, mainly related to NCDs and PMDs. Descriptors: Quality of life. Chronic disease. Occupational Health. Nursing

Processo markoviano de decisão para alocação dinâmica de recursos e controle de admissão de conexão em redes IEEE 802.16

Este trabalho apresenta uma solução para o problema de controle admissão de conexão e alocação dinâmica de recursos em redes IEEE 802.16 através da modelagem de um Processo Markoviano de Decisão (PMD) utilizando o conceito de degradação de largura de banda, o qual é baseado nos requisitos diferenciados de largura de banda das classes de serviço do IEEE 802.16. Para o critério de desempenho do PMD é feita a atribuição de diferentes retornos a cada classe de serviço, fazendo assim o tratamento diferenciado de cada fluxo. Nesse sentido, é possível avaliar a política ótima, obtida através de um algoritmo de iteração de valores, considerando aspectos como o nível de degradação médio das classes de serviço, utilização dos recursos e probabilidades de bloqueios de cada classe de serviço em relação à carga do sistema. Resultados obtidos mostram que o método de controle markoviano proposto é capaz de priorizar as classes de serviço consideradas mais relevantes para o sistema.

Narrativas Multimodais: a imagem dos matemáticos em performances matemáticas digitais

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of maturity levels in the management of product development: case studies in the capital goods industry

In recent approaches to the management of product development process (PDP), maturity levels have attracted the attention of practitioners and researchers. The CMMI model contributes to evaluate the maturity levels and improvement of the product development process management. This paper, based on CMMI model, analyzes the practices adopted in two companies of the capital goods industry, which develop and manufacture equipment upon request. It was observed that on account of market conditioning factors and different practices adapted to PDP management, these companies are at different maturity levels. One company is at the initial level of maturity while the other at the most advanced one. It was also noted that the application of CMMI model can provide improvement to PDP management, as well as present guidelines to achieve higher maturity levels, adequate to companies' needs.

Open innovation and user s involvement in new product development: a case study in the automotive sector

Innovation is an essential factor for obtaining competitive advantages. The search for external knowledge sources for product creation, which can contribute to the innovation process, has become a constant among companies, and users play an important role in this search. In this study, we aimed to analyze user’s involvement in the product development process based on open innovation concepts. We used the unique case study research method. This study was carried out in an automotive company that has developed a project of a concept car involving user’s through the Web 2.0. With such scope, the research demonstrates that users can contribute not only with generation of ideas but also with the innovation process itself.

New product development in brazilian technology-based small and medium enterprises

This article examines new product development (NPD) in small and medium-sized Brazilian enterprises (SMEs) in two technology-based industries: medical devices and process control automation devices. A conceptual model that categorizes factors that contribute to the success of a new product was established. The data were collected from a sample of 62 Brazilian SMEs. The conceptual model was tested to examine the relationships between NPD practices and new product success. Data analysis reveals that new product success in medical device companies is related to organizational characteristics such as NPD proficiency and marketing skills; while in process control automation device companies, they deal in a large degree with product differentiation, innovation and capability to analyze the targeted market. Due to the relatively small sample size, caution should be exercised when interpreting the results.

Simultaneous optical signal-to-noise ratio and differential group delay monitoring based on degree of polarization measurements in optical communications systems

We present a simultaneous optical signal-to-noise ratio (OSNR) and differential group delay (DGD) monitoring method based on degree of polarization (DOP) measurements in optical communications systems. For the first time in the literature (to our best knowledge), the proposed scheme is demonstrated to be able to independently and simultaneously extract OSNR and DGD values from the DOP measurements. This is possible because the OSNR is related to maximum DOP, while DGD is related to the ratio between the maximum and minimum values of DOP. We experimentally measured OSNR and DGD in the ranges from 10 to 30 dB and 0 to 90 ps for a 10 Gb/s non-return-to-zero signal. A theoretical analysis of DOP accuracy needed to measure low values of DGD and high OSNRs is carried out, showing that current polarimeter technology is capable of yielding an OSNR measurement within 1 dB accuracy, for OSNR values up to 34 dB, while DGD error is limited to 1.5% for DGD values above 10 ps. For the first time to our knowledge, the technique was demonstrated to accurately measure first-order polarization mode dispersion (PMD) in the presence of a high value of second-order PMD (as high as 2071 ps(2)). (C) 2012 Optical Society of America