The Assault on Human Rigths and the Resilience of the Andean Dream: Health Inequities in Ecuador. IV Annual Distinguished Lecture sponsored by the Center for Research on Ethnicity, Culture and Health; School of Public Health; University of Michigan

The point of departure for these reflections is life, since its protection is the central purpose encouraging the defense of human rights and of public health. Life in the Andes has an exceptional diversity. Particularly in Ecuador, my country, this diversity constitutes a characteristic sign that is expressed in two main forms: natural megadiversity and multiculturalism. Indeed, Ecuador’s small territory synthesizes practically all types of lifezones that exist on Earth, having received the gift of high average rates of solar energy and abundant nutritional sources, which have facilitated the natural reproduction of countless species that show their beautiful vitality in the variety of ecosystems that compose the Andean mountain range, the tropical plains, the Amazon humid forests, and the Galapagos Islands. But besides being a highly biodiverse country, it is also a plurinational and multi-cultural society, in which the activity of human beings, organized into social conglomerates of different historical and cultural backgrounds, have formed more than a dozen nations and peoples. Regrettably this natural and human wealth has not been able to bear its best fruits due to the violent operation of a deep social inequity – unfortunately also one of the highest in the Americas—which conspires against life and is reproduced in national and international inequitable relations. This structural inequity has changed its form throughout the centuries and currently has reached its highest and most perverse level of development.

Sustainable development of human settlements: achievements and challenges in housing and urban policy in Latin America and the Caribbean

Includes bibliography

Environmental development in Brazilian companies: The role of human resource management

Specialized literature states that proper environmental management at companies requires support from human resource management. This occurs because the more efficient and effective human resource management is, the more it tends to contribute towards the organization's objectives. Considering that environmental management is an emerging organizational objective, human resource practices, when efficient and effective, tend to incorporate environmental goal and to become greener. In order to contribute to this emerging field of research, this paper reports on an empirical study about the relationship between human resources and environmental management at 75 Brazilian companies. The data collected were analyzed statistically using Structural Equation Modeling. The main results indicated that human resource management practices tend to statistically significant relate to environmental management at analyzed companies, through validation of H 1, but his relationship can be considered weak. © 2012 Elsevier B.V.

“A gente tem uma vida lá fora...”: relações entre gestão de recursos humanos e sociabilidade das pessoas empregadas nos supermercados da Região Metropolitana de Belém

A gestão de recursos humanos (RH) representa teoricamente uma abordagem da gestão empresarial voltada à organização do trabalho visando seu melhor aproveitamento e, em particular, o envolvimento dos trabalhadores nos objetivos da empresa. As práticas de gestão incidem não somente sobre o trabalho em si, mas também de maneira complexa nas interações sociais ocorridas no ambiente de trabalho, bem como na vida pessoal dos trabalhadores, de acordo com as premissas e práticas do estilo de gestão predominante. O presente estudo procura conhecer a natureza das correlações entre gestão de recursos humanos e sociabilidade dos trabalhadores, isto é, sua capacidade de tecer e de manter laços sociais diversos, a partir dos pontos de vista dos trabalhadores. Tomaram-se como referência empírica quatro redes de supermercados na Região Metropolitana de Belém, Pará. O setor é grande empregador, vem se modernizando expressivamente nas duas últimas décadas, implementando alguns procedimentos de gestão de RH e se mantém ao abrigo da forte concorrência de grupos nacionais e internacionais que se observa em outras capitais do país. A metodologia incluiu observações sistemáticas, análise documental e entrevistas estruturadas e semi-estruturadas em profundidade, respectivamente com trezentos e oitenta e quatorze trabalhadores, estes últimos selecionados dentre os constantes da amostra maior. As entrevistas versaram sobre atributos sociais e demográficos, trajetória ocupacional e padrões de relacionamento pessoal e profissional. Abrangeram, também, as percepções sobre regras e atitudes no trabalho, com base nas normas constantes dos manuais de serviço das empresas. Incluem-se trinta e quatro itens em uma escala de Lickert. Esses itens foram dispostos em fatores, sendo dois sobre gestão – qualidade do trabalho (QT) e introjeção das normas organizacionais (IN) – e três sobre sociabilidade – confiança (CF), manutenção (MR) e utilidade das relações (UT) no trabalho. Os entrevistados respondiam aos itens, ajustando o grau de sua percepção sobre cada um deles. Tais dados foram submetidos à técnica estatística exploratória Análise de Correspondência (AC) de maneira a verificar a correlação entre os fatores da escala e as características dos entrevistados. Sobre as correlações entre gestão e sociabilidade, sobressaiu em primeiro lugar o regime de trabalho. Jornadas extensas, escalas variáveis, longos intervalos diários e a política de qualificação em serviço (on the job) absorvem quase integralmente o tempo do empregado e dificultam manter relações pessoais ou mesmo estender aquelas formadas no ambiente de trabalho para além deste espaço. Dificulta também investir nos estudos, outra esfera de sociabilidade, o que surpreende em uma amostra cuja faixa etária predominante não ultrapassava trinta anos e cuja ocupação tem poucas possibilidades de carreira. Nesse quadro geral de restrições, a condição de gênero e de família também foi relevante, pois as mulheres, em particular as mães, indicaram menos atividades de lazer, em grupos menores e com mínima presença de colegas de trabalho, em comparação aos homens. Por outro lado, encontraram-se alguns casos de pessoas que construíram relações de conteúdo afetivo no ambiente de trabalho, mesmo a convivência se restringindo à empresa. Outra característica marcante foi a dependência do apoio familiar para o exercício da atividade laboral e para o enfrentamento das vicissitudes do mercado de trabalho. A importância dos laços familiares foi reforçada pelo longo tempo de moradia no mesmo bairro e, em proporção significativa, na mesma residência, em muitos casos a moradia era próxima ou no mesmo domicílio dos pais ou sogros, o que facilitava a ajuda mútua. Outro aspecto que se destacou da gestão de RH foi a imprecisão percebida nos critérios de ascensão profissional e de aplicação das normas, contribuindo para a existência de conflitos velados. Ao estabelecer laços sociais, os empregados depositam uma confiança seletiva, expressa no pequeno número de pessoas em quem se confiava no trabalho. Vale notar aqui também uma pequena variação entre homens e mulheres, pois eles confiavam mais que elas nos colegas. A AC mostrou sensíveis diferenças de percepção sobre qualidade do trabalho e introjeção de normas entre os trabalhadores com primeiro registro em carteira e aqueles com experiência anterior de trabalho formal. Os primeiros notaram um controle (vigilância) mais incisivo da gestão e expressaram menor anuência às regras organizacionais, enquanto que os demais não percebiam o controle da mesma forma e se viam como cumpridores dessas regras. Esses resultados foram interpretados como decorrentes das diferentes trajetórias anteriores, em ocupações formais ou informais, ou por se tratar do primeiro emprego. Não se pode afirmar que as restrições à sociabilidade se devam exclusivamente às características da gestão nesse setor, tendo em vista a incidência de outros fatores, tais como a condição sócio-econômica da família ou o tempo do vinculo empregatício, em média de dois anos entre os entrevistados, que podem ter contribuído para esses resultados.

Stream sediments analysis for geochemical mapping of Romagna Apennines (Northern Italy): monitoring and management tool of environmental resources at various scales

Geochemical mapping is a valuable tool for the control of territory that can be used not only in the identification of mineral resources and geological, agricultural and forestry studies but also in the monitoring of natural resources by giving solutions to environmental and economic problems. Stream sediments are widely used in the sampling campaigns carried out by the world's governments and research groups for their characteristics of broad representativeness of rocks and soils, for ease of sampling and for the possibility to conduct very detailed sampling In this context, the environmental role of stream sediments provides a good basis for the implementation of environmental management measures, in fact the composition of river sediments is an important factor in understanding the complex dynamics that develop within catchment basins therefore they represent a critical environmental compartment: they can persistently incorporate pollutants after a process of contamination and release into the biosphere if the environmental conditions change. It is essential to determine whether the concentrations of certain elements, in particular heavy metals, can be the result of natural erosion of rocks containing high concentrations of specific elements or are generated as residues of human activities related to a certain study area. This PhD thesis aims to extract from an extensive database on stream sediments of the Romagna rivers the widest spectrum of informations. The study involved low and high order stream in the mountain and hilly area, but also the sediments of the floodplain area, where intensive agriculture is active. The geochemical signals recorded by the stream sediments will be interpreted in order to reconstruct the natural variability related to bedrock and soil contribution, the effects of the river dynamics, the anomalous sites, and with the calculation of background values be able to evaluate their level of degradation and predict the environmental risk.

Fetuin-A and cystatin C are endogenous inhibitors of human meprin metalloproteases

Meprin and , zinc metalloproteinases, play significant roles in inflammation, including inflammatory bowel disease (IBD), possibly by activating cytokines, like interleukin 1 , interleukin 18, or tumor growth factor . Although a number of potential activators for meprins are known, no endogenous inhibitors have been identified. In this work, we analyzed the inhibitory potential of human plasma and identified bovine fetuin-A as an endogenous meprin inhibitor with a K(i) (inhibition constant) of 4.2 × 10(-5) M for meprin and a K(i) of 1.1 × 10(-6) M meprin . This correlated with data obtained for a fetuin-A homologue from carp (nephrosin inhibitor) that revealed a potent meprin and inhibition (residual activities of 27 and 22%, respectively) at a carp fetuin concentration of 1.5 × 10(-6) M. Human fetuin-A is a negative acute phase protein involved in inflammatory diseases, thus being a potential physiological regulator of meprin activity. We report kinetic studies of fetuin-A with the proteolytic enzymes astacin, LAST, LAST_MAM, trypsin, and chymotrypsin, indeed demonstrating that fetuin-A is a broad-range protease inhibitor. Fetuin-A inhibition of meprin activity was 40 times weaker than that of meprin activity. Therefore, we tested cystatin C, a protein structurally closely related to fetuin-A. Indeed, cystatin C was an inhibitor for human meprin (K(i) = 8.5 × 10(-6) M) but, interestingly, not for meprin . Thus, the identification of fetuin-A and cystatin C as endogenous proteolytic regulators of meprin activity broadens our understanding of the proteolytic network in plasma.

Role and regulation of c-KIT gene expression in tumor growth and metastasis of human melanoma

The purpose of this study was to investigate the role of the c-KIT receptor in the progression of human melanoma and the mechanism(s) for the regulation of c-KIT gene expression in human melanoma.^ The molecular changes associated with the transition of melanoma cells from radial growth phase (RGP) to vertical growth phase (VGP) (metastatic phenotype) are not well-defined. Expression of the tyrosine-kinase receptor c-KIT progressively decreases during local tumor growth and invasion of human melanomas. To provide direct evidence that the metastasis of human melanoma is associated with the loss of c-KIT expression, highly metastatic A375SM cells, which express very low or undetectable levels of c-KIT, were tranduced with the human c-KIT gene. We demonstrated that enforced c-KIT expression in highly metastatic human melanoma cells significantly suppressed their tumorigenicity and metastatic propensity in nude mice. In addition, we showed that the ligand for c-KIT, SCF, induces apoptosis in human melanoma cells expressing c-KIT under both in vitro and in vivo conditions. These results suggest that loss of c-KIT receptor may allow malignant melanoma cells to escape SCF/c-KIT-mediated apoptosis, thus contributing to tumor growth and eventually metastasis.^ Furthermore, we investigated the possible mechanism(s) for the down-regulation of c-KIT gene expression in malignant melanoma. Sequence analysis of the c-KIT promoter indicated that this promoter contains several consensus binding-site sequences including three putative AP2 and two Myb sites. Although Myb was shown to be associated with c-KIT expression in human hemotopoietic cells, we found no correlation between c-KIT expression and Myb expression in human melanoma cell lines. In contrast, we showed that c-KIT expression directly correlates with expression of AP2 in human melanoma cells. We found that highly metastatic cells do not express the transcription factor AP2. Expression of AP2 in A375SM cells (c-KIT-negative and AP2-negative) was enough to restore luciferase activity driven by the c-KIT promoter in a dose-dependent manner. On the other hand, co-expression of the dominant-negative form of AP2 (AP2B) in Mel-501 cells (c-KIT-positive and AP2-positive) resulted in two-fold reduction in luciferase activity. Electrophoretic mobility shift assays revealed that the c-KIT promoter contains functional AP2 binding sites which could associate with AP2 protein. Endogenous c-KIT gene expression levels were elevated in AP2 stably-transfected human melanoma A375SM cells. Expression of exogenous AP2 in A375SM cells inhibited their tumorigenicity and metastatic potential in nude mice. The c-KIT ligand, SCF, also induced apoptosis in the AP2 stably-transfected A375SM cells. The identification of AP2 as an important regulator for c-KIT expression suggests that AP2 may have tumor growth and metastasis inhibitory properties, possibly mediated through c-KIT/SCF effects on apoptosis of human melanoma cells. Since AP2 binding sites were found in the promoters of other genes involved in the progression of human melanoma, such as MMP2 (72 kDa collagenase), MCAM/MUC18 and P21/WAF-1, our findings suggest that loss of AP2 expression might be a crucial event in the development of malignant melanoma. ^

The AIDS crisis in two American cities [microform] : hearings before a subcommittee of the Committee on Government Operations, House of Representatives, One Hundredth Congress, first session, September 18 and November 23, 1987.

CIS Microfiche Accession Numbers: CIS 89 H401-24

Employment and the Social Economy. EU Funding Opportunities for Developing Human Resources

The paper examines the role of EU cohesion policy in the field of human resources development and improving conditions for employment. The main objective of the analysis is to present a comprehensive picture about funding opportunities in connection with financing the activities of organisations of the social economy. As a background, the study stresses that the success of the European integration process depends to a great extent on the strength of economic and social cohesion between EU member states and regions. In order to create conditions for sustainable and balanced growth with social inclusion, there is a need to enhance the competitiveness of less developed regions combating the difficulties of structural change, and to improve their development prospects. To achieve this aim, one of the most important fields is to improve human resources. The paper points out, that EU cohesion policy has a crucial role in reducing disparities. After a general introduction to the EU level regional policy funding, the study focuses on the activities supported by the European Social Fund (ESF). The next part of the study deals with the possible types of the social economy projects and problems of self-financing. The author emphasises that social innovation emerges where State and markets fail to deliver for society (theory of non-profit/third sector) but not just to fix or replace them. The author concludes that these projects require state subsidies (official grants) at the beginning, but at the same time they can generate income. In this respect they follow same economic goals as other market actors, however, the crucial difference is that their main goal is not to make high profits for the owners. In the last part, as a concrete case study, the paper concentrates on the priorities of the Hungarian development plan in relation to social renewal. The author explains the priorities and fields of interventions of the social renewal programme. Finally, the chapter deals with the recent changes in the Hungarian employment policy and related measures supported by the European Social Fund. The chapter concludes that several employment programmes, projects for the development of social economy and programmes assisting the spreading of voluntariness and the training of volunteers have been launched with the co-financing of ESF.

Variables affecting the collection and preservation of human scent components through instrumental and biological evaluations

In certain European countries and the United States of America, canines have been successfully used in human scent identification. There is however, limited scientific knowledge on the composition of human scent and the detection mechanism that produces an alert from canines. This lack of information has resulted in successful legal challenges to human scent evidence in the courts of law. ^ The main objective of this research was to utilize science to validate the current practices of using human scent evidence in criminal cases. The goals of this study were to utilize Headspace Solid Phase Micro Extraction Gas Chromatography Mass Spectrometry (HS-SPME-GC/MS) to determine the optimum collection and storage conditions for human scent samples, to investigate whether the amount of DNA deposited upon contact with an object affects the alerts produced by human scent identification canines, and to create a prototype pseudo human scent which could be used for training purposes. ^ Hand odor samples which were collected on different sorbent materials and exposed to various environmental conditions showed that human scent samples should be stored without prolonged exposure to UVA/UVB light to allow minimal changes to the overall scent profile. Various methods of collecting human scent from objects were also investigated and it was determined that passive collection methods yields ten times more VOCs by mass than active collection methods. ^ Through the use of polymerase chain reaction (PCR) no correlation was found between the amount of DNA that was deposited upon contact with an object and the alerts that were produced by human scent identification canines. Preliminary studies conducted to create a prototype pseudo human scent showed that it is possible to produce fractions of a human scent sample which can be presented to the canines to determine whether specific fractions or the entire sample is needed to produce alerts by the human scent identification canines. ^

Variables Affecting the Collection and Preservation of Human Scent Components through Instrumental and Biological Evaluations

In certain European countries and the United States of America, canines have been successfully used in human scent identification. There is however, limited scientific knowledge on the composition of human scent and the detection mechanism that produces an alert from canines. This lack of information has resulted in successful legal challenges to human scent evidence in the courts of law. The main objective of this research was to utilize science to validate the current practices of using human scent evidence in criminal cases. The goals of this study were to utilize Headspace Solid Phase Micro Extraction Gas Chromatography Mass Spectrometry (HS-SPME-GC/MS) to determine the optimum collection and storage conditions for human scent samples, to investigate whether the amount of DNA deposited upon contact with an object affects the alerts produced by human scent identification canines, and to create a prototype pseudo human scent which could be used for training purposes. Hand odor samples which were collected on different sorbent materials and exposed to various environmental conditions showed that human scent samples should be stored without prolonged exposure to UVA/UVB light to allow minimal changes to the overall scent profile. Various methods of collecting human scent from objects were also investigated and it was determined that passive collection methods yields ten times more VOCs by mass than active collection methods. Through the use of polymerase chain reaction (PCR) no correlation was found between the amount of DNA that was deposited upon contact with an object and the alerts that were produced by human scent identification canines. Preliminary studies conducted to create a prototype pseudo human scent showed that it is possible to produce fractions of a human scent sample which can be presented to the canines to determine whether specific fractions or the entire sample is needed to produce alerts by the human scent identification canines.

Capital 2.0 capital formation and legal risk in a new global economic order from fiat to exit: including case studies of the proposed transatlantic trade and investment partnership between the United States and the European Union and the financing relation between the United States and the People’s Republic of China

Following the intrinsically linked balance sheets in his Capital Formation Life Cycle, Lukas M. Stahl explains with his Triple A Model of Accounting, Allocation and Accountability the stages of the Capital Formation process from FIAT to EXIT. Based on the theoretical foundations of legal risk laid by the International Bar Association with the help of Roger McCormick and legal scholars such as Joanna Benjamin, Matthew Whalley and Tobias Mahler, and founded on the basis of Wesley Hohfeld’s category theory of jural relations, Stahl develops his mutually exclusive Four Determinants of Legal Risk of Law, Lack of Right, Liability and Limitation. Those Four Determinants of Legal Risk allow us to apply, assess, and precisely describe the respective legal risk at all stages of the Capital Formation Life Cycle as demonstrated in case studies of nine industry verticals of the proposed and currently negotiated Transatlantic Trade and Investment Partnership between the United States of America and the European Union, TTIP, as well as in the case of the often cited financing relation between the United States and the People’s Republic of China. Having established the Four Determinants of Legal Risk and its application to the Capital Formation Life Cycle, Stahl then explores the theoretical foundations of capital formation, their historical basis in classical and neo-classical economics and its forefathers such as The Austrians around Eugen von Boehm-Bawerk, Ludwig von Mises and Friedrich von Hayek and most notably and controversial, Karl Marx, and their impact on today’s exponential expansion of capital formation. Starting off with the first pillar of his Triple A Model, Accounting, Stahl then moves on to explain the Three Factors of Capital Formation, Man, Machines and Money and shows how “value-added” is created with respect to the non-monetary capital factors of human resources and industrial production. Followed by a detailed analysis discussing the roles of the Three Actors of Monetary Capital Formation, Central Banks, Commercial Banks and Citizens Stahl readily dismisses a number of myths regarding the creation of money providing in-depth insight into the workings of monetary policy makers, their institutions and ultimate beneficiaries, the corporate and consumer citizens. In his second pillar, Allocation, Stahl continues his analysis of the balance sheets of the Capital Formation Life Cycle by discussing the role of The Five Key Accounts of Monetary Capital Formation, the Sovereign, Financial, Corporate, Private and International account of Monetary Capital Formation and the associated legal risks in the allocation of capital pursuant to his Four Determinants of Legal Risk. In his third pillar, Accountability, Stahl discusses the ever recurring Crisis-Reaction-Acceleration-Sequence-History, in short: CRASH, since the beginning of the millennium starting with the dot-com crash at the turn of the millennium, followed seven years later by the financial crisis of 2008 and the dislocations in the global economy we are facing another seven years later today in 2015 with several sordid debt restructurings under way and hundred thousands of refugees on the way caused by war and increasing inequality. Together with the regulatory reactions they have caused in the form of so-called landmark legislation such as the Sarbanes-Oxley Act of 2002, the Dodd-Frank Act of 2010, the JOBS Act of 2012 or the introduction of the Basel Accords, Basel II in 2004 and III in 2010, the European Financial Stability Facility of 2010, the European Stability Mechanism of 2012 and the European Banking Union of 2013, Stahl analyses the acceleration in size and scope of crises that appears to find often seemingly helpless bureaucratic responses, the inherent legal risks and the complete lack of accountability on part of those responsible. Stahl argues that the order of the day requires to address the root cause of the problems in the form of two fundamental design defects of our Global Economic Order, namely our monetary and judicial order. Inspired by a 1933 plan of nine University of Chicago economists abolishing the fractional reserve system, he proposes the introduction of Sovereign Money as a prerequisite to void misallocations by way of judicial order in the course of domestic and transnational insolvency proceedings including the restructuring of sovereign debt throughout the entire monetary system back to its origin without causing domino effects of banking collapses and failed financial institutions. In recognizing Austrian-American economist Schumpeter’s Concept of Creative Destruction, as a process of industrial mutation that incessantly revolutionizes the economic structure from within, incessantly destroying the old one, incessantly creating a new one, Stahl responds to Schumpeter’s economic chemotherapy with his Concept of Equitable Default mimicking an immunotherapy that strengthens the corpus economicus own immune system by providing for the judicial authority to terminate precisely those misallocations that have proven malignant causing default perusing the century old common law concept of equity that allows for the equitable reformation, rescission or restitution of contract by way of judicial order. Following a review of the proposed mechanisms of transnational dispute resolution and current court systems with transnational jurisdiction, Stahl advocates as a first step in order to complete the Capital Formation Life Cycle from FIAT, the creation of money by way of credit, to EXIT, the termination of money by way of judicial order, the institution of a Transatlantic Trade and Investment Court constituted by a panel of judges from the U.S. Court of International Trade and the European Court of Justice by following the model of the EFTA Court of the European Free Trade Association. Since the first time his proposal has been made public in June of 2014 after being discussed in academic circles since 2011, his or similar proposals have found numerous public supporters. Most notably, the former Vice President of the European Parliament, David Martin, has tabled an amendment in June 2015 in the course of the negotiations on TTIP calling for an independent judicial body and the Member of the European Commission, Cecilia Malmström, has presented her proposal of an International Investment Court on September 16, 2015. Stahl concludes, that for the first time in the history of our generation it appears that there is a real opportunity for reform of our Global Economic Order by curing the two fundamental design defects of our monetary order and judicial order with the abolition of the fractional reserve system and the introduction of Sovereign Money and the institution of a democratically elected Transatlantic Trade and Investment Court that commensurate with its jurisdiction extending to cases concerning the Transatlantic Trade and Investment Partnership may complete the Capital Formation Life Cycle resolving cases of default with the transnational judicial authority for terminal resolution of misallocations in a New Global Economic Order without the ensuing dangers of systemic collapse from FIAT to EXIT.

Small-scale fishing in Central American indigenous people: governance, tenure and sustainable management of marine resources

This research develops four case studies on small-scale fisheries in Central America located within indigenous territories. The ngöbe Bugle Conte Burica Territory in the south of Costa Rica, the Garífuna territory in nueva Armenia Honduras, the Rama territory in Nicaragua and the ngöbe Bugle territory in Bocas del Toro, Panamá. This is one of the first studies focusing on indigenous territories, artisanal fisheries and SSF guidelines. The cases are a first approach to discussing and analyzing relevant social and human rights issues related to conservation of marine resources and fisheries management in these territories. The cases discussed between other issues of interest, the relationships between marine protected areas under different governance models and issues related to the strengthening of the small-scale fisheries of these indigenous populations and marine fishing territories. They highlight sustainability, governance, land tenure and access to fishing resources, gender, traditional knowledge importance and new challenges as climate change.

The central role of human resource management in the search for sustainable organizations

The aim of this article is to present the main contributions of human resource management to develop sustainable organizations. The relationship between human resources and organizational sustainability, which is based on economical, social and environmental performance, involves some important aspects concerning management such as innovation, cultural diversity and the environment. The integration of items from the triple bottom line approach leads to developing a model based on a strategic and central posture of human resource management. Based on this model, propositions and recommendations for future research on this theme are presented.

Limited Ca(2+) and PKA-pathway dependent neurogenic differentiation of human adult mesenchymal stem cells as compared to fetal neuronal stem cells

The ability of mesenchymal stem cells to generate functional neurons in culture is still a matter of controversy. In order to assess this issue, we performed a functional comparison between neuronal differentiation of human MSCs and fetal-derived neural stem cells (NSCs) based on morphological, immunocytochemical, and electrophysiological criteria. Furthermore, possible biochemical mechanisms involved in this process were presented. NF200 immunostaining was used to quantify the yield of differentiated cells after exposure to CAMP. The addition of a PKA inhibitor and Ca(2+) blockers to the differentiation medium significantly reduced the yield of differentiated cells. Activation of CREB was also observed on MSCs during maturation. Na(+)-, K(+)-, and Ca(2+)-voltage-dependent currents were recorded from MSCs-derived cells. In contrast, significantly larger Na(+) currents, firing activity, and spontaneous synaptic currents were recorded from NSCs. Our results indicate that the initial neuronal differentiation of MSCs is induced by CAMP and seems to be dependent upon Ca(2+) and the PKA pathway. However, compared to fetal neural stem cells, adult mesenchymal counterparts are limited in their neurogenic potential. Despite the similar yield of neuronal cells, NSCs achieved a more mature functional state. Description of the underlying mechanisms that govern MSCs` differentiation toward a stable neuronal phenotype and their limitations provides a unique opportunity to enhance our understanding of stem cell plasticity. (C) 2009 Elsevier Inc. All rights reserved.