Genes invoked in the ovarian transition to menopause

Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene–protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function

Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression

The study of T regulatory cells (T reg cells) has been limited by the lack of specific surface markers and an inability to define mechanisms of suppression. We show that the expression of CD39/ENTPD1 in concert with CD73/ecto-5′-nucleotidase distinguishes CD4+/CD25+/Foxp3+ T reg cells from other T cells. These ectoenzymes generate pericellular adenosine from extracellular nucleotides. The coordinated expression of CD39/CD73 on T reg cells and the adenosine A2A receptor on activated T effector cells generates immunosuppressive loops, indicating roles in the inhibitory function of T reg cells. Consequently, T reg cells from Cd39-null mice show impaired suppressive properties in vitro and fail to block allograft rejection in vivo. We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation

Motivational conditions of successful corporate social responsibility (CSR) actions in form of cross sector collaborations in international health

It is clearly of paramount importance to secure both short-term and long-term provision and access to drugs and healthcare services in order to accomplish a substantial impact on public health in any country. Nevertheless, there are millions of people, especially in the developing world, that have no or limited access to such pharmaceutics and services. Faced with the situation, some important cross-sector efforts that make drugs and services available through the engagement of private for profit firms in corporate social responsibility (CSR) have been launched in the international health scene. Yet CSR and civil involvement in cross-sector collaborations also open the door to exploitation and opportunistic behavior. Hence, it is essential to learn more about what makes cross-sector partnerships succeed, while developing a framework that supports sustainable partnerships in a morally and ethically sound context. Furthermore, as cross-collaborations do not simply ÒhappenÓ, but are rather built, and since little information is available on the necessary conditions leading to their successful formation, governance and management - despite the number of collaborations that have been established in the past decades - further research is urgently called for. The aim of this work is to investigate how cross-sector collaborations, that attempt to improve access to healthcare in the developing world, could be strengthened and improved through the involvement of firms in CSR. By assessing motivational factors and skills that allow a favorable collaborative culture and value creation to the company through such collaborations, partnerships could be strengthened and their outcomes maximized. Through a longitudinal case study, involving for profit businesses in Germany and Switzerland, an established NGO in Ethiopia, as well as the Tigray Regional Health Bureau of the Ethiopian Ministry of Health, we were able to identify initial motivational factors that lead to the engagement of firms in CSR in the form of cross-sector collaborations, as well as motivational factors and conditions which promote value creation and long-term commitment of organizations to CSR. Using multiple qualitative methods, we were able to identified three motivational cornerstones that allow a positive output in form of a motivating collaborative culture and intangible asset creation, namely 1) the need of help and a mutual value exchange approach, with value creation as a primary motivation for embarking in the project 2) alignment between collaboration-/project-mission and core activity/mission of the participating businesses, and strategic congruency between participating parties, as incentives, and 3) the implementation of sound motivational competencies such as catalyzing-, leadership- and management- skills. When these cornerstones are in place, an environment that favors intangible asset creation and positive outcome, as well as sustainability, can evolve. This favorable environment, or TIES-culture, is characterized by Trusting relationships between the various parties involved, Identification and emotional connection with the cause, Empowering environment that stimulates learning, as well as a Successful organizational culture that feeds gratification and satisfaction. The TIES-culture is an important intangible asset per se, yet the defined collaborative culture also supports further intangible value creation in form of human capital, information capital and organizational capital, and the consequent ability of an organization to mobilize and sustain processes of change that are required to execute its strategy. As the global economy is changing and shifting from manufacturing to a service oriented economy, intangible assets and intellectual capital have become increasingly important resources for a companyÕs, organizationÕs or partnershipÕs success and value creation, especially in the healthcare industry. Intangible assets can support the improving of business and collaborative processes and performance, and finally be converted into tangible outcomes in form of improved health and other social outcomes, revenue growth and in form of cost reduction. Building on the Balanced Score Card by Kaplan and Norton, and based on data obtained through this case study, we were able to develop a tool (The Collaboration Scorecard) that adapts to the specific setting of collaborations and CSR, and that allows a systematic analysis of input, output and outcome, and the correlation between these components and the tangible and intangible value created to organizations through cross-sector collaborations. In addition, it can serve as a preliminary evaluation tool and guide for businesses, immersed in cross-sector collaborations, in how to create future value through investment in customers, suppliers, employees, processes, technology, and innovation. In sum, in order to accomplish a long-term impact on global public health, it is of great importance to encourage the commitment of private firms to CSR and to a stronger collaboration between businesses, NGOs and governments involved in the international health sector. Based on the knowledge gained through this explorative study, motivational frameworks and strategies that maximize both tangible and intangible asset creation through cross-sector collaborations may be developed. Businesses may capitalized on the intangible assets created through cross- sector collaborations, and the ensuing value creation, for all participants involved, may encourage stronger civil involvement in public health, especially when governments fail to provide public goods and services in the international health sector

Arterial territory-specific phosphorylated retinoblastoma protein species and CDK2 promote differences in the vascular smooth muscle cell response to mitogens

Despite recent advances in medical procedures, cardiovascular disease remains a clinical challenge and the leading cause of mortality in the western world. The condition causes progressive smooth muscle cell (SMC) dedifferentiation, proliferation, and migration that contribute to vascular restenosis. The incidence of disease of the internal mammary artery (IMA), however, is much lower than in nearly all other arteries. The etiology of this IMA disease resistance is not well understood. Here, using paired primary IMA and coronary artery SMCs, serum stimulation, siRNA knockdowns, and verifications in porcine vessels in vivo, we investigate the molecular mechanisms that could account for this increased disease resistance of internal mammary SMCs. We show that the residue-specific phosphorylation profile of the retinoblastoma tumor suppressor protein (Rb) appears to differ significantly between IMA and coronary artery SMCs in cultured human cells. We also report that the differential profile of Rb phosphorylation may follow as a consequence of differences in the content of cyclin-dependent kinase 2 (CDK2) and the CDK4 phosphorylation inhibitor p15. Finally, we present evidence that siRNA-mediated CDK2 knockdown alters the profile of Rb phosphorylation in coronary artery SMCs, as well as the proliferative response of these cells to mitogenic stimulation. The intrinsic functional and protein composition specificity of the SMCs population in the coronary artery may contribute to the increased prevalence of restenosis and atherosclerosis in the coronary arteries as compared with the internal mammary arteries

doi:10.1093/nar/gkl387 Genes invoked in the ovarian transition to menopause

Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the agingspecific decline in ovarian function are almost completely unknown. To provide the first gene– protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function

DNA array to confirm differential gene expression in young and old ovaries

<p><b>Copyright information:</b></p><p>Taken from "Genes invoked in the ovarian transition to menopause"</p><p>Nucleic Acids Research 2006;34(11):3279-3287.</p><p>Published online 28 Jun 2006</p><p>PMCID:PMC1904106.</p><p>© 2006 The Author(s)</p> Identical DNA array membranes containing probes for 440 aging-related mouse genes were probed with individual P-labeled cDNA libraries prepared from () young and () aged ovaries. Lower panels of () and () show an enlargement of the framed membrane portions in the upper panels. Matrix overlay maps the position of the nucleotides for each gene. Positions 62, Leptin; 79, CD36 antigen; 117, unknown EST are examples of decreased levels with aging. Positions 58, peroxisome proliferators activated receptor-a; 105, transcription factor NFκB are examples of increased levels with aging

Western blots of total protein lysates from young and old mouse ovaries

<p><b>Copyright information:</b></p><p>Taken from "Genes invoked in the ovarian transition to menopause"</p><p>Nucleic Acids Research 2006;34(11):3279-3287.</p><p>Published online 28 Jun 2006</p><p>PMCID:PMC1904106.</p><p>© 2006 The Author(s)</p> () Proteins with reduced content in old (o) ovaries compared with young ovaries (y); () proteins with higher level in young ovaries; and () no change in protein content. Proteins were visualized with protein-specific antibodies as indicated at the left of the panels. The size (kDa) of the protein marker is indicated at the right of the panels. All lanes received 100 μg of total ovarian lysate. The immunological reactions are visualized by HSP-coupled secondary antibodies