Hematopoietic stem cells and aging

Hematopoiesis is a process by which a single cell--called a hematopoietic stem cell (HSC)--has the proliferative potential to give rise to all of the major lineages of blood and immune cells. Stem cells can undergo both symmetric division, which results in two copies of the parent stem cell, and asymmetric division, which results in self-renewal of the parent stem cell as well as production of a daughter cell that is capable of differentiating along a specific lineage. A number of different elements of HSC replication change with age, even though these transformations do not appear to result in hematopoietic deficiencies under normal circumstances. In this Perspective, the author discusses these age-related alterations.     

Oxidative mutagenesis, mismatch repair, and aging

A PubMed search for the term "oxidative stress" yields over 29,000 articles published on the subject over the past 10 years; more than 2000 of these articles also include the term "aging" in their title or abstract. Many theories of aging predict causal roles for oxidative stress in the myriad of pathological changes that occur as a function of age, including an increasing propensity to develop cancer. A possible link between aging and cancer is the induction and accumulation of somatic mutations caused by oxidative stress. This Review focuses on small mutational events that are induced by oxidative stress and the role of mismatch repair (MMR) in preventing their formation. It also discusses a possible inhibitory effect of oxidative stress on MMR. We speculate that a synergistic interaction between oxidative damage to DNA and reduced MMR levels will, in part, account for an accumulation of small mutational events, and hence cancer, with aging.     

Les promesses des cellules souches. Scientifiques, familles et santé publique dans la controverse autour des stem cells aux USA

This article describes the impact of the contested properties of stem cells in the United States. Starting from the limitations on stem cell research that the current Bush administration imposed, it is possible to follow the mobilizations of various levels of us politics, each of them being articulated around exclusive properties of the stem cell. Ranging from the role of the family in the biomedical research decisions to the threat of a disintegration of the Union, stem cells question the American body politic.     

Realms,subfields, and perspectives: On the differentiation and fragmentation of sociology

This article proposes a heuristic classification of intradisciplinary structure and applies that scheme to the current debate over the relationship between the proliferation of subfields and disciplinary fragmentation in sociology. It is argued here that the fragmentation of sociology is caused by the multiplication of competing perspectives rather than by the differentiation of fields of specialization. While competition among perspectives reflects disagreements among sociologists on what their subject matter should be and how to approach it, the proliferation of subfields is generally a result of disciplinary progress.     

Acquired immunity: immunosenescence and physical activity

Several lines of evidence indicate that infectious diseases, cancer, and autoimmune disorders occur more frequently in elderly people, thus suggesting that altered function of immune organs and cells, such as thymus and T and B lymphocytes are of primary importance in the pathogenesis of these diseases. Furthermore, old subjects are less responsive to vaccine than younger because of immune changes. The most common changes accompanying the adaptive immune system include decrement of T and B cells proliferation, repertoire degeneracy, increase of the memory cell type, decreased numbers of naive cells, and shift from T helper₁ (Th1) to T helper₂ (Th2) response. Regular exercise in the elderly may improve the alterations in acquired immunity which follow the physiological process of aging, allowing a major resistance against external pathogens and a better quality of life.     

Dear old dad

The origin and frequency of spontaneous mutations that occur with age in humans have been a topic of intense discussion. The mechanisms by which spontaneous mutations arise depend on the parental germ line in which a mutation occurs. In general, paternal mutations are more likely than maternal mutations to be base substitutions. This is likely due to the larger number of germ cell divisions in spermatogenesis than in oogenesis. Maternal mutations are more often chromosomal abnormalities. Advanced parental age seems to influence some mutations, although it is not a factor in the creation of others. In this review, we focus on patterns of paternal bias and age dependence of mutations in different genetic disorders, and the various mechanisms by which these mutations arise. We also discuss recent data on age and the frequency of these mutations in the human male germ line and the impact of these data on this field of research.     

Adult cardiac stem cells--where do we go from here?

A potential treatment for cardiovascular disease involves the transplantation of a patient's bone marrow stem cells into the heart of that same patient. In order to maximize the potential benefits to select patient populations, the continued clinical development of this technology will require a comprehensive understanding of the role(s) of the transplanted cells in the repair of damaged heart tissue as well as an understanding of which types of cardiac injury can be repaired by this approach. The widespread application of cardiovascular stem cell therapies, however, will likely be based on pharmacological approaches to enhance the capacity of endogenous bone marrow stem cells to provide for the replacement of cardiac muscle and vascular cells after myocardial injury.     

血管生成素通过ERK信号通路促进HeLa细胞的增殖

目的通过细胞外信号调节激酶（extracellularregulatedproteinkinases,ERK）通路及NF-xB信号途径探讨血管生成素（angiogenin,Ang）对HeLa细胞的促增殖及抗凋亡作用机制。方法用不同浓度的重组人Ang刺激HeLa细胞,MTr法分析Ang对HeLa细胞的促增殖作用,蛋白质印迹实验检测ERK信号通路相关分子的表达情况。U0126抑制ERK信号通路,检测Ang诱导的ERKl／2的磷酸化及c—myc的表达情况,同时检测Ang对细胞增殖的影响。敲低Ang的表达,检测细胞的凋亡情况。双荧光素酶报告基因检测Ang对NF-KB报告基因的激活。蛋白水平检测Ang刺激的HeLa细胞后,NF—KB通路相关分子的表达。结果Ang能促进HeLa细胞增殖,ERKl／2的磷酸化水平及c—myc的表达随重组人Ang浓度的升高而增加。U0126能抑制Ang诱导的ERKI／2的磷酸化、c—myc的上调及细胞的增殖。Ang的低表达促进HeLa细胞的凋亡,但不影响NF-KB报告基因的激活及NF—KB通路上相关分子的表达。结论Ang能够促进HeLa细胞增殖,并通过活化ERK通路促进细胞的增殖,但其抑凋亡作用与NF-KB通路无关。     

Stem Cell Research and Biopsychosocial Perspectives From the Sciences,Government, and Community

Stem cell research is a fairly new technological advancement that has been accompanied by a wide range of support and scrutiny. On February 22, 1997, Dolly, the sheep, was successfully cloned in Scotland, while controversy erupted over the moral, ethical, and social implications of creating life. Though many agree that using human embryos is morally acceptable, the United States, Canada, Australia, United Kingdom, and European countries have passed legislation limiting or prohibiting stem cell research. This article considers the biopsychosocial benefits and potential hazards of stem cell research and how this research may affect social work practice.     

La tournée des facteurs Normes gestionnaires, régulation collective et stratégies d’activité

The work of mailmen is mainly defined by the delivery routes to which they are assigned. Since this special organization of work grants them broad autonomy, the processes for delimiting, defining, and conducting routes must be analyzed by taking into account observations from three levels. The first one focuses on the French Post Office’s managerial standards, which, though increasingly determined by objectives for making a profit, have little impact on mail deliverers’ activities. The second centers around this occupational group’s own regulations, which stem from a hierarchy based on seniority and control over mail delivery and routes. The third level of observation takes into view the strategies for delivering mail that postmen adopt on their routes. These strategies reflect different relations to managerial objectives and to customers; and they reveal contrasting conceptions of the job of delivering mail. Emphasis is laid on the fact that the situations for working at lower levels in the service sector cannot be separated from the factors defining and organizing these situations.     

“Mail carriers’ routes: Managerial standards,collective regulation and work activity strategies”

The work of mailmen is mainly defined by the delivery routes they are assigned. Since this special organization of work grants them broad autonomy, the processes for delimiting, defining, and conducting routes, must be analyzed by taking into account observations from three levels. The first one focuses on the French Post Office’s managerial standards, though, increasingly determined by objectives for making a profit, have little impact on mail deliverer’s activities. The second centers around this occupational group’s own regulation which stem from a hierarchy based on seniority and control over mail delivery and routes. The third level of observation takes into view the strategies for delivering mail that postmen adopt on their routes. These strategies reflect different relations to managerial objectives and to consumers; and they reveal contrasting conceptions of the job of delivering mail. Emphasis is laid on the fact that the situations for working at lower levels in the service sector cannot be separated from the factors defining and organizing these situations.     

Single-cell antisense RNA amplification and microarray analysis as a tool for studying neurological degeneration and restoration

Neurodegenerative diseases typically affect subpopulations of neurons. Characterizing these vulnerable cells and identifying the factors that make them susceptible to damage while neighboring cells remain resistant are essential to the understanding of molecular pathogenesis that underlies neurodegenerative diseases. Classically, molecular analysis of the central nervous system involves the identification and isolation of an anatomic region of interest; next, the relevant tissue is pulverized, and the resulting homogenate is analyzed. Although this method provides useful data, its effectiveness diminishes when used in areas of high cellular diversity or in instances in which one cell type is lost as a consequence of selective cell death or quiescence. A technique that affords the ability to assess molecular events in a very precise anatomical site would provide a powerful tool for this research discipline. In this review, we discuss the amplification of messenger RNA from single neural cells and the subsequent use of the RNA to probe DNA microarrays in an effort to create cell-specific molecular profiles. Specifically, recent work in single-cell expression profiling in Alzheimer's and Huntington's diseases is discussed. We also review some new work with neural stem cells and their application to restorative neurobiology. Finally, we discuss the use of cell-specific molecular profiles to better understand the basics of neuronal cell biology.     

How social media transform migrant networks and facilitate migration

We argue that social media are not only new communication channels in migration networks, but also that they actively transform the nature of these networks and thereby facilitate migration. Despite some limitations, which stem from the ‘digital divide’ and the lower trustworthiness of virtual ties, qualitative data reveal four relevant ways in which social media facilitate international migration. First, they enhance the possibilities of maintaining strong ties with family and friends. Second, they address weak ties that are relevant to organizing the process of migration and integration. Third, they establish a new infrastructure consisting of latent ties. Fourth, they offer a rich source of insider knowledge on migration that is discrete and unofficial. This makes potential migrants ‘streetwise’ when undertaking migration. Based on these empirical findings we conclude that social media are transforming migration networks and thereby lowering the threshold for migration.     

“Spokes in the wheel” and how policy gains can diversify a social movement

ABSTRACT

Activists often use their resources to pursue protective legislation, like anti-discrimination or environmental protection laws, and the results are often compromised versions of what they wanted. This process of political institutionalization requires ongoing and robust mobilization to strengthen these resulting policies or prevent them from being rescinded all together. Therefore, to understand the pros and cons of political institutionalization we must understand the recursive effects between policy reform and consequent mobilization. Quantitative and qualitative data on the animal advocacy movement, a movement existing for over a century, are used to explore the effects of policy gains on consequent mobilization and explore whether policy gains were followed by de-escalation of protest forms. The findings indicate that policy gains for animal welfare do not de-escalate mobilization, both in terms of the use of disruptive collective action and proliferation of organizations. The article explores the ways that infighting over the terms of policy reform may be an important factor in diversifying the movement.     

Cyclin-dependent kinase 5--a neuronal killer?

In dividing cells, cyclin-dependent kinases (Cdks) are cell cycle-associated protein kinases that regulate proliferation, differentiation, senescence, and apoptosis. In neurons that no longer divide, deregulation of Cdks, especially Cdk5, occurs in many neurological disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Cdk5 is a unique member of the Cdk family because it does not play a critical role in cell cycle progression, and it is not activated by a cyclin. Instead, Cdk5 normally is activated by the regulatory protein p35. This Cdk5/p35 activity has emerged as an important regulator of proper development of the mammalian central nervous system. In vitro studies suggest that aberrant activation of Cdk5 by an endogenous truncated version (p25) of p35 might be a key event in the process of neurodegeneration. One enzyme responsible for cleavage of p35 to form p25 is calpain, a calcium-activated protease that has been shown to be involved in neuronal cell death. Recent studies provided important in vivo evidence that hyperactivation and redistribution of Cdk5 by p25 plays an essential role in the phosphorylation of "pathological" substrates (such as tau) and the cell death of neurons in experimental models of AD and PD. Because amyloid beta peptide, the primary neurotoxic component of amyloid plaques in AD, has been shown to increase the conversion of p35 to p25, aberrant activation of Cdk5 by p25 might be a pathway connecting amyloid beta toxicity to tau hyperphosphorylation in AD.     

Mouse and human cells versus oxygen

Mice and humans are at opposite ends of the mammalian spectrum of longevity. A major question in biology is whether this difference can be accounted for by differences in the properties of cells from these two species. A new publication from Judith Campisi's lab reports that human cells in culture are more resistant than mouse cells to the damaging effects of 20% oxygen. The greater burden of DNA damage sustained by mouse cells causes them to rapidly enter a phase of culture in which most cells enter permanent growth arrest (replicative senescence). However, some mouse cells usually escape from senescence and then grow into an immortal cell line. This never happens in human fibroblast cell cultures. Human cells also eventually enter replicative senescence in culture, but this phenomenon is caused by shortening of telomeres and not by DNA damage of the type responsible for mouse cell senescence. Human fibroblasts never spontaneously escape from senescence. This Perspective reviews differences between mouse and human cells that could account for these differences in behavior. Some evidence indicates that human cells are generally more resistant than mouse cells to oxidative damage to DNA, but more needs to be done to confirm this finding and to understand the underlying mechanisms. Whether or not there are differences in the amount of DNA damage caused by oxygen or in the early phase of repair, there may be important differences in the later consequences of DNA damage. Mouse cells appear to be able to continue to divide with DNA damage that has not been repaired or has been misrepaired, and becomes fixed in the form of chromosomal abnormalities. The checkpoints that cause cells to stop dividing when chromosomes develop abnormalities (aberrations or shortened telomeres) appear to operate more efficiently in human cells. Much more work is needed to understand the basis for these differences and the implications for aging and cancer.     

Improving the well-being of couples facing cancer: a review of couples-based psychosocial interventions

The purpose of this review article is to assess the available scientific evidence on the effects of couples-based psychosocial interventions for couples when one spouse faces cancer. For the present study, we conducted an extensive search of three electronic databases using a comprehensive search strategy. The literature search identified 14 studies evaluating couples intervention where one partner is facing cancer. Among them, eight studies concluded there was overall improvement for patients and eight studies reported overall improvement for partners, whereas an additional five studies showed partial improvement for patients and three demonstrated partial improvements for partners. Taken in the aggregate, these studies illustrated partial effectiveness--most had some positive results--but with clear limitations in terms of how many aspects of psychosocial well-being changed, lack of equal effectiveness for both patients and their partners, or limited maintenance of improvements over time, a common concern with brief psychosocial interventions. Although couples-based interventions may facilitate emotional support and dyadic coping, how these psychosocial interventions should be delivered, at what point in the illness and treatment they should be delivered, and how long they should continue remain as future challenges.     

Vaginal Dryness and Beyond: The Sexual Health Needs of Women Diagnosed With Metastatic Breast Cancer

While research on the sexual health of women with early stage cancer has grown extensively over the past decade, markedly less information is available to support the sexual health needs of women diagnosed with advanced breast cancer. Semistructured interviews were conducted with 32 women diagnosed with metastatic breast cancer (ages 35 to 77) about questions they had concerning their sexual health and intimate relationships. All participants were recruited from a comprehensive cancer center at a large Midwestern university. Three themes were examined: the role of sexual activity and intimate touch in participants' lives, unmet information needs about sexual health, and communication with medical providers about sexual concerns. Findings indicated that sexual activities with partners were important; however, participants worried about their own physical limitations and reported frequent physical (e.g., bone pains) and vaginal pain associated with intercourse. When women raised concerns about these issues in clinical settings, medical providers often focused exclusively on vaginal lubricants, which did not address the entirety of women's problems or concerns. In addition, women diagnosed with metastatic breast cancer reported needing additional resources about specialized vaginal lubricants, nonpenetrative and nongenitally focused sex, and sexual positions that did not compromise their physical health yet still provided pleasure.