Effects of Self-Rated Health and Self-Rated Economic Situation on Depressed Mood Via Life Satisfaction Among Older Adults in Costa Rica

Objective: The study examined the relationship of self-rated health and self-rated economic situation with depressed mood, and life satisfaction as mediator of this relationship among older adults in Costa Rica. Method: A longitudinal study was conducted with a subsample (N = 1,618) from the Costa Rican Longevity and Healthy Aging Study (CRELES). Self-rated health, self-rated economic situation, depressed mood, and life satisfaction were measured at baseline, and depressed mood was reassessed 18 months later. Putative mechanisms for changes in depressed mood were examined by means of conditional process analysis. Results: Self-rated health was negatively associated to depressed mood. This effect took place via life satisfaction. An interaction showed that better economic situation compensated the effect of a low self-rated health on life satisfaction. Discussion: This study suggests that subjective variables such as self-rated health, economic situation, and life satisfaction should be considered when addressing the onset of depressed mood.Wellcome Trust/[072406/Z/03/Z]//Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Sociales::Centro Centroamericano de Población (CCP

Kinase/phosphatase overexpression reveals pathways regulating hippocampal neuron morphology

Kinases and phosphatases that regulate neurite number versus branching versus extension are weakly correlated.The kinase family that most strongly enhances neurite growth is a family of non-protein kinases; sugar kinases related to NADK.Pathway analysis revealed that genes in several cancer pathways were highly active in enhancing neurite growth

A Strong B-cell Response Is Part of the Immune Landscape in Human High-Grade Serous Ovarian Metastases

This work was funded by Cancer Research UK (A16354), Swiss Cancer League (BIL KLS2883-02-2012); the European Research Council (ERC322566); Barts and The London Charity (467/1307 to ML and BLT 297/2249 to 2 PRC); Bloodwise (Bennett Fellowship to MC; ref 12002); UNC University Cancer Research Fund and UNC Oncology Clinical Translational Research Training Program (5K12CA120780; to BV); National Cancer Institute (P50 CA058223; to JSS)

Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML

Occurrence of the BCR-ABL[superscript T315I] gatekeeper mutation is among the most pressing challenges in the therapy of chronic myeloid leukemia (CML). Several BCR-ABL inhibitors have multiple targets and pleiotropic effects that could be exploited for their synergistic potential. Testing combinations of such kinase inhibitors identified a strong synergy between danusertib and bosutinib that exclusively affected CML cells harboring BCR-ABL[superscript T315I]. To elucidate the underlying mechanisms, we applied a systems-level approach comprising phosphoproteomics, transcriptomics and chemical proteomics. Data integration revealed that both compounds targeted Mapk pathways downstream of BCR-ABL, resulting in impaired activity of c-Myc. Using pharmacological validation, we assessed that the relative contributions of danusertib and bosutinib could be mimicked individually by Mapk inhibitors and collectively by downregulation of c-Myc through Brd4 inhibition. Thus, integration of genome- and proteome-wide technologies enabled the elucidation of the mechanism by which a new drug synergy targets the dependency of BCR-ABL[superscript T315I] CML cells on c-Myc through nonobvious off targets

Human Epidermal Neural Crest Stem Cells (hEPI-NCSC)—Characterization and Directed Differentiation into Osteocytes and Melanocytes

Here we describe the isolation, characterisation and ex-vivo expansion of human epidermal neural crest stem cells (hEPI-NCSC) and we provide protocols for their directed differentiation into osteocytes and melanocytes. hEPI-NCSC are neural crest-derived multipotent stem cells that persist into adulthood in the bulge of hair follicles. Multipotency and self-renewal were determined by in vitro clonal analyses. hEPI-NCSC generate all major neural crest derivatives, including bone/cartilage cells, neurons, Schwann cells, myofibroblasts and melanocytes. Furthermore, hEPI-NCSC express additional neural crest stem cell markers and global stem cell genes. To variable degrees and in a donor-dependent manner, hEPI-NCSC express the six essential pluripotency genes C-MYC, KLF4, SOX2, LIN28, OCT-4/POU5F1 and NANOG. hEPI-NCSC can be expanded ex vivo into millions of stem cells that remain mulitpotent and continue to express stem cell genes. The novelty of hEPI-NCSC lies in the combination of their highly desirable traits. hEPI-NCSC are embryonic remnants in a postnatal location, the bulge of hair follicles. Therefore they are readily accessible in the hairy skin by minimal invasive procedure. hEPI-NCSC are multipotent somatic stem cells that can be isolated reproducibly and with high yield. By taking advantage of their migratory ability, hEPI-NCSC can be isolated as a highly pure population of stem cells. hEPI-NCSC can undergo robust ex vivo expansion and directed differentiation. As somatic stem cells, hEPI-NCSC are conducive to autologous transplantation, which avoids graft rejection. Together, these traits make hEPI-NCSC novel and attractive candidates for future cell-based therapies and regenerative medicine

Population policies, programmes and the environment

Human consumption is depleting the Earth's natural resources and impairing the capacity of life-supporting ecosystems. Humans have changed ecosystems more rapidly and extensively over the past 50 years than during any other period, primarily to meet increasing demands for food, fresh water, timber, fibre and fuel. Such consumption, together with world population increasing from 2.6 billion in 1950 to 6.8 billion in 2009, are major contributors to environmental damage. Strengthening family-planning services is crucial to slowing population growth, now 78 million annually, and limiting population size to 9.2 billion by 2050. Otherwise, birth rates could remain unchanged, and world population would grow to 11 billion. Of particular concern are the 80 million annual pregnancies (38% of all pregnancies) that are unintended. More than 200 million women in developing countries prefer to delay their pregnancy, or stop bearing children altogether, but rely on traditional, less-effective methods of contraception or use no method because they lack access or face other barriers to using contraception. Family-planning programmes have a successful track record of reducing unintended pregnancies, thereby slowing population growth. An estimated $15 billion per year is needed for family-planning programmes in developing countries and donors should provide at least$5 billion of the total, however, current donor assistance is less than a quarter of this funding target