Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression

Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1. These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration

Gravitational Microlensing Evidence for a Planet Orbiting a Binary Star System

The study of extra-solar planetary systems has emerged as a new discipline of observational astronomy in the past few years with the discovery of a number of extra-solar planets. The properties of most of these extra-solar planets were not anticipated by theoretical work on the formation of planetary systems. Here we report observations and light curve modeling of gravitational microlensing event MACHO-97-BLG-41, which indicates that the lens system consists of a planet orbiting a binary star system. According to this model, the mass ratio of the binary star system is 3.8:1 and the stars are most likely to be a late K dwarf and an M dwarf with a separation of about 1.8 AU. A planet of about 3 Jupiter masses orbits this system at a distance of about 7 AU. If our interpretation of this light curve is correct, it represents the first discovery of a planet orbiting a binary star system and the first detection of a Jovian planet via the gravitational microlensing technique. It suggests that giant planets may be common in short period binary star systems.Comment: 11 pages, with 1 color and 2 b/w Figures included (published version

Increased Rate of CD4+ T-Cell Decline and Faster Time to Antiretroviral Therapy in HIV-1 Subtype CRF01_AE Infected Seroconverters in Singapore

It remains controversial as to whether HIV-1 subtypes influence disease progression. Singapore offers a unique opportunity to address this issue due to the presence of co-circulating subtypes. We compared subtype CRF01_AE and non-CRF01_AE infected patients, with regards to estimated annual rate of CD4+ T-cell loss and time from estimated data of seroconversion (EDS) to antiretroviral therapy (ART).We recruited ART-naive patients with known dates of seroconversion between October 2002 and December 2007 at the Singapore Communicable Disease Centre, the national reference treatment centre. Multilevel mixed-effects models were used to analyse the rate of CD4+ T-cell decline. Time from EDS to ART was analyzed with the Kaplan-Meier survival method and compared with Cox proportional hazards models. viral load.Infecting subtype significantly impacted the rate of CD4+ T-cell loss and time to treatment in this cohort. Studies to understand the biological basis for this difference could further our understanding of HIV pathogenesis