Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors

Objective To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated

Metabolic Syndrome and Onset of Depressive Symptoms in the Elderly: Findings from the Three-City Study

OBJECTIVE-Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and the onset of depressive symptoms according to different age-groups in a large, general elderly population.RESEARCH DESIGN AND METHODS-This was a prospective cohort study of 4,446 men and women aged 65-91 years who were free of depression or depressive symptoms at baseline (the Three-City Study, France). MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale score >= 16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups.RESULTS-After adjusting for a large range of potential confounders, we observed MetS to be associated with 1.73-fold (95% CI 1.02-2.95) odds for new-onset depressive symptoms in the youngest age-group (65-70 years at baseline), independently of cardiovascular diseases. No such association was seen in older age-groups.CONCLUSIONS-Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged people can be extended to older adults but not to the oldest ones. Additional research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65-70 years. Diabetes Care 34:904-909, 201

Search for new resonant states in 10C and 11C and their impact on the cosmological lithium problem

The observed primordial 7Li abundance in metal-poor halo stars is found to be lower than its Big-Bang nucleosynthesis (BBN) calculated value by a factor of approximately three. Some recent works suggested the possibility that this discrepancy originates from missing resonant reactions which would destroy the 7Be, parent of 7Li. The most promising candidate resonances which were found include a possibly missed 1- or 2- narrow state around 15 MeV in the compound nucleus 10C formed by 7Be+3He and a state close to 7.8 MeV in the compound nucleus 11C formed by 7Be+4He. In this work, we studied the high excitation energy region of 10C and the low excitation energy region in 11C via the reactions 10B(3He,t)10C and 11B(3He,t)11C, respectively, at the incident energy of 35 MeV. Our results for 10C do not support 7Be+3He as a possible solution for the 7Li problem. Concerning 11C results, the data show no new resonances in the excitation energy region of interest and this excludes 7Be+4He reaction channel as an explanation for the 7Li deficit.Comment: Accepted for publication in Phys. Rev. C (Rapid Communication

Reprogramming Primordial Germ Cells into Pluripotent Stem Cells

Background: Specification of primordial germ cells (PGCs) results in the conversion of pluripotent epiblast cells into monopotent germ cell lineage. Blimp1/Prmt5 complex plays a critical role in the specification and maintenance of the early germ cell lineage. However, PGCs can be induced to dedifferentiate back to a pluripotent state as embryonic germ (EG) cells when exposed to exogenous signaling molecules, FGF-2, LIF and SCF. Methodology and Principal Findings: Here we show that Trichostatin A (TSA), an inhibitor of histone deacetylases, is a highly potent agent that can replace FGF-2 to induce dedifferentiation of PGCs into EG cells. A key early event during dedifferentiation of PGCs in response to FGF-2 or TSA is the down-regulation of Blimp1, which reverses and apparently relieves the cell fate restriction imposed by it. Notably, the targets of Blimp1, which include c-Myc and Klf-4, which represent two of the key factors known to promote reprogramming of somatic cells to pluripotent state, are up-regulated. We also found early activation of the LIF/Stat-3 signaling pathway with the translocation of Stat-3 into the nucleus. By contrast, while Prmt5 is retained in EG cells, it translocates from the nucleus to the cytoplasm where it probably has an independent role in regulating pluripotency. Conclusions/Significance: We propose that dedifferentiation of PGCs into EG cells may provide significant mechanistic insights on early events associated with reprogramming of committed cells to a pluripotent state

Dynamic Distribution of Histone H4 Arginine 3 Methylation Marks in the Developing Murine Cortex

Epigenetic modifications regulate key transitions in cell fate during development of the central nervous system (CNS). During cortical development the initial population of proliferative neuroepithelial precursor cells give rise to neurons and then glia in a strict temporal order. Neurogenesis and gliogenesis are accompanied by a switch from symmetric to asymmetric divisions of the neural precursor cells generating another precursor and a differentiated progeny. To investigate whether specific post-translational histone modifications define specific stages of neural precursor differentiation during cortical development I focussed on the appearance of two different types of histone arginine methylation, the dimethyl symmetric H4R3 (H4R3me2s) and dimethyl asymmetric H4R3 (H4R3me2a) in the developing mouse cortex.An immunohistochemical study of the developing cortex at different developmental stages was performed to detect the distribution of H4R3me2s and H4R3me2a modifications. I analysed the distribution of these modifications in: 1) undifferentiated neural precursors, 2) post-mitotic neurons and 3) developing oligodendrocyte precursors (OLPs) using lineage-specific and histone modification-specific antibodies to co-label the cells. I found that the proliferative neuroepithelium during the stage of mainly symmetric expansive divisions is characterised by the prevalence of H4R3me2s modification and almost no detectable H4R3me2a modification. However, at a later stage, when the cortical layers with post-mitotic neurons have begun forming, both H4R3me2a and H4R3me2s modifications are detected in the post-mitotic neurons and in the developing OLPs.I propose that the H4R3me2s modification forms part of the "histone code" of undifferentiated neural precursors. The later appearance of the H4R3me2a modifications specifies the onset of neurogenesis and gliogenesis and the commitment of the NSCs to differentiate. Thus, the sequential appearance of the two different H4R3 methylation marks may define a particular cellular state of the NSCs during their development and differentiation demonstrating the role of histone arginine methylation in cortical development

Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BackgroundCigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.Methods and findingsA total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (ConclusionsThe probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause

Search for resonant states in 10C and 11C and their impact on the primordial 7Li abundance

The cosmological 7Li problem arises from the significant discrepancy of about a factor 3 between the predicted primordial 7Li abundance and the observed one. The main process for the production of 7Li during Big-Bang nucleosynthesis is the decay of 7Be. Many key nuclear reactions involved in the production and destruction of 7Be were investigated in attempt to explain the 7Li deficit but none of them led to successful conclusions. However, some authors suggested recently the possibility that the destruction of 7Be by 3He and 4He may reconcile the predictions and observations if missing resonant states in the compound nuclei 10C and 11C exist. Hence, a search of these missing resonant states in 10C and 11C was investigated at the Orsay Tandem-Alto facility through 10B(3He,t)10C and 11B(3He,t)11C charge-exchange reactions respectively. After a short overview of the cosmological 7Li problem from a nuclear physics point of view, a description of the Orsay experiment will be given as well as the obtained results and their impact on the 7Li problem

Study of the 26Al(n,p)26Mg and 26Al(n,α)23Na reactions using the 27Al(p,p')27Al inelastic scattering reaction

26Al was the first cosmic radioactivity ever detected in the galaxy as well as one of the first extinct radioactivity observed in refractory phases of meteorites. Its nucleosynthesis in massive stars is still uncertain mainly due to the lack of nuclear information concerning the 26Al(n,p)26Mg and 26 Al(n,α)23Na reactions. We report on a single and coincidence measurement of the 27Al(p,p')27Al(p)26Mg and 27Al(p,p')27Al(α)23Na reactions performed at the Orsay TANDEM facility aiming at the spectroscopy study of 27Al above the neutron threshold. Fourteen states are observed for the first time within 350 keV above the 26Al+n threshold