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

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

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

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

The Individual Blood Cell Telomere Attrition Rate Is Telomere Length Dependent

Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at ∼10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = –0.164, P<0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = –0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = –0.691, P<0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

Background: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E e4 allele (APOE*4) carrier status were associated with decline. Methods and findings: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42, 170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval CI] -0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI -0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI -0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI -0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI 0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI 0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI -0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI -0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. Conclusions: Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data

Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study

<p>Abstract</p> <p>Background</p> <p>Previous studies have found associations between the use of central nervous system medication and the risk of cognitive decline in the aged. Our aim was to assess whether the use of a single central nervous system (CNS) medication and, on the other hand, the combined use of multiple CNS medications over time are related to the risk of cognitive decline in an older (≥ 65 yrs) population that is cognitively intact at baseline.</p> <p>Methods</p> <p>We conducted a longitudinal population-based study of cognitively intact older adults. The participants were 65 years old or older and had Mini-Mental State Examination (MMSE) sum scores of 24 points or higher. The study included a 7.6-year follow-up. The use of benzodiazepines and related drugs (BZDs), antipsychotics (APs), antidepressants (ADs), opioids (Ops), anticholinergics (AChs) and antiepileptics (AEs) was determined at baseline and after a 7.6-years of the follow-up period. Cognitive functioning was used as an outcome variable measured with MMSE at baseline and at the mean follow-up of 7.6 years. Control variables were adjusted with analyses of covariance.</p> <p>Results</p> <p>After adjusting for control variables, the use of Ops and the concomitant use of Ops and BZDs as well as the use of Ops and any CNS medication were associated with cognitive decline. The use of AChs was associated with decline in cognitive functioning only in men.</p> <p>Conclusions</p> <p>Of all the CNS medications analyzed in this study, the use of Ops may have the greatest effect on cognitive functioning in the ageing population. Due to small sample sizes these findings cannot be generalized to the unselected ageing population. More studies are needed concerning the long-term use of CNS medications, especially their concomitant use, and their potential cognitive effects.</p

Hormone Treatment, Estrogen Receptor Polymorphisms and Mortality: A Prospective Cohort Study

International audienceBACKGROUND: The association between hormone treatment (HT) and mortality remains controversial. This study aimed to determine whether the risk of mortality associated with HT use varies depending on the specific characteristics of treatment and genetic variability in terms of the estrogen receptor. METHODOLOGY/PRINCIPAL FINDINGS: A prospective, population-based study of 5135 women aged 65 years and older who were recruited from three cities in France and followed over six years. Detailed information related to HT use was obtained and five estrogen receptor polymorphisms were genotyped. The total follow-up was 25,436 person-years and during this time 352 women died. Cancer (36.4%) and cardiovascular disease (19.3%) were the major causes of death. Cox proportional hazards models adjusted for age, education, centre, living situation, comorbidity, depression, physical and mental incapacities, indicated no significant association between HT and mortality, regardless of the type or duration of treatment, or the age at initiation. However, the association between HT and all-cause or cancer-related mortality varied across women, with significant interactions identified with three estrogen receptor polymorphisms (p-values = 0.004 to 0.03) in adjusted analyses. Women carrying the C allele of ESR1 rs2234693 had a decreased risk of all-cause mortality with HT (HR: 0.42, 95% CI: 0.18-0.97), while in stark contrast, those homozygous for the T allele had a significantly increased risk of cancer-related mortality (HR: 3.18, 95% CI: 1.23-8.20). The findings were similar for ESR1 rs9340799 and ESR2 rs1271572. CONCLUSIONS/SIGNIFICANCE: The risk of mortality was not associated with HT duration, type or age at initiation. It was however not equal across all women, with some women appearing genetically more vulnerable to the effects of HT in terms of their estrogen receptor genotype. These findings, if confirmed in another independent study, may help explain the differential susceptibility of women to the beneficial or adverse effects of HT

Plasmodium falciparum Choline Kinase Inhibition Leads to a Major Decrease in Phosphatidylethanolamine Causing Parasite Death

This work was supported by Agencia Aragonesa para la Investigación y Desarrollo (ARAID), Ministerio de Economía y Competitividad (CTQ2013-44367-C2-2-P to R.H.-G.) and Diputación General de Aragón (DGA; B89 to R.H.-G.) and the EU Seventh Framework Programme (2007–2013) under BioStruct-X (grant agreement 283570 and BIOSTRUCTX 5186, to R.H.-G.). T.K.S. was supported by the Wellcome Trust grant 093228 and European Community’s Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED).Malaria is a life-threatening disease caused by different species of the protozoan parasite Plasmodium, with P. falciparum being the deadliest. Increasing parasitic resistance to existing antimalarials makes the necessity of novel avenues to treat this disease an urgent priority. The enzymes responsible for the synthesis of phosphatidylcholine and phosphatidylethanolamine are attractive drug targets to treat malaria as their selective inhibition leads to an arrest of the parasite’s growth and cures malaria in a mouse model. We present here a detailed study that reveals a mode of action for two P. falciparum choline kinase inhibitors both in vitro and in vivo. The compounds present distinct binding modes to the choline/ethanolamine-binding site of P. falciparum choline kinase, reflecting different types of inhibition. Strikingly, these compounds primarily inhibit the ethanolamine kinase activity of the P. falciparum choline kinase, leading to a severe decrease in the phosphatidylethanolamine levels within P. falciparum, which explains the resulting growth phenotype and the parasites death. These studies provide an understanding of the mode of action, and act as a springboard for continued antimalarial development efforts selectively targeting P. falciparum choline kinase.Publisher PDFPeer reviewe

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study

Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54–105 (mean = 72.7) years and without dementia at baseline. Studies had 2–15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = −0.1, SE = 0.01), APOE*4 carriage (B = −0.31, SE = 0.11), depression (B = −0.11, SE = 0.06), diabetes (B = −0.23, SE = 0.10), current smoking (B = −0.20, SE = 0.08), and history of stroke (B = −0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = −0.07, SE = 0.01), APOE*4 carriage (B = −0.41, SE = 0.18), and diabetes (B = −0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = −0.24, SE = 0.12), and between diabetes and cognitive decline (B = −0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences