ApoA-I Deficiency Increases Cortical Amyloid Deposition, Cerebral Amyloid Angiopathy, Cortical and Hippocampal Astrogliosis, and Amyloid-associated Astrocyte Reactivity in APP/PS1 Mice

Background Alzheimer’s disease (AD) is defined by amyloid beta (Aβ) plaques and neurofibrillary tangles and characterized by neurodegeneration and memory loss. The majority of AD patients also have Aβ deposition in cerebral vessels known as cerebral amyloid angiopathy (CAA), microhemorrhages, and vascular co-morbidities, suggesting that cerebrovascular dysfunction contributes to AD etiology. Promoting cerebrovascular resilience may therefore be a promising therapeutic or preventative strategy for AD. Plasma high-density lipoproteins (HDL) have several vasoprotective functions and are associated with reduced AD risk in some epidemiological studies and with reduced Aβ deposition and Aβ-induced inflammation in 3D engineered human cerebral vessels. In mice, deficiency of apoA-I, the primary protein component of HDL, increases CAA and cognitive dysfunction, whereas overexpression of apoA-I from its native promoter in liver and intestine has the opposite effect and lessens neuroinflammation. Similarly, acute peripheral administration of HDL reduces soluble Aβ pools in the brain and some studies have observed reduced CAA as well. Here, we expand upon the known effects of plasma HDL in mouse models and in vitro 3D artery models to investigate the interaction of amyloid, astrocytes, and HDL on the cerebrovasculature in APP/PS1 mice. Methods APP/PS1 mice deficient or hemizygous for Apoa1 were aged to 12 months. Plasma lipids, amyloid plaque deposition, Aβ protein levels, protein and mRNA markers of neuroinflammation, and astrogliosis were assessed using ELISA, qRT-PCR, and immunofluorescence. Contextual and cued fear conditioning were used to assess behavior. Results In APP/PS1 mice, complete apoA-I deficiency increased total and vascular Aβ deposition in the cortex but not the hippocampus compared to APP/PS1 littermate controls hemizygous for apoA-I. Markers of both general and vascular neuroinflammation, including Il1b mRNA, ICAM-1 protein, PDGFRβ protein, and GFAP protein, were elevated in apoA-I-deficient APP/PS1 mice. Additionally, apoA-I-deficient APP/PS1 mice had elevated levels of vascular-associated ICAM-1 in the cortex and hippocampus and vascular-associated GFAP in the cortex. A striking observation was that astrocytes associated with cerebral vessels laden with Aβ or associated with Aβ plaques showed increased reactivity in APP/PS1 mice lacking apoA-I. No behavioral changes were observed. Conclusions ApoA-I-containing HDL can reduce amyloid pathology and astrocyte reactivity to parenchymal and vascular amyloid in APP/PS1 mice

Beta-delayed proton emission from 20Mg

Beta-delayed proton emission from 20 Mg has been measured at ISOLDE, CERN, with the ISOLDE Decay Station (IDS) setup including both charged-particle and gamma-ray detection capabilities. A total of 27 delayed proton branches were measured including seven so far unobserved. An updated decay scheme, including three new resonances above the proton separation energy in 20 Na and more precise resonance energies, is presented. Beta-decay feeding to two resonances above the Isobaric Analogue State (IAS) in 20 Na is observed. This may allow studies of the 4032.9(2.4)keV resonance in 19 Ne through the beta decay of 20 Mg, which is important for the astrophysically relevant reaction 15O( $\alpha$ , $\gamma$ )19Ne . Beta-delayed protons were used to obtain a more precise value for the half-life of 20 Mg, 91.4(1.0)ms

Decay studies of the long-lived states in Tl-186

Decay spectroscopy of the long-lived states in Tl-186 has been performed at the ISOLDE Decay Station at ISOLDE, CERN. The a decay from the low-spin (2(-)) state in Tl-186 was observed for the first time and a half-life of 3.4(-0.)(4)(+0.5) s was determined. Based on the alpha-decay energy, the relative positions of the long-lived states were fixed, with the (2(-)) state as the ground state, the 7((+)) state at 77(56) keV, and the 10((-)) state at 451(56) keV. The level scheme of the internal decay of the Tl-186(10((-))) state [T-1/2 = 3.40(9) s], which was known to decay solely through emission of 374-keV gamma-ray transition, was extended and a lower limit for the beta-decay branching b(beta) > 5.9(3)% was determined. The extracted retardation factors for the gamma decay of the 10((-) )state were compared to the available data in neighboring odd-odd thallium isotopes indicating the importance of the pi d(3/2) shell in the isomeric decay and significant structure differences between Tl-184 and Tl-186.Peer reviewe

Fast-timing study of the l -forbidden 12+→32+ M1 transition in Sn 129 FAST-TIMING STUDY of the l -FORBIDDEN ⋯ R. LICǎ et al.

© 2016 authors. Published by the American Physical Society.The levels in Sn129 populated from the β- decay of In129 isomers were investigated at the ISOLDE facility of CERN using the newly commissioned ISOLDE Decay Station (IDS). The lowest 12+ state and the 32+ ground state in Sn129 are expected to have configurations dominated by the neutron s12 (l=0) and d32 (l=2) single-particle states, respectively. Consequently, these states should be connected by a somewhat slow l-forbidden M1 transition. Using fast-timing spectroscopy we have measured the half-life of the 12+ 315.3-keV state, T12= 19(10) ps, which corresponds to a moderately fast M1 transition. Shell-model calculations using the CD-Bonn effective interaction, with standard effective charges and g factors, predict a 4-ns half-life for this level. We can reconcile the shell-model calculations to the measured T12 value by the renormalization of the M1 effective operator for neutron holes

Competition between Allowed and First-Forbidden beta Decay : The Case of Hg-208 -> Tl-2(0)8

The beta decay of Hg-208 into the one-proton hole, one neutron-particle Tl-208(81)127 nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N > 126, Z 0(-)beta decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.Peer reviewe

Life course trajectories of alcohol consumption in the United Kingdom using longitudinal data from nine cohort studies.

Background Alcohol consumption patterns change across life and this is not fully captured in cross-sectional series data. Analysis of longitudinal data, with repeat alcohol measures, is necessary to reveal changes within the same individuals as they age. Such data are scarce and few studies are able to capture multiple decades of the life course. Therefore, we examined alcohol consumption trajectories, reporting both average weekly volume and frequency, using data from cohorts with repeated measures that cover different and overlapping periods of life. Methods Data were from nine UK-based prospective cohorts with at least three repeated alcohol consumption measures on individuals (combined sample size of 59,397 with 174,666 alcohol observations), with data spanning from adolescence to very old age (90 years plus). Information on volume and frequency of drinking were harmonised across the cohorts. Predicted volume of alcohol by age was estimated using random effect multilevel models fitted to each cohort. Quadratic and cubic polynomial terms were used to describe non-linear age trajectories. Changes in drinking frequency by age were calculated from observed data within each cohort and then smoothed using locally weighted scatterplot smoothing. Models were fitted for men and women separately. Results We found that, for men, mean consumption rose sharply during adolescence, peaked at around 25 years at 20 units per week, and then declined and plateaued during mid-life, before declining from around 60 years. A similar trajectory was seen for women, but with lower overall consumption (peak of around 7 to 8 units per week). Frequent drinking (daily or most days of the week) became more common during mid to older age, most notably among men, reaching above 50% of men. Conclusions This is the first attempt to synthesise longitudinal data on alcohol consumption from several overlapping cohorts to represent the entire life course and illustrates the importance of recognising that this behaviour is dynamic. The aetiological findings from epidemiological studies using just one exposure measure of alcohol, as is typically done, should be treated with caution. Having a better understanding of how drinking changes with age may help design intervention strategies

First beta-decay spectroscopy of In-135 and new beta-decay branches of In-134

The beta decay of the neutron-rich In-134 and In-135 was investigated experimentally in order to provide new insights into the nuclear structure of the tin isotopes with magic proton number Z = 50 above the N = 82 shell. The beta-delayed gamma-ray spectroscopy measurement was performed at the ISOLDE facility at CERN, where indium isotopes were selectively laser-ionized and on-line mass separated. Three beta-decay branches of In-134 were established, two of which were observed for the first time. Population of neutron-unbound states decaying via. rays was identified in the two daughter nuclei of In-134, Sn-134 and Sn-133, at excitation energies exceeding the neutron separation energy by 1 MeV. The beta-delayed one- and two-neutron emission branching ratios of In-134 were determined and compared with theoretical calculations. The beta-delayed one-neutron decay was observed to be dominant beta-decay branch of In-134 even though the Gamow-Teller resonance is located substantially above the two-neutron separation energy of Sn-134. Transitions following the beta decay of In-135 are reported for the first time, including. rays tentatively attributed to Sn-135. In total, six new levels were identified in Sn-134 on the basis of the beta.. coincidences observed in the In-134 and In-135 beta decays. A transition that might be a candidate for deexciting the missing neutron single-particle 13/2(+) state in Sn-133 was observed in both beta decays and its assignment is discussed. Experimental level schemes of Sn-134 and Sn-135 are compared with shell-model predictions. Using the fast timing technique, half-lives of the 2(+), 4(+), and 6(+) levels in Sn-134 were determined. From the lifetime of the 4(+) state measured for the first time, an unexpectedly large B(E2; 4(+)-> 2(+)) transition strength was deduced, which is not reproduced by the shell-model calculations.Peer reviewe

Study of exotic decay of Cs isotope close to the proton drip line

The neutron-deficient 115Cs was produced at ISOLDE, CERN by spallation reaction using 1.4 GeV proton on LaC2 target. The exotic decay modes were studied by using a charged particle array (DSSD and pad detectors) and a γ-detector array (four Clovers) at the ISOLDE decay station (IDS). In this report, results on observed β-delayed particle emission from 115Cs, a nucleus close to proton drip line, is presented. By measuring the time distribution in the delayed proton spectrum, the half-life of the ground state of 115Cs was extracted. The obtained half-life is in agreement with previous reported value. For the first time, the p-unbound states of 115Xe, obtained by measuring beta-delayed protons from 115Cs is reported

Simultaneous γ-ray and electron spectroscopy of 182,184,186Hg isotopes

Background: The mercury isotopes around N=104 are a well-known example of nuclei exhibiting shape coexistence. Mixing of configurations can be studied by measuring the monopole strength ρ2(E0), however, currently the experimental information is scarce and lacks precision, especially for the Iπ→Iπ (I≠0) transitions. Purpose: The goals of this study were to increase the precision of the known branching ratios and internal conversion coefficients, to increase the amount of available information regarding excited states in Hg182,184,186, and to interpret the results in the framework of shape coexistence using different models. Method: The low-energy structures in Hg182,184,186 were populated in the β decay of Tl182,184,186, produced at ISOLDE, CERN and purified by laser ionization and mass separation. The γ-ray and internal conversion electron events were detected by five germanium clover detectors and a segmented silicon detector, respectively, and correlated in time to build decay schemes. Results: In total, 193, 178, and 156 transitions, including 144, 140, and 108 observed for the first time in a β-decay experiment, were assigned to Hg182,184,186, respectively. Internal conversion coefficients were determined for 23 transitions, out of which 12 had an E0 component. Extracted branching ratios allowed the sign of the interference term in Hg182 as well as ρ2(E0;02+→01+) and B(E2;02+→21+) in Hg184 to be determined. By means of electron-electron coincidences, the 03+ state was identified in Hg184. The experimental results were qualitatively reproduced by five theoretical approaches, the interacting boson model with configuration mixing with two different parametrizations, the general Bohr Hamiltonian, the beyond mean-field model, and the symmetry-conserving configuration-mixing model. However, a quantitative description is lacking. Conclusions: The presence of shape coexistence in neutron-deficient mercury isotopes was confirmed and evidence for the phenomenon existing at higher energies was found. The new experimental results provide important spectroscopic input for future Coulomb excitation studies

Competition between allowed and first-forbidden β decays of at 208 and expansion of the Po 208 level scheme

The structure of Po208 populated through the EC/β+ decay of At208 is investigated using γ-ray spectroscopy at the ISOLDE Decay Station. The presented level scheme contains 27 new excited states and 43 new transitions, as well as a further 50 previously observed γ rays which have been (re)assigned a position. The level scheme is compared to shell model calculations. Through this analysis approximately half of the β-decay strength of At208 is found to proceed via allowed decay and half via first-forbidden decay. The first-forbidden transitions predominantly populate core excited states at high excitation energies, which is qualitatively understood using shell model considerations. This mass region provides an excellent testing ground for the competition between allowed and first-forbidden β-decay calculations, important for the detailed understanding of the nucleosynthesis of heavy elements