The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease.

J Biol Chem. 2005 Dec 30;280(52):43243-56. Epub 2005 Oct 5. The absence of ABCA1 decreases soluble ApoE levels but does not diminish amyloid deposition in two murine models of Alzheimer disease. Hirsch-Reinshagen V, Maia LF, Burgess BL, Blain JF, Naus KE, McIsaac SA, Parkinson PF, Chan JY, Tansley GH, Hayden MR, Poirier J, Van Nostrand W, Wellington CL. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V4Z 5H5, Canada. Abstract ABCA1, a cholesterol transporter expressed in the brain, has been shown recently to be required to maintain normal apoE levels and lipidation in the central nervous system. In addition, ABCA1 has been reported to modulate beta-amyloid (Abeta) production in vitro. These observations raise the possibility that ABCA1 may play a role in the pathogenesis of Alzheimer disease. Here we report that the deficiency of ABCA1 does not affect soluble or guanidine-extractable Abeta levels in Tg-SwDI/B or amyloid precursor protein/presenilin 1 (APP/PS1) mice, but rather is associated with a dramatic reduction in soluble apoE levels in brain. Although this reduction in apoE was expected to reduce the amyloid burden in vivo, we observed that the parenchymal and vascular amyloid load was increased in Tg-SwDI/B animals and was not diminished in APP/PS1 mice. Furthermore, we observed an increase in the proportion of apoE retained in the insoluble fraction, particularly in the APP/PS1 model. These data suggested that ABCA1-mediated effects on apoE levels and lipidation influenced amyloidogenesis in vivo. PMID: 16207707 [PubMed - indexed for MEDLINE

Equation of state for Universe from similarity symmetries

In this paper we proposed to use the group of analysis of symmetries of the dynamical system to describe the evolution of the Universe. This methods is used in searching for the unknown equation of state. It is shown that group of symmetries enforce the form of the equation of state for noninteracting scaling multifluids. We showed that symmetries give rise the equation of state in the form $p=-\Lambda+w_{1}\rho(a)+w_{2}a^{\beta}+0$ and energy density $\rho=\Lambda+\rho_{01}a^{-3(1+w)}+\rho_{02}a^{\beta}+\rho_{03}a^{-3}$, which is commonly used in cosmology. The FRW model filled with scaling fluid (called homological) is confronted with the observations of distant type Ia supernovae. We found the class of model parameters admissible by the statistical analysis of SNIa data. We showed that the model with scaling fluid fits well to supernovae data. We found that $\Omega_{\text{m},0} \simeq 0.4$ and $n \simeq -1$ ($\beta = -3n$), which can correspond to (hyper) phantom fluid, and to a high density universe. However if we assume prior that $\Omega_{\text{m},0}=0.3$ then the favoured model is close to concordance $\Lambda$CDM model. Our results predict that in the considered model with scaling fluids distant type Ia supernovae should be brighter than in $\Lambda$CDM model, while intermediate distant SNIa should be fainter than in $\Lambda$CDM model. We also investigate whether the model with scaling fluid is actually preferred by data over $\Lambda$CDM model. As a result we find from the Akaike model selection criterion prefers the model with noninteracting scaling fluid.Comment: accepted for publication versio

The induction of behavioural sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens

Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi–Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73532/1/j.1460-9568.2004.03612.x.pd

Model-independent dark energy test with sigma_8 using results from the Wilkinson Microwave Anisotropy Probe

By combining the recent WMAP measurements of the cosmic microwave background anisotropies and the results of the recent luminosity distance measurements to type-Ia supernovae, we find that the normalization of the matter power spectrum on cluster scales, sigma_8, can be used to discriminate between dynamical models of dark energy (quintessence models) and a conventional cosmological constant model (LCDM).Comment: 5 pages, 6 figures. Additional discussion and reference, matches PRD accepted versio

The SPTPoL extended cluster survey

We describe the observations and resultant galaxy cluster catalog from the 2770 deg2 SPTpol Extended Cluster Survey (SPT-ECS). Clusters are identified via the Sunyaev-Zel'dovich (SZ) effect and confirmed with a combination of archival and targeted follow-up data, making particular use of data from the Dark Energy Survey (DES). With incomplete follow-up we have confirmed as clusters 244 of 266 candidates at a detection significance ξ ≥ 5 and an additional 204 systems at 4 4 threshold, and 10% of their measured SZ flux. We associate SZ-selected clusters, from both SPT-ECS and the SPT-SZ survey, with clusters from the DES redMaPPer sample, and we find an offset distribution between the SZ center and central galaxy in general agreement with previous work, though with a larger fraction of clusters with significant offsets. Adopting a fixed Planck-like cosmology, we measure the optical richness-SZ mass (l - M) relation and find it to be 28% shallower than that from a weak-lensing analysis of the DES data-a difference significant at the 4σ level-with the relations intersecting at λ = 60. The SPT-ECS cluster sample will be particularly useful for studying the evolution of massive clusters and, in combination with DES lensing observations and the SPT-SZ cluster sample, will be an important component of future cosmological analyses

Study of the lineshape of the chi(c1) (3872) state

A study of the lineshape of the chi(c1) (3872) state is made using a data sample corresponding to an integrated luminosity of 3 fb(-1) collected in pp collisions at center-of-mass energies of 7 and 8 TeV with the LHCb detector. Candidate chi(c1)(3872) and psi(2S) mesons from b-hadron decays are selected in the J/psi pi(+)pi(-) decay mode. Describing the lineshape with a Breit-Wigner function, the mass splitting between the chi(c1 )(3872) and psi(2S) states, Delta m, and the width of the chi(c1 )(3872) state, Gamma(Bw), are determined to be (Delta m=185.598 +/- 0.067 +/- 0.068 Mev,)(Gamma BW=1.39 +/- 0.24 +/- 0.10 Mev,) where the first uncertainty is statistical and the second systematic. Using a Flatte-inspired model, the mode and full width at half maximum of the lineshape are determined to be (mode=3871.69+0.00+0.05 MeV.)(FWHM=0.22-0.04+0.13+0.07+0.11-0.06-0.13 MeV, ) An investigation of the analytic structure of the Flatte amplitude reveals a pole structure, which is compatible with a quasibound D-0(D) over bar*(0) state but a quasivirtual state is still allowed at the level of 2 standard deviations

Measurement of the CKM angle γγ in B±→DK±B^\pm\to D K^\pm and B±→Dπ±B^\pm \to D π^\pm decays with D→KS0h+h−D \to K_\mathrm S^0 h^+ h^-

A measurement of $CP$-violating observables is performed using the decays $B^\pm\to D K^\pm$ and $B^\pm\to D \pi^\pm$, where the $D$ meson is reconstructed in one of the self-conjugate three-body final states $K_{\mathrm S}\pi^+\pi^-$ and $K_{\mathrm S}K^+K^-$ (commonly denoted $K_{\mathrm S} h^+h^-$). The decays are analysed in bins of the $D$-decay phase space, leading to a measurement that is independent of the modelling of the $D$-decay amplitude. The observables are interpreted in terms of the CKM angle $\gamma$. Using a data sample corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$ collected in proton-proton collisions at centre-of-mass energies of $7$, $8$, and $13\,\text{TeV}$ with the LHCb experiment, $\gamma$ is measured to be $\left(68.7^{+5.2}_{-5.1}\right)^\circ$. The hadronic parameters $r_B^{DK}$, $r_B^{D\pi}$, $\delta_B^{DK}$, and $\delta_B^{D\pi}$, which are the ratios and strong-phase differences of the suppressed and favoured $B^\pm$ decays, are also reported

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease