•Somatic mosaicism (SM) of the Y chr. occurs more frequently in blood than brain.•SM of the Y and female X chr. are associated with aggregate gene expression.•SM of the Y and female X chr. is ...associated with Alzheimer’s neuropathology.
In the blood, mosaic somatic aneuploidy (mSA) of all chromosomes has been found to be associated with adverse health outcomes, including hematological cancer. Sex chromosome mSA in the blood has been found to occur at a higher rate than autosomal mSA. Mosaic loss of the Y chromosome is the most common copy number alteration in males, and has been found to be associated with Alzheimer’s disease (AD) in blood lymphocytes. mSA of the sex chromosomes has also been identified in the brain; however, little is known about its frequency across individuals. Using WGS data from 362 males and 719 females from the ROSMAP cohort, we quantified the relative rate of sex chromosome mSA in the dorsolateral prefrontal cortex (DLPFC), cerebellum and whole blood. To ascertain the functionality of observed sex chromosome mosaicism in the DLPFC, we examined its correlation with chromosome X and Y gene expression as well as neuropathological and clinical characteristics of AD and cognitive ageing. In males, we found that mSA of the Y chromosome occurs more frequently in blood than in the DLPFC or cerebellum. In the DLPFC, the presence of at least one APOE4 allele was associated with a reduction in read depth of the Y chromosome (p = 1.9e−02). In the female DLPFC, a reduction in chromosome X read depth was associated with reduced cognition at the last clinical visit and faster rate of cognitive decline (p = 7.8e−03; p = 1.9e−02). mSA of all sex chromosomes in the DLPFC were associated with aggregate measures of gene expression, implying functional impact. Our results provide insight into the relative rate of mSA between tissues and suggest that Y and female X chromosome read depth in the DLPFC is modestly associated with late AD risk factors and cognitive pathologies.
We report measurements of the branching fraction and \(\it CP\) asymmetry in \(B^{0} \to \pi^{0} \pi^{0}\) decays reconstructed at Belle II in an electron-positron collision sample containing \(198 ...\times 10^{6}\) \(B\overline{B}\) pairs. We measure a branching fraction \(\mathcal{B}(\Bpipi) = (1.38 \pm 0.27 \pm 0.22) \times 10^{-6}\) and a \(\it CP\) asymmetry \(\Acp(\Bpipi) = 0.14 \pm 0.46 \pm 0.07\), where the first uncertainty is statistical and the second is systematic.
We report a search for lepton-flavor-violating decays \(\tau^- \to \ell^- \phi\) (\(\ell^- =e^-,\mu^-\)) at the Belle II experiment, using a sample of electron-positron data produced at the SuperKEKB ...collider in 2019-2021 and corresponding to an integrated luminosity of 190 fb\(^{-1}\). We use a new untagged selection for \(e^+e^- \to \tau^+\tau^-\) events, where the signal \(\tau\) is searched for as a neutrinoless final state of a single charged lepton and a \(\phi\) meson and the other \(\tau\) is not reconstructed in any specific decay mode, in contrast to previous measurements by the BaBar and Belle experiments. We find no evidence for \(\tau^- \to \ell^- \phi\) decays and obtain upper limits on the branching fractions at 90% confidence level of 23 \(\times 10^{-8}\) and 9.7\(\times 10^{-8}\) for \(\tau^- \rightarrow e^-\phi\) and \(\tau^- \rightarrow \mu^-\phi\), respectively
The phase III AZA-001 study established that azacitidine significantly improves overall survival compared with conventional care regimens (hazard ratio 0.58 95% confidence interval 0.43-0.77, ...P<0.001). This analysis was conducted to investigate the relationship between treatment response and overall survival. AZA-001 data were analyzed in a multivariate Cox regression analysis with response as a time-varying covariate. Response categories were "Overall Response" (defined as complete remission, partial remission, or any hematologic improvement) and "Stable Disease" (no complete or partial remission, hematologic improvement, or progression) or "Other" (e.g. disease progression). Achieving an Overall Response with azacitidine reduced risk of death by 95% compared with achieving an Overall Response with the conventional care regimens (hazard ratio 0.05 95%CI: 0.01-0.43, P=0.006). Sensitivity analyses indicated that significantly improved overall survival remained manifest for patients with a hematologic improvement who had never achieved complete or partial remission (hazard ratio 0.19 95%CI: 0.08-0.46, P<0.001). Stable Disease in both azacitidine-treated and conventional care-treated patients was also associated with a significantly reduced risk of death (hazard ratio 0.09, 95%CI: 0.06-0.15; P<0.001). These results demonstrate azacitidine benefit on overall survival compared with conventional care regimens in patients with higher-risk myelodysplastic syndromes who achieve hematologic response but never attain complete or partial remission, in addition to the survival advantage conferred by achievement of complete or partial remission.
Phys. Rev. D 102, 052006 (2020) Based on 2.93~fb$^{-1}$ $e^+e^-$ collision data taken at center-of-mass
energy of 3.773 GeV by the BESIII detector, we report the measurements of the
absolute ...branching fractions of $D^0\to K^+K^-\pi^0\pi^0$, $D^0\to
K^0_SK^0_S\pi^+\pi^-$, $D^0\to K^0_SK^-\pi^+\pi^0$, $D^0\to
K^0_SK^+\pi^-\pi^0$, $D^+\to K^+K^-\pi^+\pi^0$, $D^+\to K^0_SK^+\pi^0\pi^0$,
$D^+\to K^0_SK^-\pi^+\pi^+$, $D^+\to K^0_SK^+\pi^+\pi^-$, and $D^+\to
K^0_SK^0_S\pi^+\pi^0$. The decays $D^0\to K^+K^-\pi^0\pi^0$, $D^0\to
K^0_SK^-\pi^+\pi^0$, $D^0\to K^0_SK^+\pi^-\pi^0$, $D^+\to
K^0_SK^0_S\pi^+\pi^0$, and $D^+\to K^0_SK^+\pi^0\pi^0$ are observed for the
first time. The branching fractions of the decays $D^0\to
K^0_SK^0_S\pi^+\pi^-$, $D^+\to K^+K^-\pi^+\pi^0$, $D^+\to K^0_SK^-\pi^+\pi^+$,
and $D^+\to K^0_SK^+\pi^+\pi^-$ are measured with improved precision compared
to the world-average values.
The aim of the study was to evaluate the in vitro antibacterial activity of glucosinolates and their enzymatic hydrolysis product against bacteria isolated from the human intestinal tract. Using a ...disc diffusion bioassay, different doses of intact glucosinolates and their corresponding hydrolysis products were tested. There were clear structure-activity and concentration differences with respect to the in vitro growth inhibition effects as well as differences in the sensitivities of the individual bacteria. The most effective glucosinolate hydrolysis products were the isothiocyanates; sulforaphane and benzyl isothiocyanate were the best inhibitors of growth. Indole-3-carbinol had some inhibitory effects against the Gram-positive bacteria but had no effect, even at the highest dose, against the Gram-negative bacteria. Indole-3-acetonitrile had some inhibitory activity against the Gram-negative bacteria. Glucosinolates, nitriles and amines were ineffective at all the doses used. Glucosinolate hydrolysis products and specifically the isothiocyanates SFN and BITC have significant antimicrobial activity against Gram-positive and Gram-negative bacteria, and might be useful in controlling human pathogens through the diet. This the first major in vitro study demonstrating the potential of these natural dietary chemicals as an alternative to, or in combination with, current antibiotic-based therapies for treating infectious diseases.
ABSTRACT We present Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) observations of the source and lens stars for planetary microlensing event OGLE-2005-BLG-169, which confirm the relative ...proper motion prediction due to the planetary light curve signal observed for this event. This (and the companion Keck result) provide the first confirmation of a planetary microlensing signal, for which the deviation was only 2%. The follow-up observations determine the flux of the planetary host star in multiple passbands and remove light curve model ambiguity caused by sparse sampling of part of the light curve. This leads to a precise determination of the properties of the OGLE-2005-BLG-169Lb planetary system. Combining the constraints from the microlensing light curve with the photometry and astrometry of the HST/WFC3 data, we find star and planet masses of and . The planetary microlens system is located toward the Galactic bulge at a distance of kpc and the projected star-planet separation is AU, corresponding to a semimajor axis of AU.
We measure the lifetime of the \(D_s^+\) meson using a data sample of 207 fb\(^{-1}\) collected by the Belle II experiment running at the SuperKEKB asymmetric-energy \(e^+ e^-\) collider. The ...lifetime is determined by fitting the decay-time distribution of a sample of \(116\times 10^3\) \(D_s^+\rightarrow\phi\pi^+\) decays. Our result is \(\tau^{}_{D^+_s} = (499.5\pm 1.7\pm 0.9)\) fs, where the first uncertainty is statistical and the second is systematic. This result is significantly more precise than previous measurements.
We report on first measurements of branching fractions~($\mathcal{B}$) and
CP-violating charge asymmetries~($\mathcal{A}$) in charmless $B$ decays at
Belle~II. We use a sample of electron-positron ...collisions collected in 2019 and
2020 at the $\Upsilon(4S)$ resonance and corresponding to $34.6$\,fb$^{-1}$ of
integrated luminosity. We use simulation to determine optimized event
selections. The $\Delta E$ distributions of the resulting samples, restricted
in $M_{\rm bc}$, are fit to determine signal yields. Signal yields are
corrected for efficiencies determined from simulation and control data samples
to obtain branching fractions and CP-violating asymmetries for flavour-specific
channels. These are the first measurements in charmless decays reported by
Belle~II. Results are compatible with known determinations and show detector
performance comparable with the best Belle results offering a reliable basis to
assess projections for future reach.
Howard Hughes Medical Institute and Departments of Cell
Biology and Biochemistry, Duke University Medical Center,
Durham, North Carolina; and Department of Biosciences, University of
Kent, ...Canterbury, United Kingdom
Bennett, Vann and
Anthony J. Baines.
Spectrin and Ankyrin-Based Pathways: Metazoan
Inventions for Integrating Cells Into Tissues. Physiol. Rev. 81: 1353-1392, 2001. The
spectrin-based membrane skeleton of the humble mammalian
erythrocyte has provided biologists with a set of interacting proteins
with diverse roles in organization and survival of cells in metazoan
organisms. This review deals with the molecular physiology of spectrin,
ankyrin, which links spectrin to the anion exchanger, and two
spectrin-associated proteins that promote spectrin interactions with actin: adducin and protein 4.1. The lack of essential functions for these proteins in generic cells grown in culture and the absence of
their genes in the yeast genome have, until recently, limited advances
in understanding their roles outside of erythrocytes. However,
completion of the genomes of simple metazoans and application of
homologous recombination in mice now are providing the first glimpses
of the full scope of physiological roles for spectrin, ankyrin, and
their associated proteins. These functions now include targeting of ion
channels and cell adhesion molecules to specialized compartments within
the plasma membrane and endoplasmic reticulum of striated muscle and
the nervous system, mechanical stabilization at the tissue level based
on transcellular protein assemblies, participation in epithelial
morphogenesis, and orientation of mitotic spindles in asymmetric cell
divisions. These studies, in addition to stretching the erythrocyte
paradigm beyond recognition, also are revealing novel cellular pathways
essential for metazoan life. Examples are ankyrin-dependent
targeting of proteins to excitable membrane domains in the plasma
membrane and the Ca 2+ homeostasis compartment of the
endoplasmic reticulum. Exciting questions for the future relate to the
molecular basis for these pathways and their roles in a clinical
context, either as the basis for disease or more positively as
therapeutic targets.
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