Fornal and Grinstein recently proposed that the discrepancy between two different methods of neutron lifetime measurements, the beam and bottle methods, can be explained by a previously unobserved ...dark matter decay mode, n→X+γ. We perform a search for this decay mode over the allowed range of energies of the monoenergetic γ ray for X to be dark matter. A Compton-suppressed high-purity germanium detector is used to identify γ rays from neutron decay in a nickel-phosphorous-coated stainless-steel bottle. A combination of Monte Carlo and radioactive source calibrations is used to determine the absolute efficiency for detecting γ rays arising from the dark matter decay mode. We exclude the possibility of a sufficiently strong branch to explain the lifetime discrepancy with 97% confidence.
At least 5% of individuals with hypertension have adrenal aldosterone-producing adenomas (APAs). Gain-of-function mutations in KCNJ5 and apparent loss-of-function mutations in ATP1A1 and ATP2A3 were ...reported to occur in APAs. We find that KCNJ5 mutations are common in APAs resembling cortisol-secreting cells of the adrenal zona fasciculata but are absent in a subset of APAs resembling the aldosterone-secreting cells of the adrenal zona glomerulosa. We performed exome sequencing of ten zona glomerulosa-like APAs and identified nine with somatic mutations in either ATP1A1, encoding the Na(+)/K(+) ATPase α1 subunit, or CACNA1D, encoding Cav1.3. The ATP1A1 mutations all caused inward leak currents under physiological conditions, and the CACNA1D mutations induced a shift of voltage-dependent gating to more negative voltages, suppressed inactivation or increased currents. Many APAs with these mutations were <1 cm in diameter and had been overlooked on conventional adrenal imaging. Recognition of the distinct genotype and phenotype for this subset of APAs could facilitate diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This is the fifth in a series of papers studying the astrophysics and cosmology of massive, dynamically relaxed galaxy clusters. Our sample comprises 40 clusters identified as being dynamically ...relaxed and hot in Papers I and II of this series. Here we use constraints on cluster mass profiles from X-ray data to test some of the basic predictions of cosmological structure formation in the cold dark matter (CDM) paradigm. We present constraints on the concentration–mass relation for massive clusters, finding a power-law mass dependence with a slope of κ
m
= −0.16 ± 0.07, in agreement with CDM predictions. For this relaxed sample, the relation is consistent with a constant as a function of redshift (power-law slope with 1 + z of κζ = −0.17 ± 0.26), with an intrinsic scatter of σln c
= 0.16 ± 0.03. We investigate the shape of cluster mass profiles over the radial range probed by the data (typically ∼50 kpc–1 Mpc), and test for departures from the simple Navarro–Frenk–White (NFW) form, for which the logarithmic slope of the density profile tends to −1 at small radii. Specifically, we consider as alternatives the generalized NFW (GNFW) and Einasto parametrizations. For the GNFW model, we find an average value of (minus) the logarithmic inner slope of β = 1.02 ± 0.08, with an intrinsic scatter of σβ = 0.22 ± 0.07, while in the Einasto case we constrain the average shape parameter to be α = 0.29 ± 0.04 with an intrinsic scatter of σα = 0.12 ± 0.04. Our results are thus consistent with the simple NFW model on average, but we clearly detect the presence of intrinsic, cluster-to-cluster scatter about the average.
The only anticipated resonant contributions to B^{+}→D^{+}D^{-}K^{+} decays are charmonium states in the D^{+}D^{-} channel. A model-independent analysis, using LHCb proton-proton collision data ...taken at center-of-mass energies of sqrts=7, 8, and 13 TeV, corresponding to a total integrated luminosity of 9 fb^{-1}, is carried out to test this hypothesis. The description of the data assuming that resonances only manifest in decays to the D^{+}D^{-} pair is shown to be incomplete. This constitutes evidence for a new contribution to the decay, potentially one or more new charm-strange resonances in the D^{-}K^{+} channel with masses around 2.9 GeV/c^{2}.
Plastic changes in motor cortex capillary structure and function were examined in three separate experiments in adult rats following prolonged exercise. The first two experiments employed T-two-star ...(T
2*)-weighted and flow-alternating inversion recovery (FAIR) functional magnetic resonance imaging to assess chronic changes in blood volume and flow as a result of exercise. The third experiment used an antibody against the CD61 integrin expressed on developing capillaries to determine if motor cortex capillaries undergo structural modifications. In experiment 1, T
2*-weighted images of forelimb regions of motor cortex were obtained following 30 days of either repetitive activity on a running wheel or relative inactivity. The proton signal intensity was markedly reduced in the motor cortex of exercised animals compared with that of controls. This reduction was not attributable to alterations of vascular iron levels. These results are therefore most consistent with increased capillary perfusion or blood volume of forelimb regions of motor cortex. FAIR images acquired during experiment 2 under normocapnic and hypercapnic conditions indicated that resting cerebral blood flow was not altered under normal conditions but was elevated in response to high levels of CO
2, suggesting that prolonged exercise increases the size of a capillary reserve. Finally, the immunohistological data indicated that exercise induces robust growth of capillaries (angiogenesis) within 30 days from the onset of the exercise regimen. Analysis of other regions failed to find any changes in perfusion or capillary structure suggesting that this motor activity-induced plasticity may be specific to motor cortex.
These data indicate that capillary growth occurs in motor areas of the cerebral cortex as a robust adaptation to prolonged motor activity. In addition to capillary growth, the vascular system also experiences heightened flow under conditions of activation. These changes are chronic and observable even in the anesthetized animal and are measurable using noninvasive techniques.
Context:
Aldosterone-producing adenomas (APA) are heterogeneous. The recent finding of somatic KCNJ5 mutations suggests a genetic explanation.
Objectives:
The objectives of this study were the ...following: 1) to compare transcriptional profiles in APA and adjacent adrenal gland (AAG); 2) to test whether gene expression profile clusters with different cell histology; and 3) to measure the frequency of KCNJ5 mutations and determine the genotype-phenotype relationship.
Design/Setting:
The design of the study included laboratory analyses of 46 unselected APA.
Patients:
The patients in this study had primary hyperaldosteronism with unilateral APA.
Interventions:
The objectives of this study were the following: 1) Illumina beadchip analysis of RNA from eight paired APA-AAG; 2) a blinded review of cell histology for 46 APA; 3) laser capture microdissection of zona glomerulosa (ZG) and zona fasciculata (ZF) cells; and 4) sequencing of KCNJ5 in 46 APA.
Main Outcome Measures:
The main outcome measures of this study were the following: 1) a difference in gene expression profile and a correlation with histological markers of ZF; 2) a frequency of KCNJ5 mutations and phenotypic comparisons of wild type with mutant APA.
Results:
The results of the study were the following: 1) a cluster analysis of microarray data separated APA from AAG. APA at opposite ends of the APA cluster had an approximately 800-fold difference in CYP17A1 mRNA expression, whereas histology showed 0% ZF-like cells in one vs. 100% in the other. A heat map ranking APA by CYP17A1 expression correctly predicted several genes (e.g. KCNK1, SLC24A3) to be enriched in laser capture microdissection samples of ZG; 2) known or novel mutations of KCNJ5 were found in 20 of 46 consecutive APA 43% (95% confidence interval CI (29, 58)%). The APA with KCNJ5 gene mutations were larger compared with tumors harboring the wild type, 1.63 95% CI (1.37, 1.88) vs. 1.14 0.97, 1.30 cm (P = 0.0013), had predominantly ZF-like cells, and their CYP17A1 (log2-fold change) was higher than in wild type: −0.96 95% CI (−0.07, −1.85) vs. −2.54 −1.61, −3.46, (P = 0.017).
Conclusions:
KCNJ5 mutations are common in APA, particularly those arising from ZF. The long-recognized heterogeneity among APA may have a genetic basis.
Primary hyperaldosteronism, one cause of which is aldosterone-producing adenomas (APAs), may account for ≤5% to 10% of cases of essential hypertension. Germline mutations have been identified in 2 ...rare familial forms of primary hyperaldosteronism, but it has been reported recently that somatic mutations of the KCNJ5 gene, which encodes a potassium channel, are present in some sporadic nonsyndromic APAs. To address this further we screened 2 large collections of sporadic APAs from the United Kingdom and Australia (totalling 73) and found somatic mutations in the selectivity filter of KCNJ5 in 41% (95% CI31% to 53%) of the APAs (30 of 73). These included the previously noted nonsynonymous mutations, G151R and L158R, and an unreported 3-base deletion, delI157, in the region of the selectivity filter. APAs containing a somatic KCNJ5 mutation were significantly larger than those without (1.61 cm 95% CI1.39–1.83 cm versus 1.04 cm 95% CI0.91–1.17 cm; P<0.0001) but with substantial overlap in size between genotypes. The APAs carrying a mutation, but not those without, also consistently lacked a postural aldosterone response, suggesting a physiologically distinct subtype. Hence, somatic KCNJ5 mutations are not restricted to large APAs (>2 cm), and their frequency in our unselected series suggests they are common and could be important in the molecular pathogenesis of many sporadic cases of APA.
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