Compound heterozygosity of predicted loss-of-function DES variants in a family with recessive desminopathy

Background: Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established. Case presentation: Next-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent. Conclusions: This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies

Urban informality and confinement: toward a relational framework

In the 21st century, a growing number of people live ‘informal’ lives within fissures between legality and informality. Concomitantly, power relations are increasingly expressed through devices of confinement. While urban informality and confinement are on the rise often occurring simultaneously, scholars have so far studied them separately. By contrast, this article proposes a new framework for analysing urban informality and confinement relationally. It generates new insights into the role of informality in the (re)production of confinement and, vice versa, the role of confinement in shaping informal practices. While these insights are valuable for urban studies in general, the article charts new lines of research on urban marginality. It also discusses how the six articles included in this special issue signal the heuristic potential of this relational framework by empirically examining distinct urban configurations of ‘confined informalities’ and ‘informal confinements’ across the Global North and the Global South

The pressure-volume-temperature relationship of cellulose

Pressure–volume–temperature (PVT) mea- surements of a-cellulose with different water contents, were performed at temperatures from 25 to 180 °C and pressures from 19.6 to 196 MPa. PVT measurements allowed observation of the combined effects of pressure and temperature on the specific volume during cellulose thermo-compression. All isobars showed a decrease in cellulose specific volume with temperature. This densification is associated with a transition process of the cellulose, occurring at a temperature defined by the inflection point Tt of the isobar curve. Tt decreases from 110 to 40 °C with pressure and is lower as moisture content increases. For isobars obtained at high pressures and high moisture contents, after attaining a minimum, an increase in volume is observed with temperature that may be related to free water evaporation. PVT a-cellulose experimental data was compared with predicted values from a regression analysis of the Tait equations of state, usually applied to synthetic polymers. Good correla- tions were observed at low temperatures and low pressures. The densification observed from the PVT experimental data, at a temperature that decreases with pressure, could result from a sintering phenomenon, but more research is needed to actually understand the cohesion mechanism under these conditions

MeV-mass dark matter and primordial nucleosynthesis

The annihilation of new dark matter candidates with masses $m_X$ in the MeV range may account for the galactic positrons that are required to explain the 511 keV $\gamma$-ray flux from the galactic bulge. We study the impact of MeV-mass thermal relic particles on the primordial synthesis of $^2$H, $^4$He, and $^7$Li. If the new particles are in thermal equilibrium with neutrinos during the nucleosynthesis epoch they increase the helium mass fraction for m_X\alt 10 MeV and are thus disfavored. If they couple primarily to the electromagnetic plasma they can have the opposite effect of lowering both helium and deuterium. For $m_X=4$--10 MeV they can even improve the overall agreement between the predicted and observed $^2$H and $^4$He abundances.Comment: 11 pages, 10 figures, references and two appendices added, conclusions unchanged; accepted for publication in Phys.Rev.

Precision measurement of the neutron β-decay asymmetry

A new measurement of the neutron β-decay asymmetry A_0 has been carried out by the UCNA Collaboration using polarized ultracold neutrons (UCNs) from the solid deuterium UCN source at the Los Alamos Neutron Science Center. Improvements in the experiment have led to reductions in both statistical and systematic uncertainties leading to A_0=−0.11954(55)_(stat)(98)_(syst), corresponding to the ratio of axial-vector to vector coupling λ ≡ g_A/g_V = −1.2756(30)

Search for neutron dark decay: n → χ + e⁺e⁻

In January, 2018, Fornal and Grinstein proposed that a previously unobserved neutron decay branch to a dark matter particle (χ) could account for the discrepancy in the neutron lifetime observed in two different types of experiments. One of the possible final states discussed includes a single χ along with an e⁺e⁻ pair. We use data from the UCNA (Ultracold Neutron Asymmetry) experiment to set limits on this decay channel. Coincident electron-like events are detected with ∼ 4π acceptance using a pair of detectors that observe a volume of stored Ultracold Neutrons (UCNs). We use the timing information of coincidence events to select candidate dark sector particle decays by applying a timing calibration and selecting events within a physically-forbidden timing region for conventional n → p + e⁻ + ν̅_e decays. The summed kinetic energy (E_(e⁺e⁻)) from such events is reconstructed and used to set limits, as a function of the χ mass, on the branching fraction for this decay channel

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

New result for the neutron β\beta-asymmetry parameter A0A_0 from UCNA

The neutron $\beta$-decay asymmetry parameter $A_0$ defines the correlation between the spin of the neutron and the momentum of the emitted electron, which determines $\lambda=\frac{g_{A}}{g_{V}}$, the ratio of the axial-vector to vector weak coupling constants. The UCNA Experiment, located at the Ultracold Neutron facility at the Los Alamos Neutron Science Center, is the first to measure such a correlation coefficient using ultracold neutrons (UCN). Following improvements to the systematic uncertainties and increased statistics, we report the new result $A_0 = -0.12054(44)_{\mathrm{stat}}(68)_{\mathrm{syst}}$ which yields $\lambda\equiv \frac{g_{A}}{g_{V}}=-1.2783(22)$. Combination with the previous UCNA result and accounting for correlated systematic uncertainties produces $A_0=-0.12015(34)_{\mathrm{stat}}(63)_{\mathrm{syst}}$ and $\lambda\equiv \frac{g_{A}}{g_{V}}=-1.2772(20)$.Comment: 9 pages, 7 figures, updated to as-published versio

First direct constraints on Fierz interference in free-neutron β decay

Precision measurements of free-neutron β decay have been used to precisely constrain our understanding of the weak interaction. However, the neutron Fierz interference term b_n, which is particularly sensitive to beyond-standard-model tensor currents at the TeV scale, has thus far eluded measurement. Here we report the first direct constraints on this term, finding b_n=0.067±0.005_(stat)^(+0.090)_(−0.061)_(sys), consistent with the standard model. The uncertainty is dominated by absolute energy reconstruction and the linearity of the β spectrometer energy response