481 research outputs found
De novo and bi-allelic pathogenic variants in NARS1 cause neurodevelopmental delay due to toxic gain-of-function and partial loss-of-function effects
Aminoacyl-tRNA synthetases (ARSs) are ubiquitous, ancient enzymes that charge amino acids to cognate tRNA molecules, the essential first step of protein translation. Here, we describe 32 individuals from 21 families, presenting with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia, with de novo heterozygous and bi-allelic mutations in asparaginyl-tRNA synthetase (NARS1). We demonstrate a reduction in NARS1 mRNA expression as well as in NARS1 enzyme levels and activity in both individual fibroblasts and induced neural progenitor cells (iNPCs). Molecular modeling of the recessive c.1633C\u3eT (p.Arg545Cys) variant shows weaker spatial positioning and tRNA selectivity. We conclude that de novo and bi-allelic mutations in NARS1 are a significant cause of neurodevelopmental disease, where the mechanism for de novo variants could be toxic gain-of-function and for recessive variants, partial loss-of-function
Digynic triploidy: Utility and challenges of noninvasive prenatal testing
Low fraction fetal DNA in noninvasive prenatal testing in the context of fetal growth restriction and multiple congenital anomalies should alert medical professionals to the possibility of digynic triploidy. Single-nucleotide polymorphism microarray can detect the parental origin of triploidy and explain its mechanism
Nuclear Anapole Moments
Nuclear anapole moments are parity-odd, time-reversal-even E1 moments of the
electromagnetic current operator. Although the existence of this moment was
recognized theoretically soon after the discovery of parity nonconservation
(PNC), its experimental isolation was achieved only recently, when a new level
of precision was reached in a measurement of the hyperfine dependence of atomic
PNC in 133Cs. An important anapole moment bound in 205Tl also exists. In this
paper, we present the details of the first calculation of these anapole moments
in the framework commonly used in other studies of hadronic PNC, a meson
exchange potential that includes long-range pion exchange and enough degrees of
freedom to describe the five independent amplitudes induced by
short-range interactions. The resulting contributions of pi-, rho-, and
omega-exchange to the single-nucleon anapole moment, to parity admixtures in
the nuclear ground state, and to PNC exchange currents are evaluated, using
configuration-mixed shell-model wave functions. The experimental anapole moment
constraints on the PNC meson-nucleon coupling constants are derived and
compared with those from other tests of the hadronic weak interaction. While
the bounds obtained from the anapole moment results are consistent with the
broad ``reasonable ranges'' defined by theory, they are not in good agreement
with the constraints from the other experiments. We explore possible
explanations for the discrepancy and comment on the potential importance of new
experiments.Comment: 53 pages; 10 figures; revtex; submitted to Phys Rev
Simulation of impulse response for indoor visible light communications using 3D CAD models
n this article, a tool for simulating the channel impulse response for indoor visible light communications using 3D
computer-aided design (CAD) models is presented. The simulation tool is based on a previous Monte Carlo
ray-tracing algorithm for indoor infrared channel estimation, but including wavelength response evaluation. The 3D scene, or the simulation environment, can be defined using any CAD software in which the user specifies, in
addition to the setting geometry, the reflection characteristics of the surface materials as well as the structures of the emitters and receivers involved in the simulation. Also, in an effort to improve the computational efficiency, two optimizations are proposed. The first one consists of dividing the setting into cubic regions of equal size, which offers a calculation improvement of approximately 50% compared to not dividing the 3D scene into sub-regions. The second one involves the parallelization of the simulation algorithm, which provides a computational speed-up proportional to the number of processors used
Surface and Temporal Biosignatures
Recent discoveries of potentially habitable exoplanets have ignited the
prospect of spectroscopic investigations of exoplanet surfaces and atmospheres
for signs of life. This chapter provides an overview of potential surface and
temporal exoplanet biosignatures, reviewing Earth analogues and proposed
applications based on observations and models. The vegetation red-edge (VRE)
remains the most well-studied surface biosignature. Extensions of the VRE,
spectral "edges" produced in part by photosynthetic or nonphotosynthetic
pigments, may likewise present potential evidence of life. Polarization
signatures have the capacity to discriminate between biotic and abiotic "edge"
features in the face of false positives from band-gap generating material.
Temporal biosignatures -- modulations in measurable quantities such as gas
abundances (e.g., CO2), surface features, or emission of light (e.g.,
fluorescence, bioluminescence) that can be directly linked to the actions of a
biosphere -- are in general less well studied than surface or gaseous
biosignatures. However, remote observations of Earth's biosphere nonetheless
provide proofs of concept for these techniques and are reviewed here. Surface
and temporal biosignatures provide complementary information to gaseous
biosignatures, and while likely more challenging to observe, would contribute
information inaccessible from study of the time-averaged atmospheric
composition alone.Comment: 26 pages, 9 figures, review to appear in Handbook of Exoplanets.
Fixed figure conversion error
Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing
No abstract available
T Cells from Programmed Death-1 Deficient Mice Respond Poorly to Mycobacterium tuberculosis Infection
Programmed Death-1 (PD-1; CD279) receptor molecule is widely believed to be a negative regulator predominantly expressed by exhausted/activated mouse T cells. Upon interaction with its ligands, PD-L1 and PD-L2, PD-1 inhibits activation of T cells and cytokine production, which has been documented in various viral and fungal infections as well as in vitro studies. Therefore, inhibition of T cell responses by PD-1 resulted in disease resistance in a variety of mouse infection models studied heretofore.Here, we report that PD-1 deficient (PD-1(-/-)) mice infected with Mycobacterium tuberculosis (M. tb) H37Rv by the aerosol route have increased susceptibility as compared with their wild type littermates. Surprisingly, M. tb antigen-specific T cell proliferation was dramatically reduced in PD-1 deficient animals compared with wild-type littermates, and this was due to increased numbers of regulatory T cells (Tregs) and recruitment of mesenchymal stem cells. Furthermore, PD-1(-/-) mice exhibited decreases in the autophagy-induced LC3-B marker protein in macrophages.Our findings suggest that PD-1 does not play an inhibitory role during M. tb infection and instead promotes mycobacterial clearance in mice
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