The role of tRNA synthetases in neurological and neuromuscular disorders.

Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for charging tRNAs with their cognate amino acids, therefore essential for the first step in protein synthesis. Although the majority of protein synthesis happens in the cytosol, an additional translation apparatus is required to translate the 13 mitochondrial DNA-encoded proteins important for oxidative phosphorylation. Most ARS genes in these cellular compartments are distinct, but two genes are common, encoding aminoacyl-tRNA synthetases of glycine (GARS) and lysine (KARS) in both mitochondria and the cytosol. Mutations in the majority of the 37 nuclear-encoded human ARS genes have been linked to a variety of recessive and dominant tissue-specific disorders. Current data indicate that impaired enzyme function could explain the pathogenicity, however not all pathogenic ARSs mutations result in deficient catalytic function; thus, the consequences of mutations may arise from other molecular mechanisms. The peripheral nerves are frequently affected, as illustrated by the high number of mutations in cytosolic and bifunctional tRNA synthetases causing Charcot-Marie-Tooth disease (CMT). Here we provide insights on the pathomechanisms of CMT-causing tRNA synthetases with specific focus on the two bifunctional tRNA synthetases (GARS, KARS)

Cubesat Laser Communications Transceiver for Multi-Gbps Downlink

Fibertek is developing a cubesat laser communications (lasercom) downlink terminal that supports direct optical data downlink from cubesats to modest optical ground stations with 30 to 50 cm diameter telescopes. This paper describes the design, development, and lab testing of the optical transceiver portion of a compact cubesat space lasercom terminal. The design uses a relatively large aperture, low divergence, and accurate pointing approach to minimize the required laser power as well as the overall electrical power of the system. The optical transceiver has a shared transmit/receive optical path that uses a 1 um laser beacon to ensure high pointing accuracy, control the pointing stability, and ensure a strong optical signal-to-noise ratio (SNR) during link operation. The fundamental terminal optical design has been manufactured and tested providing high accuracy pointing and low jitter. The systems design is completed by adding a cubesat form-factor 1.5-um fiber-amplifier with 2 W optical power, high-data-rate optical transceiver card, and digital-modem/bus-interface card to lasercom terminal capable of supporting \u3e5 Gbit/sec optical downlink

Advances in CubeSat Laser Communications Transceiver

This paper describes progress toward supporting full duplex Earth-to-ground links and intersatellite links (ISLs) capable of supporting mesh networks around Earth, the sun, and deep space. The paper reviews recent advances in compact free space optical (FSO) terminals at Fibertek and potential uses for a NASA Science Enabling Technologies for Heliophysics (SETH) mission and ISLs in general. The laser communications terminal (LCT) design is modular, flexible, and can accommodate a variety of waveforms and data formats. Fibertek has a unit deployed in space for initial testing to be followed by additional units for more broad-based market applications. Our first-generation optical telescope assembly was originally designed for NASA Deep Space CubeSat laser communications. It was customized as a complete commercial low Earth orbit (LEO) LCT system which is 2U in size, 2.5 kg in mass, and provides Gbps data rates. The optical transceiver has a shared transmit/receive optical path that uses a laser beacon to ensure high pointing accuracy, active control of the pointing stability, and a strong optical signal-to-noise ratio (SNR) during link operation. The terminal has been manufactured and tested, providing high-accuracy pointing and low jitter. Our second generation LCT system features bi-directional operation and support for an eye-safe beacon for uplink applications. Bi-directional operation is attractive for ISLs; uplinks of data; pointing, acquisition, and tracking (PAT); position, navigation, and timing (PNT); and telemetry, tracking, and command (TT&C). The eye-safe uplink beacon makes it easier to get FCC authorization for operation. The LCT includes a 64 mm telescope and a 1.5-μm fiber amplifier with \u3e2 W optical power that enables future updates to allow operation up to geosynchronous Earth orbit (GEO) and deep space

Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I

Small nuclear RNAs (snRNAs) are essential factors in messenger RNA splicing. By means of homozygosity mapping and deep sequencing, we show that a gene encoding U4atac snRNA, a component of the minor U12-dependent spliceosome, is mutated in individuals with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), a severe developmental disorder characterized by extreme intrauterine growth retardation and multiple organ abnormalities. Functional assays showed that mutations (30G>A, 51G>A, 55G>A, and 111G>A) associated with MOPD I cause defective U12-dependent splicing. Endogenous U12-dependent but not U2-dependent introns were found to be poorly spliced in MOPD I patient fibroblast cells. The introduction of wild-type U4atac snRNA into MOPD I cells enhanced U12-dependent splicing. These results illustrate the critical role of minor intron splicing in human development.Huiling He... Eric Haan... et al