Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C.

VLGR1 (very large G protein-coupled receptor 1), also known as MASS1 (monogenic audiogenic seizure susceptible 1), is an orphan G protein-coupled receptor that contains a large extracellular N terminus with 35 calcium-binding domains. A truncating mutation in the Mass1 gene causes autosomal recessive, sound-induced seizures in the Frings mouse. However, the function of MASS1 and the mechanism underlying Frings mouse epilepsy are not known. Here, we found that MASS1 protein is enriched in the myelinated regions of the superior and inferior colliculi, critical areas for the initiation and propagation of audiogenic seizures. Using a panel of myelin antibodies, we discovered that myelin-associated glycoprotein (MAG) expression is dramatically decreased in Frings mice. MASS1 inhibits the ubiquitylation of MAG, thus enhancing the stability of this protein, and the calcium-binding domains of MASS1 are essential for this regulation. Furthermore, MASS1 interacts with Gαs/Gαq and activates PKA and PKC in response to extracellular calcium. Suppression of signaling by MASS1 RNAi or a specific inhibitor abrogates MAG up-regulation. We postulate that MASS1 senses extracellular calcium and activates cytosolic PKA/PKC pathways to regulate myelination by means of MAG protein stability in myelin-forming cells of the auditory pathway. Further work is required to determine whether MAG dysregulation is a cause or consequence of audiogenic epilepsy and whether there are other pathways regulated by MASS1

Minimum Required Distance of Strain Gauge from Specimen for Measuring Transmitted Signal in Split Hopkinson Pressure Bar Test

The minimum required distance of the strain gauge on the transmitted bar of the split Hopkinson bar has been determined from the position of a metallic specimen via an explicit finite element analysis. The minimum required distance was determined when the strain-time profiles at r = 0, 0.5Ro and 1.0Ro, were coincident (r is the radial position and Ro is the radius of the bar.). The determined minimum required distance, f(x), is presented as a function of the relative specimen diameter to that of the bar (x = D/D0): j(x) = - 0.9385.x3 + 0.6624.x2 - 0.7459.x + 1.4478 (0.1 ≤ x ≤ 0.9). This result demonstrates the Saint-Venant's principle of rapid dissipation of localized stress in transient loading. The result will be useful for the design/modification of the pseudo-one-dimensional impact instruments that utilise a stress pulse transmitted through the specimen. The result will also allow one to avoid unnecessarily remote strain gage position from the specimen

A splice variant acquiring an extra transcript leader region decreases the translation of glutamine synthetase gene.

The expression of glutamine synthetase (GS), catalysing the ATP-dependent conversion of glutamate and ammonia into glutamine, is transcriptionally and post-transcriptionally regulated. The genomic structure of dog GS shown in the present study is basically similar to that of other mammals in that it is composed of seven exons and six introns. Using 5'-cRACE (where cRACE stands for circular rapid amplification of cDNA ends) and reverse transcriptase-PCR, we identified an additional exon (120 bp) in the first intron, designated in the present study as exon 1'. By means of alternative splicing, the GS gene produces an altered form of GS transcript with 5'-untranslated region (UTR) containing the exon 1'. This alternative transcript is abundantly expressed in brain, whereas it is found at lower levels in other tissues. In the human and mouse GS genes, extra exons are also found at the corresponding site of the intron 1 but with different sizes. An exon-trapping experiment for the GS gene in COS-7, Madin-Darby canine kidney and SK-N-SH cells revealed that the pattern of alternative splicing is variable in different cell types. The propensity of forming a secondary structure is predicted to be considerably higher in the presence of extra 5'-UTR, suggesting the possibility of a translational effect. To test this, we performed a reporter assay for fusions with different 5'-UTRs, demonstrating that the long form with extra 5'-UTR was translated 20- and 10-fold less than the short one in SK-N-SH and Neuro-2A cells respectively. Similarly, translations of human and mouse transcripts with extra 5'-UTRs were less efficient, showing 6-8-fold reductions in SK-N-SH cells. Furthermore, when we mutated an ATG sequence contained in the exon 1', the suppression of translation was partially relieved, suggesting that the negative regulation by an extra 5'-UTR is, to some extent, due to an abortive translation from the upstream ATG

Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C.

VLGR1 (very large G protein-coupled receptor 1), also known as MASS1 (monogenic audiogenic seizure susceptible 1), is an orphan G protein-coupled receptor that contains a large extracellular N terminus with 35 calcium-binding domains. A truncating mutation in the Mass1 gene causes autosomal recessive, sound-induced seizures in the Frings mouse. However, the function of MASS1 and the mechanism underlying Frings mouse epilepsy are not known. Here, we found that MASS1 protein is enriched in the myelinated regions of the superior and inferior colliculi, critical areas for the initiation and propagation of audiogenic seizures. Using a panel of myelin antibodies, we discovered that myelin-associated glycoprotein (MAG) expression is dramatically decreased in Frings mice. MASS1 inhibits the ubiquitylation of MAG, thus enhancing the stability of this protein, and the calcium-binding domains of MASS1 are essential for this regulation. Furthermore, MASS1 interacts with Gαs/Gαq and activates PKA and PKC in response to extracellular calcium. Suppression of signaling by MASS1 RNAi or a specific inhibitor abrogates MAG up-regulation. We postulate that MASS1 senses extracellular calcium and activates cytosolic PKA/PKC pathways to regulate myelination by means of MAG protein stability in myelin-forming cells of the auditory pathway. Further work is required to determine whether MAG dysregulation is a cause or consequence of audiogenic epilepsy and whether there are other pathways regulated by MASS1

Security Enhancement for Smartphone Using Biometrics in Cyber-Physical Systems

With the expansion of the Cyber-Physical System (CPS) concept, smartphones have come to constitute a competitive platform that connects humans and the surrounding physical world. Along with the communication functions and mobility of cellular phones, smartphones have various sensors in addition to greatly enhanced performances and storage space compared with existing cellular phones. However the “unlock” process of smartphones and the need for user passwords when accessing SNSs prove to be great weaknesses in smartphone security. Therefore, smartphone security should be enhanced through biometrics, which can make up for the shortcomings of passwords. The present study proposes minutiae-ridge based fingerprint verification for enhancing the security of fingerprint verification, a biometrics, to improve smartphone security. To evaluate the proposed minutiae-ridge based fingerprint verification performance in smartphones, its performance was compared with existing fingerprint verification methods in terms of Equal Error Rate (EER), False Non-Match Rate (FNMR), and required number of cycles. The results show that although the required number of cycles increased by 1.5% with the proposed method, EER and FNMR improved by 53% and 92%, respectively

Ribose Utilization with an Excess of Mutarotase Causes Cell Death Due to Accumulation of Methylglyoxal

Methylglyoxal (MG) is a highly reactive metabolic intermediate, presumably accumulated during uncontrolled carbohydrate metabolism. The major source of MG is dihydroxyacetone phosphate, which is catalyzed by MG synthase (the mgs product) in bacteria. We observed Escherichia coli cell death when the ribose transport system, consisting of the RbsDACBK proteins, was overproduced on multicopy plasmids. Almost 100% of cell death occurs a few hours after ribose addition (>10 mM), due to an accumulation of extracellular MG as detected by (1)H-nuclear magnetic resonance ((1)H-NMR). Under lethal conditions, the concentration of MG produced in the medium reached approximately 1 mM after 4 h of ribose addition as measured by high-performance liquid chromatography. An excess of the protein RbsD, recently characterized as a mutarotase that catalyzes the conversion between the β-pyran and β-furan forms of ribose, was critical in accumulating the lethal level of MG, which was also shown to require ribokinase (RbsK). The intracellular level of ribose 5-phosphate increased with the presence of the protein RbsD, as determined by (31)P-NMR. As expected, a mutation in the methylglyoxal synthase gene (mgs) abolished the production of MG. These results indicate that the enhanced ribose uptake and incorporation lead to an accumulation of MG, perhaps occurring via the pentose-phosphate pathway and via glycolysis with the intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate. It was also demonstrated that a small amount of MG is synthesized by monoamine oxidase

High Accuracy Open-Type Current Sensor with a Differential Planar Hall Resistive Sensor

In this paper, we propose a high accuracy open-type current sensor with a differential Planar Hall Resistive (PHR) sensor. Conventional open-type current sensors with magnetic sensors are usually vulnerable to interference from an external magnetic field. To reduce the effect of an unintended magnetic field, the proposed design uses a differential structure with PHR. The differential structure provides robust performance to unwanted magnetic flux and increased magnetic sensitivity. In addition, instead of conventional Hall sensors with a magnetic concentrator, a newly developed PHR with high sensitivity is employed to sense horizontal magnetic fields. The PHR sensor and read-out integrated circuit (IC) are integrated through a post-Complementary metal-oxide-semiconductor (CMOS) process using multi-chip packaging. The current sensor is designed to measure a 1 A current level. The measured performance of the designed current sensor has a 16 kHz bandwidth and a current nonlinearity of under ±0.5%

Brainstem development requires galactosylceramidase and is critical for pathogenesis in a model of Krabbe disease

Krabbe disease is caused by GALC deficiency, leading to accumulation of cytotoxic psychosine, demyelination, and neurodegeneration. Here, the authors develop a Galc flox mouse line to model Krabbe disease and unveil that early postnatal GALC neuronal expression is critical for disease pathogenesis

Plasmonic Optical Interference

Understanding optical interference is of great importance in fundamental and analytical optical design for next-generation personal, industrial, and military applications. So far, various researches have been performed for optical interference phenomena, but there have been no reports on plasmonic optical interference. Here, we report that optical interference could be effectively coupled with surface plasmons, resulting in enhanced optical absorption. We prepared a three-dimensional (3D) plasmonic nanostructure that consists of a plasmonic layer at the top, a nanoporous dielectric layer at the center, and a mirror layer at the bottom. The plasmonic layer mediates strong plasmonic absorption when the constructive interference pattern is matched with the plasmonic component. By tailoring the thickness of the dielectric layer, the strong plasmonic absorption can facilely be controlled and covers the full visible range. The plasmonic interference in the 3D nanostructure thus creates brilliant structural colors. We develop a design equation to determine the thickness of the dielectric layer in a 3D plasmonic nanostructure that could create the maximum absorption at a given wavelength. It is further demonstrated that the 3D plasmonic nanostructure can be realized on a flexible substrate. Our 3D plasmonic nanostructures will have a huge impact on the fields of optoelectronic systems, biochemical optical sensors, and spectral imaging