Identification of BACE1 cleavage sites in human voltage-gated sodium channel beta 2 subunit

<p>Abstract</p> <p>Background</p> <p>The voltage-gated sodium channel β2 subunit (Navβ2) is a physiological substrate of BACE1 (β-site APP cleaving enzyme) and γ-secretase, two proteolytic enzymes central to Alzheimer's disease pathogenesis. Previously, we have found that the processing of Navβ2 by BACE1 and γ-secretase regulates sodium channel metabolism in neuronal cells. In the current study we identified the BACE1 cleavage sites in human Navβ2.</p> <p>Results</p> <p>We found a major (147-148 L↓M, where ↓ indicates the cleavage site) and a minor (144145 L↓Q) BACE1 cleavage site in the extracellular domain of human Navβ2 using a cell-free BACE1 cleavage assay followed by mass spectrometry. Next, we introduced two different double mutations into the identified major BACE1 cleavage site in human Navβ2: 147LM/VI and 147LM/AA. Both mutations dramatically decreased the cleavage of human Navβ2 by endogenous BACE1 in cell-free BACE1 cleavage assays. Neither of the two mutations affected subcellular localization of Navβ2 as confirmed by confocal fluorescence microscopy and subcellular fractionation of cholesterol-rich domains. Finally, wildtype and mutated Navβ2 were expressed along BACE1 in B104 rat neuroblastoma cells. In spite of α-secretase still actively cleaving the mutant proteins, Navβ2 cleavage products decreased by ~50% in cells expressing Navβ2 (147LM/VI) and ~75% in cells expressing Navβ2 (147LM/AA) as compared to cells expressing wildtype Navβ2.</p> <p>Conclusion</p> <p>We identified a major (147-148 L↓M) and a minor (144-145 L↓Q) BACE1 cleavage site in human Navβ2. Our <it>in vitro </it>and cell-based results clearly show that the 147-148 L↓M is the major BACE1 cleavage site in human Navβ2. These findings expand our understanding of the role of BACE1 in voltage-gated sodium channel metabolism.</p

A Case Study of Assessing Button Bits Failure through Wavelet Transform Using Rock Drilling Induced Noise Signals

Finding the precise moment of button breakage of bits during drilling, with the experience of drill rig operators is a serious concern for modern vibrant mining industry. This research proposed a new methodology to find the failure of button using the sound generated by rock-bit interactions. The experiment is conducted by the video and sound data recorded during a drilling process in an underground mine, that uses a Sandvik AXERA7 twin boom jumbo drill rig and Polycrystalline diamond (PCD) tapered button bits. Signal analysis techniques such as Fourier transform and Wavelet transform are utilised to analyse the hectic noise signal recorded. The analysed results are shown that Wavelet Transform is much more effective in finding singularity points such as chipping or breakage of a button in compared to the Fourier Transform. The outcome of this analysis, which is the peak intensity at the breakage point, was correlated to the average intensity of the sound wave using moving average method. The results suggest that the noise generated during the drilling process can be used to detect the condition of the drill bit

Modeling and Analysis of a High-Displacement Pneumatic Artificial Muscle With Integrated Sensing

We present a high-displacement pneumatic artificial muscle made of textiles or plastics that can include integrated electronics to sense its pressure and displacement. Compared to traditional pneumatic muscle actuators such as the McKibben actuator and other more recent soft actuators, the actuator described in this paper can produce a much higher (40~65%) contraction ratio. In this paper, we describe the design, fabrication, and evaluation of the actuator, as well as the manufacturing process used to create it. We demonstrate the actuator design with several examples that produce 120 and 300 N at pressures of 35 and 105 kPa, respectively, and have contraction ratios of 40–65%

A multimedia data visualization based on Ad Hoc communication networks and its application to disaster management

After massive earthquakes and other large-scale disasters, existing communication infrastructure may become unavailable and, therefore, it can be quite difficult for relief organizations to fully grasp the impact of the disaster on the affected region. Consequently, this will be the cause of delays to offer the strategic assistance, and to provide water and food, etc. In order to solve the problem of re-establishing communication infrastructure to allow for information gathering, we developed an ad hoc mobile communications network for disaster-struck areas using ZigBee. As the communication speed of ZigBee is low, we propose a problem-specific image compression method for the multimedia data visualization. By using the proposed method combined with GPS information, it is possible to quickly grasp the damage situation in the region. Through our communication experiments in Tsukuba City, Japan we confirm the effectiveness of our system as a disaster information gathering and management system

Gravitational Wave Spectrum in Inflation with Nonclassical States

The initial quantum state during inflation may evolve to a highly squeezed quantum state due to the amplification of the time-dependent parameter, $\omega_{phys}(k/a)$, which may be the modified dispersion relation in trans-Planckian physics. This squeezed quantum state is a nonclassical state that has no counterpart in the classical theory. We have considered the nonclassical states such as squeezed, squeezed coherent, and squeezed thermal states, and calculated the power spectrum of the gravitational wave perturbation when the mode leaves the horizon.Comment: 21 page

Carrier-envelope phase effects on the strong-field photoemission of electrons from metallic nanostructures

Sharp metallic nanotapers irradiated with few-cycle laser pulses are emerging as a source of highly confined coherent electron wavepackets with attosecond duration and strong directivity. The possibility to steer, control or switch such electron wavepackets by light is expected to pave the way towards direct visualization of nanoplasmonic field dynamics and real-time probing of electron motion in solid state nanostructures. Such pulses can be generated by strong-field induced tunneling and acceleration of electrons in the near-field of sharp gold tapers within one half-cycle of the driving laser field. Here, we show the effect of the carrier-envelope phase of the laser field on the generation and motion of strong-field emitted electrons from such tips. This is a step forward towards controlling the coherent electron motion in and around metallic nanostructures on ultrashort length and time scales

The Association between Disturbed Eating Behavior and Socioeconomic Status: The Online Korean Adolescent Panel Survey (OnKAPS)

Background: A limited amount of research, primarily conducted in Western countries, has suggested that higher socioeconomic status (SES) is associated with higher risk of eating disorders (EDs). However, little is known about this association in Asian countries. We examined the association of SES with disturbed eating behavior (DEB) and related factors in Korean adolescents. Subjects A nationwide online panel survey was conducted in a sample of adolescents (n = 6,943, 49.9% girls). DEB was measured with the 26-item Eating Attitudes Test (EAT-26). Participants who scored ≥20 on the EAT-26 were considered to have DEB. Participants’ SES was determined based on self-reported household economic status. Results: The prevalence of DEB was 12.7%: 10.5% among boys and 14.8% among girls. Both boys and girls with DEB were more likely to perceive themselves as obese, experience higher levels of stress, and have lower academic achievement. The risk for DEB was significantly higher in boys of higher SES than in those of middle SES (OR = 1.45, 95%CI = 1.05–1.99 for high SES; OR = 5.16, 95%CI: 3.50–7.61 for highest SES). Among girls, higher risk of DEB was associated with the highest and lowest SES (OR = 1.52, 95%CI: 1.13–2.06 for lowest SES; OR = 2.22, 95%CI: 1.34–3.68 for highest SES). Conclusions: Despite the lower prevalence of obesity in Korea compared with Western countries, the prevalence of DEB in Korean adolescents was high, especially among girls. Moreover, the association between SES and DEB followed a U-shaped curve for girls and a J-shaped curve for boys

Global declines in coral reef calcium carbonate production under ocean acidification and warming

Ocean warming and acidification threaten the future growth of coral reefs. This is because the calcifying coral reef taxa that construct the calcium carbonate frameworks and cement the reef together are highly sensitive to ocean warming and acidification. However, the global-scale effects of ocean warming and acidification on rates of coral reef net carbonate production remain poorly constrained despite a wealth of studies assessing their effects on the calcification of individual organisms. Here, we present global estimates of projected future changes in coral reef net carbonate production under ocean warming and acidification. We apply a meta-analysis of responses of coral reef taxa calcification and bioerosion rates to predicted changes in coral cover driven by climate change to estimate the net carbonate production rates of 183 reefs worldwide by 2050 and 2100. We forecast mean global reef net carbonate production under representative concentration pathways (RCP) 2.6, 4.5, and 8.5 will decline by 76, 149, and 156%, respectively, by 2100. While 63% of reefs are projected to continue to accrete by 2100 under RCP2.6, 94% will be eroding by 2050 under RCP8.5, and no reefs will continue to accrete at rates matching projected sea level rise under RCP4.5 or 8.5 by 2100. Projected reduced coral cover due to bleaching events predominately drives these declines rather than the direct physiological impacts of ocean warming and acidification on calcification or bioerosion. Presently degraded reefs were also more sensitive in our analysis. These findings highlight the low likelihood that the world’s coral reefs will maintain their functional roles without near-term stabilization of atmospheric CO2 emissions

A novel c.-22T>C mutation in GALK1 promoter is associated with elevated galactokinase phenotype

<p>Abstract</p> <p>Background</p> <p>Many genetic variations of <it>GALK1 </it>have been identified in the patients with galactokinase (GALK1) deficiency. However, the molecular characteristics of <it>GALK1 </it>in individuals with elevated GALK1 activity are relatively unknown.</p> <p>Methods</p> <p>We investigated the relationship between elevated GALK1 activity and the molecular <it>GALK1 </it>gene variations, and the molecular mechanism underlying elevated GALK1 activity. PCR products from 63 subjects, without any attenuation of galactose degradation enzymes, were sequenced to screen for nucleotide alterations in the <it>GALK1 </it>promoter.</p> <p>Results</p> <p>Three nucleotide substitutions were identified: c.-179A>G, c.-27A>C, and c.-22T>C. With respect to the c.-22T>C mutation, GALK1 activity in 13 subjects with the T/C or C/C genotype was significantly higher than those in 50 subjects with the T/T genotype (p < 0.001). The dual luciferase reporter assay in Hep3B cells showed that the luciferase activity with the <it>GALK1 </it>promoter with the c.-22C mutant allele increased approximately 2.5-fold, compared to that with the c.-22T. A specific DNA-protein complex was observed in an electrophoretic mobility shift assay, with slightly higher affinity to c.-22C than to c.-22T.</p> <p>Conclusion</p> <p>The c.-22T>C mutation, which was observed frequently in individuals with elevated GALK1 activity, increased the expression of a reporter gene through enhanced binding of a currently unidentified nuclear protein. These results suggest that the elevated GALK1 activity resulted from enhanced gene expression, due to nucleotide variation within <it>GALK1 </it>promoter.</p

ASB9 interacts with ubiquitous mitochondrial creatine kinase and inhibits mitochondrial function

<p>Abstract</p> <p>Background</p> <p>The ankyrin repeat and suppressor of cytokine signalling (SOCS) box proteins (Asbs) are a large protein family implicated in diverse biological processes including regulation of proliferation and differentiation. The SOCS box of Asb proteins is important in a ubiquitination-mediated proteolysis pathway. Here, we aimed to evaluate expression and function of human Asb-9 (ASB9).</p> <p>Results</p> <p>We found that a variant of ASB9 that lacks the SOCS box (ASB9ΔSOCS) was naturally detected in human cell lines but not in peripheral blood mononuclear cells or normal hepatocytes. We also identified ubiquitous mitochondrial creatine kinase (uMtCK) as a new target of ASB9 in human embryonic kidney 293 (HEK293) cells. The ankyrin repeat domains of ASB9 can associate with the substrate binding site of uMtCK in a SOCS box-independent manner. The overexpression of ASB9, but not ASB9ΔSOCS, induces ubiquitination of uMtCK. ASB9 and ASB9ΔSOCS can interact and colocalise with uMtCK in the mitochondria. However, only expression of ASB9 induced abnormal mitochondrial structure and a decrease of mitochondrial membrane potential. Furthermore, the creatine kinase activities and cell growth were significantly reduced by ASB9 but not by ASB9ΔSOCS.</p> <p>Conclusions</p> <p>ASB9 interacts with the creatine kinase system and negatively regulates cell growth. The differential expression and function of ASB9 and ASB9ΔSOCS may be a key factor in the growth of human cell lines and primary cells.</p