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AimsTo assess the repeatability and reproducibility of the ocular measurements obtained with the Suoer SW-9000 μm Plus, a new fully automatic biometer based on optical low coherence reflectometry (OLCR) biometer, and to compare them to those obtained by a swept-source optical coherence tomography (SS-OCT)-based biometer.MethodsThis prospective study consisted of 115 eyes of 115 healthy subjects. The measurements were taken by the two optical biometers in random order. The measured parameters were axial length (AL), central corneal thickness (CCT), aqueous depth (AQD), anterior chamber depth (ACD), mean keratometry (Km), lens thickness (LT) and corneal diameter (CD). To evaluate the intraobserver repeatability and interobserver reproducibility, the within-subject SD, test–retest variability, coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were adopted. The Bland-Altman plot was drawn to assess the agreement.ResultsThe repeatability and reproducibility of all parameters for the new device were excellent (ICC>0.960 and CoVConclusionsThe new Suoer SW-9000 μm Plus biometer showed excellent repeatability and reproducibility. All the parameters obtained by this biometer were similar to those measured by SS-OCT-based biometer.

Income inequality plays as a driver of direct and indirect CO2 emissions from the household sector. Existing research has done a lot of work on the accounting methods and influencing factors of household direct CO2 emissions and indirect CO2 emissions. There are few studies on the impact of income inequality on direct and indirect household CO2 emissions under different emission levels. This research investigates the impact of income inequality on both direct and indirect CO2 emissions of 30 provinces in China from 2000 to 2015 using the STIRPAT model and panel quantile regression method. Theil index is selected to measure income inequality, population, per capita consumption level, energy intensity, urbanization, and industrial structure as control variables. The results indicate that the level of regional inequality is gradually increasing from the east to the west. The household indirect CO2 emissions in the east increased fastest, while the household direct CO2 emissions in the west increased fastest. Income inequality significantly promoted direct CO2 emissions under all quantile levels, while the impact on indirect CO2 emissions is not significant. Population and per capita consumption will promote direct and indirect CO2 emissions. Urbanization has no significant impact on direct CO2 emissions. Only at the 90th percentile level is there a significant negative correlation between energy intensity and indirect CO2 emissions. Industrial structure significantly increases direct CO2 emissions at the 50th, 75th, and 90th percentiles, while the impact on indirect CO2 emissions is not significant.

BACKGROUND: To analyze the imaging features of coronary artery-to-pulmonary artery fistula (CPAF) on coronary computed tomography angiography (CCTA). METHODS: This was a retrospective study of 3,975 patients who underwent 320 row detector CCTA examinations in our hospital from May 2015 to July 2020. A total of 22 patients who diagnosed with CPAF were reviewed for CCTA imaging characteristics, including the origin, number, blood volume, opening size, and course of fistula vessels, and the drainage site, size, and imaging features of the fistula. All cases were analyzed for the presence of coronary atherosclerotic plaque and that of deficient left ventricular myocardial perfusion. RESULTS: A total of 22 CPAF cases detected by CCTA were collected (men, 11; women, 11; median age, 59.6±10.1 years). There were 7, 10, and 5 cases detected with 1, 2, and 3 fistula vessels, respectively, among which 4 originated from the left coronary artery, 4 from the right coronary artery, and 14 had bilateral origins. There were 10 cases in which the fistula vessels presented as a worm-like tortuous dilation with (n=5) or without (n=5) aneurysm, while 12 cases showed malformed vascular networks with (n=8) or without (n=4) aneurysm, respectively. The calculated incidence of aneurysm formation was 59.09%, and fistula vessels with an aneurysm had larger blood volume than those without. All fistula showed a single drainage site, with an average diameter of 2.81±1.48 mm where the diameter of fistula with aneurysm was larger than that without. The fistula vessels drained into the left anterolateral and anterior walls of main pulmonary artery and the proximal left inferior PA, respectively. Typical jet sign, smoke sign, and isodensity sign were presented in 22, 14 and 1 case, respectively. For the coexistent abnormalities analyzed in 22 cases, 17 participants with CPAF demonstrated hypoperfusion of the fistula vessels, and 11 demonstrated calcified plaque accompanied with luminal stenosis to different degrees. CONCLUSIONS: The 320-row detector CCTA can comprehensively characterize the morphological features of CPAF, which is an optimal choice for physicians to make an accurate assessment before formulating patient management strategies.

Calpains are calcium-dependent, cytosolic proteinases active at neutral pH. They do not degrade but cleave substrates at limited sites. Calpains are implicated in various pathologies, such as ischemia, injuries, muscular dystrophy, and neurodegeneration. Despite so, the physiological function of calpains remains to be clearly defined. Using the neuromuscular junction ofDrosophilaof both sexes as a model, we performed RNAi screening and uncovered that calpains negatively regulated protein levels of the glutamate receptor GluRIIA but not GluRIIB. We then showed that calpains enrich at the postsynaptic area, and the calcium-dependent activation of calpains induced cleavage of GluRIIA at Q788 of its C terminus. Further genetic and biochemical experiments revealed that different calpains genetically and physically interact to form a protein complex. The protein complex was required for the proteinase activation to downregulate GluRIIA. Our data provide a novel insight into the mechanisms by which different calpains act together as a complex to specifically control GluRIIA levels and consequently synaptic function.SIGNIFICANCE STATEMENTCalpain has been implicated in neural insults and neurodegeneration. However, the physiological function of calpains in the nervous system remains to be defined. Here, we show that calpain enriches at the postsynaptic area and negatively and specifically regulates GluRIIA, but not IIB, level during development. Calcium-dependent activation of calpain cleaves GluRIIA at Q788 of its C terminus. Different calpains constitute an active protease complex to cleave its target. This study reveals a critical role of calpains during development to specifically cleave GluRIIA at synapses and consequently regulate synaptic function.

Calpains are evolutionarily conserved and widely expressed Ca2+-activated cysteine proteases that act at neutral pH. The activity of calpains is tightly regulated, given that their abnormal activation can have deleterious effects leading to promiscuous cleavage of various targets. Genetic mutations in the genes encoding calpains are associated with human diseases, while abnormally elevated Ca2+ levels promote Ca2+-dependent calpain activation in pathologies associated with ischemic insults and neurodegeneration. In this review, we discuss recent findings on the regulation of calpain activity and activation as revealed through pharmacological, genetic, and optogenetic approaches. Furthermore, we highlight studies elucidating the role of calpains in dendrite pruning and axon degeneration in the context of Ca2+ homeostasis. Finally, we discuss future directions for the study of calpains and potential therapeutic strategies for inhibiting calpain activity in neurodegenerative diseases.

1 + X certificate system is to connect and integrate the academic certificate reflecting the socialization level and several kinds of vocational skill level certificate reflecting the comprehensive ability level of enterprise occupation post. By referring to the national vocational post skill standard, the school and the enterprise cooperate deeply, and the teachers and enterprise tutors jointly teach, and focus on the cultivation of students' post skills. With the exploration of 1 + X certificate system pilot project, Ningbo Vocational and technical college adopts the course mode based on enterprise working process and school enterprise cooperation to reform the course of "mechanical processing technology". It takes enterprise selected project as the work task of students, takes the machining of mechanical parts as the core, and combines the processing of typical parts with the actual working post of the enterprise and the national vocational post skills The combination of the post qualification and the national vocational standards should be emphasized.

The Chinese government's hierarchical management of industrial development zones has an important impact on economic development and land use. However, the impact mechanism of rank different of development zones on land use efficiency is still unclear. This study summarizes the institutional differences between the national and provincial industrial development zones in preferential policies, strategic status, industry layout, and management systems. Based on the estimation of land use efficiency of 120 industrial development zones in Jiangsu Province, this paper uses panel data regression model to explore the impact of rank difference of industrial development zone on land use efficiency. The results indicate that there are significant differences in land use efficiency between different ranks of industrial development zones. The industrial land of national industrial development zones is much more efficient than that of provincial industrial development zones. The efficiency of national industrial development zones in southern Jiangsu is far higher than that in the other two regions. Except for Seaside and Riverside Development Zones, the rank of industrial development zone has a significant positive impact on land use efficiency. The type, age and water resource condition of industrial development zones can contribute to promoting land use efficiency. Regional economic development and traffic accessibility also have a positive impact on land use efficiency.

In needle coke industry, the raffinate oil from raw material refining could be used for co-carbonization to improve the structural evolution of aromatic feedstock with high aromaticity and low alkyl side chain content. High-temperature coal tar pitch (HCTP) and raffinate oil obtained from low-temperature coal tar (LCT) were used to prepare needle coke by liquid phase carbonization, and the characteristics of carbonization behavior as well as the structural evolution of blended materials were also investigated. The raffinate oil possessed abundant saturated compositions and the aromatic component distribution mainly concentrated in 1–3 cyclic aromatic hydrocarbons which resulted in a low yield of derived products and the carbonaceous sheets with poor planarity. Raffinate oil provided sufficient small molecular volatiles of alkyl radicals and generated abundant active sites for the polycondensation of HCTP with high aromaticity and low alkyl side chain content during co-carbonization. The addition of raffinate oil in HCTP facilitated the elimination of steric hindrance and healed the structural defects within the planar aromatic lamellae. This paper improved the utilization of raw material refining treatment and optimized the industrial structure of the needle coke preparation process.

Mold growth, one of the most severe hazards to soil ruins in humid regions, is often caused by a favorable hygrothermal environment, that is, high relative air humidity (RH) with a suitable temperature and other environmental variables. It was reported that no mold growth occurs in buildings when RH is less than 70%, and mold grows more easily and quickly as humidity increases (Sedlbauer, 2001). The characteristics of mold growth under extremely high humidity conditions remain elusive. In our previous research, samples from the Wenzhou Qiaolou soil ruin were used to estimate the effects of ventilation and lighting modes on mold growth. On that basis, subsequent experiments and analysis were conducted to assess the relationship between mold growth, and RH and lighting modes. In the experiments, six sets of initially wet samples were placed in artificial lighting or dark conditions with different RH to evaluate the characteristics of mold growth under extremely high humidity conditions. We found that extremely high humidity with a condensation environment had a significantly inhibitory effect on mold growth compared with the humidity range (94%–99%) favorable for it. Observations with the microscope conducted to understand the moisture condition of the sample surface confirmed a possibility that the reduction or isolation of oxygen under very high RH conditions with condensation caused this result. This paper provides basic knowledge regarding the characteristics of mold growth in an extremely high humidity environment, and is practically useful for methods of inhibition of mold growth in a high-humidity environment.

BackgroundEnvironmental factors, including air pollution, can strongly impact on spatio-temporal patterns of infectious diseases outbreak. In this study, we aimed to investigate the association and correlation between ambient air pollutants and case fatality rate (CFR) of the novel coronavirus disease (COVID-19) in China.MethodsPublicly accessible data on COVID-19 average CFR were utilized in the data analysis. The ambient daily air pollutants including fine particulate matter (PM2.5), inhalable particles (PM10) and nitrogen dioxide (NO2) during the period from December 25, 2019 to March 5, 2020 were obtained from National Air Quality Real-time Publishing System of China. Ecological analysis was performed to explore the association and correlation between the cumulative average exposure of ambient air pollutants at different lag days (14 and 28 days) and average CFR in China outside Hubei and cities in Hubei province via model fitting.ResultsThe average case fatality rate was highest in Wuhan city (4.53%) and the cumulative average exposure of ambient PM2.5, PM10 and NO2 at lag 28 days was 55.8±12.1μg/m3, 66.8±9.2μg/m3, 20.7±4.4μg/m3, respectively in Hubei province during the study period. Ecological analysis showed that ambient PM2.5, PM10 and NO2 exposure at both lag 14 and 28 days was positively correlated with average CFR in China outside Hubei (province-level). For city-level analysis in Hubei, significant associations were only found between cumulative ambient NO2 exposure and average CFR(r=0.693 for Lag0-14, r=0.697 for Lag0-28, respectively) during the same period.ConclusionOur findings suggested ambient PM2.5, PM10 and NO2 exposure, especially at 28 lag days, positively associated with the case fatality rate of COVID-19 in China. These results could help provide guidance for identifying potential exposure window and preventing and controlling the epidemic.

Background Cancer stem cells (CSCs) have been proposed to be responsible for tumor recurrence and chemo-resistance. Previous studies suggested that miR-153 played essential roles in lung cancer. However, the molecular mechanism of miR-153 in regulating the stemness of non-small cell lung cancer (NSCLC) remains poorly understood. In this study, we investigated the role of miR-153 in regulation of the stemness of NSCLC. Methods The stemness property of lung stem cancer cells was detected by sphere formation assay, immunofluorescence, and Western blot. Luciferase reporter assay was performed to investigate the direct binding of miR-153 to the 3′-UTR of JAG1 mRNA. Animal study was conducted to evaluate the effect of miR-153 on tumor growth in vivo. The clinical relevance of miR-153 in NSCLC was evaluated by Rt-PCR and Kaplan-Meier analysis. Results MiR-153 expression was decreased in lung cancer tissues. Reduced miR-153 expression was associated with lung metastasis and poor overall survival of lung cancer patients. Jagged1, one of the ligands of Notch1, is targeted by miR-153 and inversely correlates with miR-153 in human lung samples. More importantly, we found that miR-153 inhibited stem cell-like phenotype and tumor growth of lung adenocarcinoma through inactivating the Jagged1/Notch1 axis. Conclusion MiR-153 suppresses the stem cell-like phenotypes and tumor growth of lung adenocarcinoma by targeting Jagged1 and provides a potential therapeutic target in lung cancer therapy.

Background: Indomethacin is one of the non-steroidal anti-inflammatory drugs (NSAIDs) , and it was considered to have chemosensitization effects on many cancers, however, the mechanism of its effect on chemotherapy is still unclear. In this study, using human lung cancer SPC-A-1 cells, we examined the effects of indomethacin sensitize s human lung cancer cells to cisplatin (DDP). Methods: Human lung cancer SPC-A-1 cells were inoculated subcutaneously into BALB/c-nu/nu mice, and all the transplanted nude mice were divided into a control group, a DDP group and a indomethacin combined with DDP group , after daily treatment for 4 weeks a ll the mice were sacrificed by cervical dislocation. Immunohisto-chemical staining was employed to determine the expression of PCNA of lung tumor cell in the tumor tissues, western blot was used to detect the expression of autophagy related protein LC3-II and P62 What’s more, the formation of antophagosomes was observed through transmission electron microscope. Results: Compared with the control group and DDP group, we can find that tumor growth is very slow in indomethacin combined with DDP group , and the tumor weight decreased significantly in combined group. H&E staining reveal s that tumor cell necrosis is more obvious in combined group . The immunohistochemical staining results indicated that the expression of PCNA was much lower in combined group . than that in control and DDP group s.More importantly, western blot results show that the expression of LC3-II was significantly up-regulated in combined group than that in control group and DDP group ( P < 0.05 ) , and the expression of p62 protein was significantly down-regulated in combined group ( P < 0.05 ). Moreover, transmission electron microscope results show that compared with the control group and DDP group, the number of antophagosomes increased significantly in combined group. Conclusions : Our findings suggested that indomethacin can enhance the chemo s ensitivity of lung cancer cells to DDP, and the underlying mechanism maybe associated with the activation of autophagy.

Calcium-dependent proteolytic calpains are implicated in a variety of physiological processes, as well as pathologies associated with calcium overload. However, the mechanism by which calpain is activated remains elusive since intracellular calcium levels under physiological conditions do not reach the high concentration range required to trigger calpain activation. From a candidate screening using the abundance of the calpain target glutamate receptor GluRIIA at the Drosophila neuromuscular junction as a readout, we uncovered that calpain activity was inhibited upon knockdown of Ttm50, a subunit of the Tim23 complex known to be involved in the import of proteins across the mitochondrial inner membrane. Unexpectedly, Ttm50 and calpain are co-localized at calcium stores Golgi and endoplasmic reticulum (ER), and Ttm50 interacts with calpain via its C-terminal domain. This interaction is required for calpain localization at Golgi/ER, and increases calcium sensitivity of calpain by roughly an order of magnitude. Our findings reveal the regulation of calpain activation by Ttm50, and shed new light on calpain-associated pathologies.

Two new flavonoids, pauciaurone A (1) and pauciisoflavone A (2), together with three known isoflavones (3–5), were isolated from the stems of Garcinia paucinervis. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were tested for their cytotoxicities against five human tumor cell lines and showed potential cytotoxic properties against certain tumor cell lines.

Investigation of an organic extract of the stems of Garcinia bracteata led to the isolation of two new flavones, named bracflavones A (1) and B (2). Their structures were elucidated by spectroscopic evidence. The compounds feature an isopropoxy group at C-3 compared with related known flavonoids isolated from the genus Garcinia. Compounds 1 and 2 were tested for their cytotoxicity. The results revealed that compound 1 showed high cytotoxicity against A549 and PC3 cell lines, and compound 2 showed high cytotoxicity against NB4, A549, SH-SY5Y, PC3, and MCF7 cell lines.

Calpains are calcium-dependent, cytosolic proteinases active at neutral pH. They do not degrade but cleave substrates at limited sites. Calpains are implicated in various pathologies, such as ischemia, injuries, muscular dystrophy, and neurodegeneration. Despite so, the physiological function of calpains remains to be clearly defined. Using the neuromuscular junction of Drosophila of both sexes as a model, we performed RNAi screening and uncovered that calpains negatively regulated protein levels of the glutamate receptor GluRIIA but not GluRIIB. We then showed that calpains enrich at the postsynaptic area, and the calcium-dependent activation of calpains induced cleavage of GluRIIA at Q788 of its C terminus. Further genetic and biochemical experiments revealed that different calpains genetically and physically interact to form a protein complex. The protein complex was required for the proteinase activation to downregulate GluRIIA. Our data provide a novel insight into the mechanisms by which different calpains act together as a complex to specifically control GluRIIA levels and consequently synaptic function. SIGNIFICANCE STATEMENT Calpain has been implicated in neural insults and neurodegeneration. However, the physiological function of calpains in the nervous system remains to be defined. Here, we show that calpain enriches at the postsynaptic area and negatively and specifically regulates GluRIIA, but not IIB, level during development. Calcium-dependent activation of calpain cleaves GluRIIA at Q788 of its C terminus. Different calpains constitute an active protease complex to cleave its target. This study reveals a critical role of calpains during development to specifically cleave GluRIIA at synapses and consequently regulate synaptic function.

The kinetochore is a complex of proteins, broadly conserved from yeast to man, that resides at the centromere and is essential for chromosome segregation in dividing cells. There are no known functions of the core complex outside of the centromere. We now show that the proteins of the kinetochore have an essential post-mitotic function in neurodevelopment. At the embryonic neuromuscular junction of Drosophila melanogaster, mutation or knockdown of many kinetochore components cause neurites to overgrow and prevent formation of normal synaptic boutons. Kinetochore proteins were detected in synapses and axons in Drosophila. In post-mitotic cultured hippocampal neurons, knockdown of mis12 increased the filopodia-like protrusions in this region. We conclude that the proteins of the kinetochore are repurposed to sculpt developing synapses and dendrites and thereby contribute to the correct development of neuronal circuits in both invertebrates and mammals.

Optical emission spectroscopy measurements of dual-frequency capacitively coupled CF4 plasmas were carried out. The gas temperature (Tg) was acquired by fitting the optical emission spectra of a CF B—X system in 201~206 nm. The atomic fluorine concentration and the electron temperature (Te) were obtained by trace rare gas optical emission spectroscopy and a modified Boltzmann plot technique, respectively. It was found that the gas temperature was about 620±30 K at 50 mTorr and the atomic fluorine concentration increased while the electron temperature decreased with increasing gas pressure and power of high frequency (60 MHz). With increasing low frequency (2 MHz) power, the electron temperature also increased, but the atomic fluorine concentration was insensitive to this change. The generation and disappearance mechanisms of F atoms are discussed.

This paper studies the three-dimensional elastic formation control problem of multiple unmanned aerial vehicles (Multi-UAVs). To make the formation geometric shapes adapt to the flight velocity, three-dimensional elastic distance vector are proposed. The terminal formation shapes can be set with the vector about desired look-ahead point. On this basis, the follower vehicles' motion equations are put forward. Moreover, the formation reconfiguration is modeled as a fuel optimal control problem, which is transformed into a nonlinear programming problem by Chebyshev pseudospectral method. Numerical simulations indicate the proposed elastic formation reconfiguration algorithm is effective, robust and flexible.

For a team of unmanned aerial vehicles (UAVs) in leader-follower mode, the dynamic relative position relationships between follower vehicles and leader vehicle are described with elastic distance vector. The desired geometric shape in formation reconfiguration is constructed via the elastic coefficient matrix of distance. So the second-order kinematics model, follower vehicles' control equation is linearized with the elastic distance vector. Furthermore, the problem of formation flying reconfiguration is described as a time-optimal control problem with constrains. Pseudospectral Legendre method is proposed to find this time-optimal solution. Simulation results show that this control method can solve the formation flight reconfiguration effectively. Moreover, the elastic distance between two adjacent vehicles can adapt to the changes of the follower vehicles' velocities, so the tracking performance is improved greatly and become more secure.

Local measurement of plasma radial uniformity was performed in a dual frequency capacitively coupled argon plasma (DF-CCP) reactor using an optical probe. The optical probe collects the light emission from a small separate volume in plasma, thus enabling to diagnose the plasma uniformity for different experimental parameters. Both the gas pressure and the low-frequency (LF) power have apparent effects on the radial uniformity of argon plasma. With the increase in either pressure or LF power, the emission profiles changed from a bell-shaped to a double-peak distribution. The influence of a fused-silica ring around the electrodes on the plasma uniformity was also studied using the optical probe. Possible reasons that result in nonuniform plasmas in our experiments are discussed.

Radial non-uniformities of dual frequency capacitively coupled argon plasma were experimentally studied, using an optical emission spectroscopy probe, for different discharge pressures, discharge gaps, and frequencies and powers of the low frequency source. It was shown that the plasma emission profiles strongly depend on the working gas pressure and the lower frequency (LF) power. With the increasing LF power the emission profiles changed from a bell-shaped distribution at low LF power to a double-peak distribution at high LF power.

The syntheses of three carbazyl-containing quinacridone derivatives, N,N′-di((N-carbazyl)-n-butyl) quinacridone (DCBQA), N,N′-di((N-carbazyl)-n-hexyl)quinacridone (DCHQA) and N,N′-di((N-carbazyl)-n-octyl)quinacridone (DCOQA), are reported, and the photoluminescent (PL) characteristics are presented. The single crystal X-ray structures of DCBQA, DCHQA and DCOQA are investigated. The crystal of DCBQA is characterized by intermolecular п•••п interactions between quinacridone cores and carbazole moieties resulting in the formation of DCBQA molecule layer, in which every quinacridone core is surrounded by four carbazole groups. In DCHQA crystal, molecules assemble into two kinds of oriented columns based on intermolecular п•••п interactions between quinacridone cores. The DCOQA crystal displays intermolecular CH•••п and hydrogen bonding interactions feature. In DCOQA solid, every quinacridone core is sandwiched by two alkyl chains from two adjacent DCOQA molecules and simultaneously linked together with two other quinacridone cores by hydrogen bonding interactions. The PL spectra of the three compounds in solution exhibit concentration-dependent properties and their PL quantum causes decrease with the increasing concentration.

The hydroxyl radical (OH) plays an important role in combustion systems, atmospheric chemistry and the removal of air pollutants by non-thermal plasmas. The present work reports the determination of the hydroxyl radicals in atmospheric dielectric barrier discharge plasmas via near infrared continuous wave cavity ring-down spectroscopy. The P-branches of OH X2Πi (ν' = 2 ←ν′′ = 0) bands were used for its number density measurements. The minimum measurable absorption coefficient is about 3 × 10-8 cm-1 in DBD plasmas. At certain experimental conditions (a.c. frequency of 70 kHz, 6700 ppm H2O in He, 1 atm), when the peak-to-peak discharge voltage varied from 6 kV to 10.4 kV, the determined OH radical concentration increased from (2.1 ± 0.1) × 1013 molecules cm-3 to (3.7 ± 0.1) × 1013 molecules cm-3. The plasma gas temperature, derived from the Boltzmann plots of OH rotational population distributions, ranged from 312 ± 10 K to 363 ± 10 K when the discharge voltage was raised in the above range. The influences of O2 and N2 addition on the production of OH radicals have been also investigated.

Altered expression of the E3 ubiquitin ligase UBE3A, which is involved in protein degradation through the proteasome-mediated pathway, is associated with neurodevelopmental and behavioral defects observed in Angelman syndrome (AS) and autism. However, little is known about the neuronal function of UBE3A and the pathogenesis of UBE3A-associated disorders. To understand the in vivo function of UBE3A in the nervous system, we generated multiple mutations of ube3a, the Drosophila ortholog of UBE3A. We found a significantly increased number of total boutons and satellite boutons in conjunction with compromised endocytosis in the neuromuscular junctions (NMJs) of ube3a mutants compared to the wild type. Genetic and biochemical analysis showed upregulation of bone morphogenetic protein (BMP) signaling in the nervous system of ube3a mutants. An immunochemical study revealed a specific increase in the protein level of Thickveins (Tkv), a type I BMP receptor, but not other BMP receptors Wishful thinking (Wit) and Saxophone (Sax), in ube3a mutants. Ube3a was associated with and specifically ubiquitinated lysine 227 within the cytoplasmic tail of Tkv, and promoted its proteasomal degradation in Schneider 2 cells. Negative regulation of Tkv by Ube3a was conserved in mammalian cells. These results reveal a critical role for Ube3a in regulating NMJ synapse development by repressing BMP signaling. This study sheds new light onto the neuronal functions of UBE3A and provides novel perspectives for understanding the pathogenesis of UBE3A-associated disorders., Author Summary Angelman syndrome (AS), characterized by severe mental retardation, developmental delay, ataxia, seizures, speech impairment, and happy disposition, is caused by mutation of E3 ubiquitin ligase UBE3A; a critical enzyme involved in proteasome-mediated protein degradation. Increasing evidence demonstrates that overexpression or hyperactivation of UBE3A is associated with autism. Thus, both loss and gain of UBE3A functions result in neurodevelopmental and cognitive defects. However, the neuronal functions of UBE3A and the mechanism by which altered expression of UBE3A leads to developmental and cognitive defects are poorly understood. Using Drosophila melanogaster as a model system in conjunction with an array of biochemical and physiological assays, we showed that mutants of ube3a had excess synaptic boutons and endocytic defects at the neuromuscular junction terminals due to an elevated level of bone morphogenetic protein (BMP) signaling. Specifically, Ube3a directly binds and ubiquitinates the BMP receptor Thickveins for proteasomal degradation; a function that is conserved in mammalian cells. Negative regulation of BMP signaling by UBE3A suggests a previously unknown molecular mechanism that underlies the pathogenesis of UBE3A-associated AS and autism.

Synaptic connections must be precisely controlled to ensure proper neural circuit formation. In Drosophila melanogaster, bone morphogenetic protein (BMP) promotes growth of the neuromuscular junction (NMJ) by binding and activating the BMP ligand receptors wishful thinking (Wit) and thickveins (Tkv) expressed in motor neurons. We report here that an evolutionally conserved, previously uncharacterized member of the S6 kinase (S6K) family S6K like (S6KL) acts as a negative regulator of BMP signaling. S6KL null mutants were viable and fertile but exhibited more satellite boutons, fewer and larger synaptic vesicles, larger spontaneous miniature excitatory junctional potential (mEJP) amplitudes, and reduced synaptic endocytosis at the NMJ terminals. Reducing the gene dose by half of tkv in S6KL mutant background reversed the NMJ overgrowth phenotype. The NMJ phenotypes of S6KL mutants were accompanied by an elevated level of Tkv protein and phosphorylated Mad, an effector of the BMP signaling pathway, in the nervous system. In addition, Tkv physically interacted with S6KL in cultured S2 cells. Furthermore, knockdown of S6KL enhanced Tkv expression, while S6KL overexpression downregulated Tkv in cultured S2 cells. This latter effect was blocked by the proteasome inhibitor MG132. Our results together demonstrate for the first time that S6KL regulates synaptic development and function by facilitating proteasomal degradation of the BMP receptor Tkv., Author Summary Bi-directional signaling between neurons and their target cells is critical for synapse formation, growth, and plasticity, as well as for neuronal survival. Bone morphogenetic protein (BMP) acts as a retrograde signal promoting synaptic growth at the Drosophila neuromuscular junction (NMJ), but little is known about proteins that regulate BMP signaling by controlling BMP release, receptor expression, and signal transduction. We report here that a previously uncharacterized and evolutionally conserved member of the S6 kinase (S6K) family S6K like (S6KL) inhibits BMP signaling by interacting with and promoting proteasome-mediated degradation of the BMP receptor Thickveins (Tkv). In S6KL mutants, there was an elevated level of Tkv protein, together with overgrown NMJs characterized by excess satellite boutons. Reducing the gene dose of tkv by half in S6KL null background restored normal NMJ morphology, suggesting that S6KL normally serves to suppress Tkv-mediated BMP signaling. Biochemically, S6KL interacted with Tkv. Overexpression of S6KL down-regulated Tkv and this effect was inhibited by blocking the proteasomal degradation pathway. Collectively, our data demonstrate that S6KL regulates NMJ synapse development by promoting the proteasomal degradation of Tkv. Thus, we have identified a novel negative regulator of BMP signaling in the Drosophila nervous system.

Two new xanthones, bracthone A (Ia) and B (Ib), are isolated from the stems of Garcinia bracteata together with four known xanthones.

The nanos gene encodes a zinc-finger protein which is required for the migration and differentiation of primordial germ cells as well as for their fate maintenance. In this study, a 1913 bp nanos gene was cloned and characterized in silkworm (Bombyx mori). RT-PCR and Western blot analysis showed that the nanos was expressed in developing embryos and various silkworm larval tissues. The expression patterns of Nanos and Vasa in silkworm larval gonads were analyzed using immunohistochemistry. It was found that, in silkworm larval ovaries, the Nanos and Vasa proteins were expressed in oocytes. While in testes, high expression of Nanos and Vasa was detected in spermatogonia and relatively weaker expression was found in spermatocytes at latter stages.

Gene nanos is a maternal posterior group gene required for normal development of abdominal segments and the germ line in Drosophila. Expression of nanos-related genes is associated with the germ line in a broad variety of other taxa. In this study, the 5'-RACE method and the in silico cloning method are used to isolate the new nanos-like gene of Bombyx mori and the gene obtained is analyzed with bioinformatics tools. The putative protein is expressed in Escherichia coli and the antiserum has been produced in New Zealand white rabbits. The result shows that the nanos cDNA is 1,913 bp in full length and contains a 954 bp open reading frame. The deduced protein has 317 amino acid residues, with a predicted molecular weight of 35 kDa, isoelectric point of 5. 38, and contains a conserved nanos RNA binding domain. The conserved region of the deduced protein shares 73% homology with the nanos protein conserved region of Honeybee (Apis mellifera). This gene has been registered in the GenBank under the accession number EF647589. One encoding sequence of the nanos fragment has been successfully expressed in E. coli. Western blotting analysis indicates that homemade antiserum can specifically detect nanos protein expressed in prokaryotic cells.

Based upon research on sound and vibration characteristics of tool condition, we explore the multigrade monitoring system which takes single-chip microcomputers as the core hardware. By using the specially designed pickup true signal devices, we can more effectively do the intelligent multigrade monitoring and forecasting, and furthermore, we can build the tool condition models adaptively. This is the key problem in FMS, CIMS, and even the IMS.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The hydroperoxyl radical (HO2) plays an important role in combustion systems, atmospheric chemistry and the removal of air pollutants by non-thermal plasmas. This work reports the determination of the hydroperoxyl radical in dielectric barrier discharge plasmas via near-infrared continuous wave cavity ring-down spectroscopy. HO2 radicals were observed in discharges of HCHO/O2/H2O/N2 mixtures around 6625.7 cm−1 in the first H–OO stretching overtone, (2, 0, 0)–(0, 0, 0), of its ground electronic state . At certain discharge conditions (ac frequency of 5 kHz, peak-to-peak voltage of 6.5 kV, 1900 ppm HCHO, 20% O2, 3.5% H2O in N2, Ptotal = 30 Torr), HO2 radical concentration was determined to be 1.0 × 1013 molecules cm−3. The temporary evolution of HO2 concentration was obtained using the 'time window' method. The effects of oxygen concentration, water concentration, the discharge voltage and discharge gas pressure on the concentration of HO2 radicals have been investigated. The detection limit of our setup for the HO2 radical is ~1 × 1011 molecules cm−3.

The vacuolar ATPase (V-ATPase) is a multifunctional enzyme that consists of several subunits. Subunit B is a part of the catalytic domain of the enzyme. The result of the RTPCR suggested that the V-ATPase B subunit is a ubiquitous gene. 24 h after the larvae were infected with the Bombyx mori nucleopolyhedrovirus (BmNPV), the expression level of the V-ATPase B subunit in the midgut of the resistant strain NB was about 3 times higher than in the susceptible strain 306, and then the expression level of the V-ATPase B subunit decreased rapidly to a very low level. This indicated that the virus may cause a lot of changes of physiological conditions in the midgut. Localization of the V-ATPase B subunit was attempted in midgut cells of Bombyx mori by immunohistochemistry. The immunohistochemical localization with the antibody against the B subunit revealed a positive staining in goblet cell apical membranes of Bombyx mori midgut cells as well as in the midgut of Manduca sexta. This sequence has been registered in GenBank under the accession number EU727173.