Nonmuscle Myosin II helps regulate synaptic vesicle mobility at the Drosophila neuromuscular junction

<p>Abstract</p> <p>Background</p> <p>Although the mechanistic details of the vesicle transport process from the cell body to the nerve terminal are well described, the mechanisms underlying vesicle traffic within nerve terminal boutons is relatively unknown. The actin cytoskeleton has been implicated but exactly how actin or actin-binding proteins participate in vesicle movement is not clear.</p> <p>Results</p> <p>In the present study we have identified Nonmuscle Myosin II as a candidate molecule important for synaptic vesicle traffic within <it>Drosophila </it>larval neuromuscular boutons. Nonmuscle Myosin II was found to be localized at the <it>Drosophila </it>larval neuromuscular junction; genetics and pharmacology combined with the time-lapse imaging technique FRAP were used to reveal a contribution of Nonmuscle Myosin II to synaptic vesicle movement. FRAP analysis showed that vesicle dynamics were highly dependent on the expression level of Nonmuscle Myosin II.</p> <p>Conclusion</p> <p>Our results provide evidence that Nonmuscle Myosin II is present presynaptically, is important for synaptic vesicle mobility and suggests a role for Nonmuscle Myosin II in shuttling vesicles at the <it>Drosophila </it>neuromuscular junction. This work begins to reveal the process by which synaptic vesicles traverse within the bouton.</p

Surface and Subsurface Characteristics Related to Abrasive-Planing Conditions

The goal of this study was to examine the quality of abrasively planed wood surfaces when variable grit sizes, feed speeds, and depths of cut are used. Our observations show that grit size and wood structure and density seem to have larger effects on the depth and type of damage than feed speed and depth of cut. Coarser grit sizes seem to cause greater damage than finer grit sizes.Surface damage in Douglas-fir occurs at every grit size, feed rate, and depth of cut combination; the earlywood shows more severe damage than the latewood. Surface damage is more variable in hard maple and yellow-poplar than in Douglas-fir. This variability may be due to different cell types present at the surface and the angle of intersection between the surface and the rays. Similar machining conditions do not always have similar effects on the surface quality even in the same wood species. Other factors, such as moisture content, between and within species density variations or belt conditions, might also contribute to the surface quality variability, but these were not explored

Myosin VI contributes to synaptic transmission and development at the Drosophila neuromuscular junction

Abstract Background Myosin VI, encoded by jaguar (jar) in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins. Myosin VI is the only myosin known to move towards the minus or pointed ends of actin filaments. Although Myosin VI has been implicated in numerous cellular processes as both an anchor and a transporter, little is known about the role of Myosin VI in the nervous system. We previously recovered jar in a screen for genes that modify neuromuscular junction (NMJ) development and here we report on the genetic analysis of Myosin VI in synaptic development and function using loss of function jar alleles. Results Our experiments on Drosophila third instar larvae revealed decreased locomotor activity, a decrease in NMJ length, a reduction in synaptic bouton number, and altered synaptic vesicle localization in jar mutants. Furthermore, our studies of synaptic transmission revealed alterations in both basal synaptic transmission and short-term plasticity at the jar mutant neuromuscular synapse. Conclusions Altogether these findings indicate that Myosin VI is important for proper synaptic function and morphology. Myosin VI may be functioning as an anchor to tether vesicles to the bouton periphery and, thereby, participating in the regulation of synaptic vesicle mobilization during synaptic transmission

Environmental and genetic factors associated with Solanesol accumulation in potato leaves

Solanesol is a high value 45-carbon, unsaturated, all-trans-nonaprenol isoprenoid. Recently solanesol has received particular attention because of its utility, both in its own right and as a precursor in the production of numerous compounds used in the treatment of disease states. Solanesol is found mainly in solanaceous crops such as potato, tomato, tobacco and pepper where it accumulates in the foliage. There is considerable potential to explore the extraction of solanesol from these sources as a valuable co-product. In this study we have characterised the genetic variation in leaf solanesol content in a biparental, segregating diploid potato population. We demonstrate that potato leaf solanesol content is genetically controlled and identify several quantitative trait loci associated with leaf solanesol content. Transient over-expression of genes from the methylerythritol 4-phosphate (MEP) and mevalonic acid (MVA) pathways, either singly or in combination, resulted in enhanced accumulation of solanesol in leaves of Nicotiana benthamiana, providing insights for genetically engineering the pathway. We also demonstrate that in potato, leaf solanesol content is enhanced by up to six-fold on exposure to moderately elevated temperature and show corresponding changes in expression patterns of MEP and MVA genes. Our combined approaches offer new insights into solanesol accumulation and strategies for developing a bio-refinery approach to potato production

The use of stained cytologic direct smears for ALK gene rearrangement analysis of lung adenocarcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100150/1/cncy21286.pd

Reducing Risk for Illicit Drug Use and Prescription Drug Misuse: High School Gay-Straight Alliances and Lesbian, Gay, Bisexual, and Transgender Youth

Previous research suggests that lesbian, gay, bisexual, and transgender (LGBT) youth are at elevated risk for using illicit drugs and misusing prescription drugs relative to heterosexual youth. Previous research also indicates that LGBT youth who attend high schools with a gay-straight alliance (GSA) report having fewer alcohol problems and lower levels of cigarette smoking. The present study investigates whether the absence of a GSA is associated with risk for illicit drug use and prescription drug misuse in a sample of 475 LGBT high school students (M age = 16.79) who completed an online survey. After controlling for demographic variables and risk factors associated with illicit drug use, the results of 12 logistic regression analyses revealed that LGBT youth attending a high school without a GSA evidenced increased risk for using cocaine (adjusted odds ratio [adjOR] = 3.11; 95% confidence interval [95% CI] = 1.23–7.86), hallucinogens (adjOR = 2.59; 95% CI = 1.18–5.70), and marijuana (adjOR = 2.22; 95% CI = 1.37–3.59) relative to peers attending a high school with a GSA. Youth without a GSA also evidenced increased risk for the misuse of ADHD medication (adjOR = 2.00; 95% CI = 1.02–3.92) and prescription pain medication (adjOR = 2.00; 95% CI = 1.10–3.65). These findings extend the research base related to GSAs and further demonstrate the importance of providing LGBT youth with opportunities for socialization and support within the school setting. Important limitations of the present study are reviewed

Bailing Out the Milky Way: Variation in the Properties of Massive Dwarfs Among Galaxy-Sized Systems

Recent kinematical constraints on the internal densities of the Milky Way's dwarf satellites have revealed a discrepancy with the subhalo populations of simulated Galaxy-scale halos in the standard CDM model of hierarchical structure formation. This has been dubbed the "too big to fail" problem, with reference to the improbability of large and invisible companions existing in the Galactic environment. In this paper, we argue that both the Milky Way observations and simulated subhalos are consistent with the predictions of the standard model for structure formation. Specifically, we show that there is significant variation in the properties of subhalos among distinct host halos of fixed mass and suggest that this can reasonably account for the deficit of dense satellites in the Milky Way. We exploit well-tested analytic techniques to predict the properties in a large sample of distinct host halos with a variety of masses spanning the range expected of the Galactic halo. The analytic model produces subhalo populations consistent with both Via Lactea II and Aquarius, and our results suggest that natural variation in subhalo properties suffices to explain the discrepancy between Milky Way satellite kinematics and these numerical simulations. At least ~10% of Milky Way-sized halos host subhalo populations for which there is no "too big to fail" problem, even when the host halo mass is as large as M_host = 10^12.2 h^-1 M_sun. Follow-up studies consisting of high-resolution simulations of a large number of Milky Way-sized hosts are necessary to confirm our predictions. In the absence of such efforts, the "too big to fail" problem does not appear to be a significant challenge to the standard model of hierarchical formation. [abridged]Comment: 12 pages, 3 figures; accepted by JCAP. Replaced with published versio

Diesel Exhaust Exposure and Cause-Specific Mortality in the Diesel Exhaust in Miners Study II (DEMS II) Cohort

BACKGROUND: With the exception of lung cancer, the health effects associated with diesel exhaust for other cancers and nonmalignant health outcomes are not well understood. OBJECTIVES: We extended the mortality follow-up of the Diesel Exhaust in Miners Study, a cohort study of 12,315 workers, by 18 y (ending 31 December 2015), more than doubling the number of observed deaths to n = 4,887, to evaluate associations between mortality and diesel exhaust exposure. METHODS: Quantitative estimates of historical exposure to respirable elemental carbon (REC), a surrogate for diesel exhaust, were created for all jobs, by year and facility, using measurements collected from each mine, as well as historical measurements. Standardized mortality ratios (SMRs) and hazard ratios (HRs) were estimated for the entire cohort and by worker location (surface, underground). RESULTS: We observed an excess of death for cancers of the lung, trachea, and bronchus (n = 409; SMR = 1:24; 95% CI: 1.13, 1.37). Among workers who ever worked underground, where the majority of diesel exposure occurred, excess deaths were evident for lung, trachea, and bronchus cancers (n = 266; SMR = 1:26; 95% CI: 1.11, 1.42). Several nonmalignant diseases were associated with excess mortality among workers ever-employed underground, including ischemic heart disease (SMR = 1:08; 95% CI: 1.00, 1.16), cerebrovascular disease (SMR = 1:22; 95% CI: 1.04, 1.43), and nonmalignant diseases of the respiratory system (SMR = 1:13; 95% CI: 1.01, 1.26). Continuous 15-y lagged cumulative REC exposure <1,280 lg/m3-y was associated with increased lung cancer risk (HR = 1:93; 95% CI: 1.24, 3.03), but the risk declined at the highest exposures (HR = 1:29; 95% CI: 0.74, 2.26). We also observed a significant trend in non-Hodgkin lymphoma (NHL) risk with increasing 20-y lagged cumulative REC (HRTertile3 vs: Tertile1 = 3:12; 95% CI: 1.00, 9.79; p-trend = 0:031). DISCUSSION: Increased risks of lung cancer mortality observed in the original study were sustained. Observed associations between diesel exposure and risk of death from NHL and the excesses in deaths for diseases of the respiratory and cardiovascular system, including ischemic heart disease and cerebrovascular disease, warrant further study and provide evidence of the potential widespread public health impact of diesel exposure