Pathways for fatty acid elongation and desaturation in Neurospora crassa

Neurospora crassa incorporated exogenous deuterated palmitate (16∶0) and ¹⁴C-labeled oleate (18∶1^Δ9) into cell lipids. Of the exogenous 18∶1^Δ9 incorporated, 59% was desaturated to 18∶2^Δ9,12 and 18∶3^Δ9,12,15. Of the exogenous 16∶0 incorporated, 20% was elongated to 18∶0, while 37% was elongated and desaturated into 18∶1^Δ9, 18∶2^Δ9,12, and 18∶3^Δ9,12,15. The mass of unsaturated fatty acids in phospholipid and triacylglycerol is 12 times greater than the mass of 18∶0. Deuterium label incorporation in unsaturated fatty acids is only twofold greater than in 18∶0, indicating a sixfold preferential use of 16∶0 for saturated fatty acid synthesis. These results indicate that the release of 16∶0 from fatty acid synthase is a key control point that influences fatty acid composition in Neurospora.     

Application of a glyphosate-based herbicide to Phragmites australis: Impact on groundwater and near-shore lake water at a beach on Georgian Bay

During the past decade, the invasive Phragmites australis (common reed) has established itself along beaches of the Great Lakes, causing detrimental impacts to both the natural ecological integrity of the shoreline and the recreational value of beaches. The herbicide Roundup®, containing the active ingredient glyphosate, was applied to Phragmites along a beach on the southern shore of Georgian Bay, Canada, to eradicate the Phragmites which was destroying the natural beach ecosystem. Groundwater and lake water were tested to determine if glyphosate enters the groundwater and lake at the beach and how long glyphosate will persist. Two days after application, the geometric mean concentration of glyphosate in the groundwater below the Phragmites was 0.060 μg/L with a maximum of 12.50 μg/L. Concentrations rapidly declined over the next two to three weeks to below minimum detection limits (< 0.020 μg/L). Glyphosate was also detected in the nearshore lake water with concentrations peaking at a geometric mean of 0.14 μg/L one week after application, and declining to 0.039 μg/L four weeks after application. Concentrations of glyphosate never exceeded the Canadian water quality guideline for the protection of aquatic life (65 μg/L) in either the groundwater or lake water. An approximate half-life for the dissipation of glyphosate by degradation and dilution/flushing as groundwater flows toward the lake, assuming a first order kinetic reaction, yielded a half-life of 3.5 during the 4 weeks after the herbicide was applied. The application of Roundup® resulted in an 90% reduction in the size of the stand of Phragmites.     

Application of the Soil and Water Assessment Tool for six watersheds of Lake Erie: Model parameterization and calibration

The Soil and Water Assessment Tool (SWAT), a physically-based watershed-scale model, holds promise as a means to predict tributary sediment and nutrient loads to the Laurentian Great Lakes. In the present study, model performance is compared across six watersheds draining into Lake Erie to determine the applicability of SWAT to watersheds of differing characteristics. After initial model parameterization, the Huron, Raisin, Maumee, Sandusky, Cuyahoga, and Grand SWAT models were calibrated (1998-2001) and confirmed, or validated (2002-2005), individually for stream water discharge, sediment loads, and nutrient loads (total P, soluble reactive P, total N, and nitrate) based on available datasets. SWAT effectively predicted hydrology and sediments across a range of watershed characteristics. SWAT estimation of nutrient loads was weaker although still satisfactory at least two-thirds of the time across all nutrient parameters and watersheds. SWAT model performance was most satisfactory in agricultural and forested watersheds, and was less so in urbanized settings. Model performance was influenced by the availability of observational data with high sampling frequency and long duration for calibration and confirmation evaluation. In some instances, it appeared that parameter adjustments that improved calibration of hydrology negatively affected subsequent sediment and nutrient calibration, suggesting trade-offs in calibrating for hydrologic vs. water quality model performance. Despite these considerations, SWAT accurately predicted average stream discharge, sediment loads, and nutrient loads for the Raisin, Maumee, Sandusky, and Grand watersheds such that future use of these SWAT models for various scenario testing is reasonable and warranted.     

Redox proteomics identification of 4‐hydroxynonenal‐modified brain proteins in Alzheimer's disease: Role of lipid peroxidation in Alzheimer's disease pathogenesis

Numerous studies have shown that neuronal lipids are highly susceptible to oxidative stress including in those brain areas directly involved in the neurodegenerative process of Alzheimer's disease (AD). Lipid peroxidation directly damages membranes and also generates a number of secondary biologically active products (toxic aldehydes)that are capable of easily attacking lipids, proteins, and DNA. Accumulating evidence has demonstrated regionally increased brain lipid peroxidation in patients with AD; however, extensive studies on specific targets of lipid peroxidation‐induced damage are still missing. The present study represents a further step in understanding the relationship between oxidative modification of protein and neuronal death associated with AD. We used a proteomics approach to determine specific targets of lipid peroxidation in AD brain, both in hippocampus and inferior parietal lobule, by coupling immunochemical detection of 4‐hydroxynonenal‐bound proteins with 2‐D polyacrylamide gel electrophoresis and MS analysis. We identified 4‐hydroxynonenal‐bound proteins in the hippocampus and inferior parietal lobule brain regions of subjects with AD. The identified proteins play different biological functions including energy metabolism, antioxidant system, and structural proteins, thus impairing multiple molecular pathways. Our results provide further evidence for the role of lipid peroxidation in the pathogenesis of AD.     

The effect of time of day on injury patterns amongst adolescents in Australia

Labour force participation of adolescents in Australia is growing at an unprecedented rate. This increased participation is coupled with a growing realisation of the vulnerability of adolescents in the labour market in terms of occupational injury. Despite recent evidence that time of day may be an important determinant of adolescent injuries, the impact of non-standard and night work on adolescent injury rates has received scant attention to date. The current study addresses this shortcoming by examining injury patterns of 3201 working adolescents in Queensland. Results revealed that female adolescents are 2.5 times more likely to sustain an injury on day shift and 4.71 times more likely to sustain an injury on night shift than their adult counterparts when total work hours are taken into consideration. Similar results were found for male adolescents with an injury to work hours ratio of 2.19 on day shift and 3.05 on night shift. These findings point to the value of considering the temporal pattern of adolescent work in future research aimed at minimising injuries at work and improving the work experience of tomorrow's workforce.     

Subjects presented at ASHP Midyear Clinical Meetings, 1967-90

The subject matter and trends of presentations made at ASHP Midyear Clinical Meetings (MCMs) were studied. A computerized database of information from MCM and Annual Meeting (AM) program and abstract books was created. The data were analyzed to determine the distribution of MCM presentations by subject and by author for the period 1967 to 1990, determine if there were differences in subjects covered between MCMs and AMs, explore the proposition that there has been duplication of material in MCM presentations, and evaluate the frequency with which MCM presentations have been published in ASHP journals. The total number of presentations made at MCMs from 1967 through 1990 was 8180, while the total for the AMs was 1547 for the two periods (1962-71 and 1985-90) studied. The most common keywords in titles were "pharmacy," "drug," "patient," "hospital," and "service." All International Pharmaceutical Abstracts subject categories and two other categories were represented; presentations in the institutional pharmacy practice category were the most frequent, while pharmacognosy-related presentations were least frequent. The overwhelming number of authors made only one presentation and were listed as the first author. The subjects of presentations were similar between AMs and MCMs. A tendency toward duplication of material was found. Of the 8180 MCM presentations, at least 1005 were published in an ASHP journal. Between 1967 and 1990, presentations at MCMs covered a wide range of subjects but were sometimes duplicative or not on the cutting edge.     

Real time flood disaster monitoring based on energy efficient ensemble clustering mechanism in wireless sensor network

In this article, energy efficient ensemble clustering method (EECM) with black widow optimization (EECM-BWO) algorithm is proposed for effective data transmission with the help of real time flood disaster monitoring wireless sensor network (WSN). Initially, unified scalable ensemble clustering algorithm based on ensemble generation and consensus function is proposed for selecting the optimal routing path among the node using BWO algorithm. Then, biologically inspired routing black widow spiders optimization algorithm is proposed to trade off the nodes energy level, self-organization, and self-configuration in the WSN. The simulation is performed using NS2 simulator for validating the performance of the proposed EECM-BWO method. Here, in node, low delay achieves 24.07%, 72.58%, 51.36%, 81.75%, 77.74%, high packet delivery ratio achieves 70.83%, 53.93%, 90.23%, 43.58%, 24.58%, low packet drop attains 77.93%, 72.76%, 61.56%, 51.87%, 34.35%, low energy consumption attains 75.9%, 52.94%, 65.81%, 58%, 41.2% compared with existing energy-efficient clustering approach consolidated game theory as well as dual-cluster-head mode for WSNs energy-aware clustering by cuckoo optimization approach (EECM-COA), energy-aware clustering-based routing using multi-path reliable transmission with routing and control board (EECM-RCB-MRT), adaptive repair algorithm with temporally ordered routing algorithms for flood control strategy (EECM-AR-TORA-FCS), passive multi-hop clustering algorithm (EECM-PMC), dynamic source routing protocol based on genetic algorithm-bacterial foraging optimization (DSR-GA-BFO).     

Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography

BACKGROUND: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding. METHODS: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons. RESULTS: Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48). CONCLUSIONS: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.     

Domain flexibility in retroviral proteases: structural implications for drug resistant mutations

Rigid body rotation of five domains and movements within their interfacial joints provide a rational context for understanding why HIV protease mutations that arise in drug resistant strains are often spatially removed from the drug or substrate binding sites. Domain motions associated with substrate binding in the retroviral HIV-1 and SIV proteases are identified and characterized. These motions are in addition to closure of the flaps and result from rotations of approximately 6-7 degrees at primarily hydrophobic interfaces. A crystal structure of unliganded SIV protease (incorporating the point mutation Ser 4 His to stabilize the protease against autolysis) was determined to 2.0 A resolution in a new space group, P3221. The structure is in the most "open" conformation of any retroviral protease so far examined, with six residues of the flaps disordered. Comparison of this and unliganded HIV structures, with their respective liganded structures by difference distance matrixes identifies five domains of the protease dimer that move as rigid bodies against one another: one terminal domain encompassing the N- and C-terminal beta sheet of the dimer, two core domains containing the catalytic aspartic acids, and two flap domains. The two core domains rotate toward each other on substrate binding, reshaping the binding pocket. We therefore show that, for enzymes, mutations at interdomain interfaces that favor the unliganded form of the target active site will increase the off-rate of the inhibitor, allowing the substrate greater access for catalysis. This offers a mechanism of resistance to competitive inhibitors, especially when the forward enzymatic reaction rate exceeds the rate of substrate dissociation.     

Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aortic regurgitation and normal left ventricular performance

BACKGROUND: Optimal criteria for valve replacement are unclear in asymptomatic/minimally symptomatic patients with aortic regurgitation (AR) and normal left ventricular (LV) performance at rest. Moreover, previous studies have not assessed the prognostic capacity of load-adjusted LV performance ("contractility") variables, which may be fundamentally related to clinical state. Therefore, 18 years ago, we set out to test prospectively the hypothesis that objective noninvasive measures of LV size and performance and, specifically, of load-adjusted variables, assessed at rest and during exercise (ex), could predict the development of currently accepted indications for operation for AR. METHODS AND RESULTS: Clinical variables and measures of LV size, performance, and end-systolic wall stress (ESS) were assessed annually in 104 patients by radionuclide cineangiography at rest and maximal ex and by echocardiography at rest; ESS was derived during ex. During an average 7.3-year follow-up among patients who had not been operated on, 39 of 104 patients either died suddenly (n = 4) or developed operable symptoms only (n = 22) or subnormal LV performance with or without symptoms (n = 13) (progression rate=6.2%/y). By multivariate Cox model analysis, change (delta) in LV ejection fraction (EF) from rest to ex, normalized for deltaESS from rest to ex (deltaLVEF-deltaESS index), was the strongest predictor of progression to any end point or to sudden cardiac death alone. Unadjusted deltaLVEF was almost as efficient. Symptom status modified prediction on the basis of the deltaLVEF-deltaESS index. The population tercile at highest risk by deltaLVEF-deltaESS progressed to end points at a rate of 13.3%/y, and the lowest-risk tercile progressed at 1.8%/y. CONCLUSIONS: Currently accepted symptom and LV performance indications for valve replacement, as well as sudden cardiac death, can be predicted in asymptomatic/minimally symptomatic patients with AR by load-adjusted deltaLVEF-deltaESS index, which includes data obtained during exercise.