Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

On the role of different Skyrme forces and surface corrections in exotic cluster-decay

We present cluster decay studies of $^{56}$Ni$^*$ formed in heavy-ion collisions using different Skyrme forces. Our study reveals that different Skyrme forces do not alter the transfer structure of fractional yields significantly. The cluster decay half-lives of different clusters lies within \pm 10% for PCM and \pm 15% for UFM.Comment: 13 pages,6 figures and 1 table; in press Pramana Journal of Physics (2010

Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors

MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UV–vis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UV–vis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate

DEPLOYING TECHNOLOGY ADVANCEMENTS FOR CHARACTERIZING THE VADOSE ZONE IN SINGLE-SHELL TANK WASTE MANAGEMENT AREAS

As much as one million gallons of waste is believed to have leaked from tanks, pipelines or other equipment in the single-shell tank farm waste management areas (WMAs) within the 200 East and West areas of the U.S. Department of Energy's Hanford Site near Richland, Washington. Although some contamination has reached groundwater, most contamination still resides in the vadose zone. The magnitude ofthis problem requires new approaches for soil characterization if we are to understand the nature and extent of the contamination and take action to protect the enviromnent. Because of the complexity and expense of drilling traditional boreholes in contaminated soil, direct push characterization using a hydraulic hammer has been extensively employed. Direct push probe holes <3-inch diameter have been pushed to a maximum depth of 240 feet below ground surface in 200 East area. Previously gross gamma and moisture logging of these narrow probe holes was perfonned to identify the location of cesium-137 ({sup 137}Cs) (which has limited mobility in Hanford soil) and moisture peaks. Recently a bismuth germinate detector has been deployed for detecting and quantifying the spectrum of cobalt-60 ({sup 60}Co) (a more mobile contaminant), which provides additional information. The direct push system is configured to allow the collection ofmultiple soil core samples throughout the depth ofthe probe hole. The direct push unit has been used to place individual electrodes at a variety of depths as the probe hole is being decommissioned. These deep electrodes enable the use of soil resistivity measurement methods between surface and deep electrodes as-well-as between sets of deep electrodes. Initial testing of surface-to-deep electrode resistivity measurements in WMA C demonstrated significant improvement in defining the three dimensional extent of a contamination plume. A multiple-electrode string is presently being developed to further enhance the resolution of resistivity data. The combined use of direct push logging/sampling and soil resistivity measurement allows more extensive characterization of the large tank farm WMAs with less cost and time commitment than required by traditional methods. An additional tool is in the laboratory testing stage to support these investigations. A beta detection tool is being evaluated to determine if it might be deployed with the direct push unit to identify technetium-99 ({sup 99}Tc) contamination. {sup 99}Tc is a mobile, long-lived contaminant that is the major risk driver from tank waste contamination. A screening tool to locate {sup 99}Tc contamination is anticipated to further increase the cost-effectiveness ofvadose zone characterization efforts

The pathogenic exon 1 HTT protein is produced by incomplete splicing in Huntington’s disease patients

We have previously shown that exon 1 of the huntingtin gene does not always splice to exon 2 resulting in the production of a small polyadenylated mRNA (HTTexon1) that encodes the highly pathogenic exon 1 HTT protein. The level of this read-through product is proportional to CAG repeat length and is present in all knock-in mouse models of Huntington’s disease (HD) with CAG lengths of 50 and above and in the YAC128 and BACHD mouse models, both of which express a copy of the human HTT gene. We have now developed specific protocols for the quantitative analysis of the transcript levels of HTTexon1 in human tissue and applied these to a series of fibroblast lines and post-mortem brain samples from individuals with either adult-onset or juvenile-onset HD. We found that the HTTexon1 mRNA is present in fibroblasts from juvenile HD patients and can also be readily detected in the sensory motor cortex, hippocampus and cerebellum of post-mortem brains from HD individuals, particularly in those with early onset disease. This finding will have important implications for strategies to lower mutant HTT levels in patients and the design of future therapeutics

Significant reductions in human visual gamma frequency by the gaba reuptake inhibitor tiagabine revealed by robust peak frequency estimation

The frequency of visual gamma oscillations is determined by both the neuronal excitation-inhibition balance and the time constants of GABAergic processes. The gamma peak frequency has been linked to sensory processing, cognitive function, cortical structure, and may have a genetic contribution. To disentangle the intricate relationship among these factors, accurate and reliable estimates of peak frequency are required. Here, a bootstrapping approach that provides estimates of peak frequency reliability, thereby increasing the robustness of the inferences made on this parameter was developed. The method using both simulated data and real data from two previous pharmacological MEG studies of visual gamma with alcohol and tiagabine was validated. In particular, the study by Muthukumaraswamy et al. [] (Neuropsychopharmacology 38(6):1105-1112), in which GABAergic enhancement by tiagabine had previously demonstrated a null effect on visual gamma oscillations, contrasting with strong evidence from both animal models and very recent human studies was re-evaluated. After improved peak frequency estimation and additional exclusion of unreliably measured data, it was found that the GABA reuptake inhibitor tiagabine did produce, as predicted, a marked decrease in visual gamma oscillation frequency. This result demonstrates the potential impact of objective approaches to data quality control, and provides additional translational evidence for the mechanisms of GABAergic transmission generating gamma oscillations in humans. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc

Evolutionary Reduction of the First Thoracic Limb in Butterflies

Members of the diverse butterfly families Nymphalidae (brush-footed butterflies) and Riodinidae (metalmarks) have reduced first thoracic limbs and only use two pairs of legs for walking. In order to address questions about the detailed morphology and evolutionary origins of these reduced limbs, the three thoracic limbs of 13 species of butterflies representing all six butterfly families were examined and measured, and ancestral limb sizes were reconstructed for males and females separately. Differences in limb size across butterflies involve changes in limb segment size rather than number of limb segments. Reduction of the first limb in both nymphalids and riodinids appears particularly extensive in the femur, but the evolution of these reduced limbs is suggested to be a convergent evolutionary event. Possible developmental differences as well as ecological factors driving the evolution of reduced limbs are discussed

A Spatial Cluster Analysis of Tractor Overturns in Kentucky from 1960 to 2002

Agricultural tractor overturns without rollover protective structures are the leading cause of farm fatalities in the United States. To our knowledge, no studies have incorporated the spatial scan statistic in identifying high-risk areas for tractor overturns. The aim of this study was to determine whether tractor overturns cluster in certain parts of Kentucky and identify factors associated with tractor overturns.A spatial statistical analysis using Kulldorff's spatial scan statistic was performed to identify county clusters at greatest risk for tractor overturns. A regression analysis was then performed to identify factors associated with tractor overturns.The spatial analysis revealed a cluster of higher than expected tractor overturns in four counties in northern Kentucky (RR = 2.55) and 10 counties in eastern Kentucky (RR = 1.97). Higher rates of tractor overturns were associated with steeper average percent slope of pasture land by county (p = 0.0002) and a greater percent of total tractors with less than 40 horsepower by county (p<0.0001).This study reveals that geographic hotspots of tractor overturns exist in Kentucky and identifies factors associated with overturns. This study provides policymakers a guide to targeted county-level interventions (e.g., roll-over protective structures promotion interventions) with the intention of reducing tractor overturns in the highest risk counties in Kentucky