40 research outputs found

    Legacy Hg–Cu contamination of active stream sediments

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    The purpose of this study is to evaluate the longitudinal trends of mercury (Hg) and copper (Cu) in active channel sediments downstream from the Gold Hill mining district in the Piedmont of North Carolina. Mining for gold (Au

    Demonstration of Binding of Neuronal Calcium Sensor-1 to the Ca(v)2.1 P/Q-Type Calcium Channel

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    [Image: see text] In neurons, entry of extracellular calcium (Ca(2+)) into synaptic terminals through Ca(v)2.1 (P/Q-type) Ca(2+) channels is the driving force for exocytosis of neurotransmitter-containing synaptic vesicles. This class of Ca(2+) channel is, therefore, pivotal during normal neurotransmission in higher organisms. In response to channel opening and Ca(2+) influx, specific Ca(2+)-binding proteins associate with cytoplasmic regulatory domains of the P/Q channel to modulate subsequent channel opening. Channel modulation in this way influences synaptic plasticity with consequences for higher-level processes such as learning and memory acquisition. The ubiquitous Ca(2+)-sensing protein calmodulin (CaM) regulates the activity of all types of mammalian voltage-gated Ca(2+) channels, including the P/Q class, by direct binding to specific regulatory motifs. More recently, experimental evidence has highlighted a role for additional Ca(2+)-binding proteins, particularly of the CaBP and NCS families in the regulation of P/Q channels. NCS-1 is a protein found from yeast to humans and that regulates a diverse number of cellular functions. Physiological and genetic evidence indicates that NCS-1 regulates P/Q channel activity, including calcium-dependent facilitation, although a direct physical association between the proteins has yet to be demonstrated. In this study, we aimed to determine if there is a direct interaction between NCS-1 and the C-terminal cytoplasmic tail of the Ca(v)2.1 α-subunit. Using distinct but complementary approaches, including in vitro binding of bacterially expressed recombinant proteins, fluorescence spectrophotometry, isothermal titration calorimetry, nuclear magnetic resonance, and expression of fluorescently tagged proteins in mammalian cells, we show direct binding and demonstrate that CaM can compete for it. We speculate about how NCS-1/Ca(v)2.1 association might add to the complexity of calcium channel regulation mediated by other known calcium-sensing proteins and how this might help to fine-tune neurotransmission in the mammalian central nervous system

    Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

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    Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation

    The short-time structural plasticity of dendritic spines is altered in a model of Rett syndrome

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    The maturation of excitatory transmission comes about through a developmental period in which dendritic spines are highly motile and their number, form and size are rapidly changing. Surprisingly, although these processes are crucial for the formation of cortical circuitry, little is known about possible alterations of these processes in brain disease. By means of acute in vivo 2-photon imaging we show that the dynamic properties of dendritic spines of layer V cortical neurons are deeply affected in a mouse model of Rett syndrome (RTT) at a time around P25 when the neuronal phenotype of the disease is still mild. Then, we show that 24h after a subcutaneous injection of IGF-1 spine dynamics is restored. Our study demonstrates that spine dynamics in RTT mice is severely impaired early during development and suggest that treatments for RTT should be started very early in order to reestablish a normal period of spine plasticity

    Cell Death Pathways: a Novel Therapeutic Approach for Neuroscientists

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    Use of mining-contaminated sediment tracers to investigate the timing and rates of historical flood plain sedimentation

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    Changes in land use practices following European settlement in the 1830s produced accelerated sedimentation on virtually all valley floors in the Blue River Watershed, Wisconsin. The contamination of sediments by Pb and Zn mining allowed us to calculate cross-valley rates of flood plain sedimentation for three time periods: the pre-mining period (1830-1900), the mining period (1900-1920), and the post-mining period (1920-1997). Most of the eight valley floors examined contained multiple presettlement surfaces. Significantly higher rates of sedimentation occurred on the lower flood plain surfaces, while the terraces were high enough to prevent sedimentation from most floods. Higher rates of sedimentation on the lower surfaces eventually reduced valley floor relief and, consequently, lateral differences in sedimentation rates. Tributaries and larger valleys downstream exhibited differences in the timing and rates of historical flood plain sedimentation. While rates of sedimentation were high during the pre-mining period in tributary valleys, the lower valleys were receiving little or no pre-mining alluvium. Little pre-mining alluvium was found in mid-basin reaches, suggesting that most of the pre-mining sedimentation was limited to headwater locations. During the mining period, lateral channel migration and the development of meander belts increased the conveyance capacity of tributary and mid-basin channels, which decreased overbank flooding and produced lower rates of sedimentation during the post-mining period. The meander belt channels also had an effect on the lower portion of the watershed by increasing flood magnitudes and the transport of sediment downstream, thereby shifting the locus of sedimentation from the tributaries to the larger, lower valleys. Sedimentation rates in the largest, most downstream site were an order of magnitude higher during the post-mining period than any of the sites upstream

    Storage of Mining-Related Zinc in Floodplain Sediments, Blue River, Wisconsin

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    This study investigates spatial patterns of sediment-associated zinc (Zn) storage in floodplain deposits and the potential reintroduction of these metal-contaminated sediments to the active channel by bank erosion. We estimate patterns of Zn mass storage by combining longitudinal trends in Zn concentrations with measurements of sediment mass storage in overbank and point-bar deposits. Overbank deposits are the largest contaminant sink, storing five times more Zn than the point-bar deposits. While Zn concentrations decrease downstream because of dilution effects, the total mass of tn stored in floodplains is greatest in both the upstream reaches and in the wider lower valleys where low channel gradients promote rapid sedimentation. Zn storage is low in middle reaches where steep, narrow valleys with high stream power favor sediment transport over deposition. Overall, more than half of the Zn released by mining remains stored in floodplain deposits within the watershed. The remobilization of Zn from storage is more likely in the upstream and mid-basin reaches where high stream power increases rates of lateral channel migration. Channels in the lower valley lack the stream power to migrate laterally and remobilize the large Zn mass stored in overbank sediments

    Legacy Hg-Cu Contamination of Active Stream Sediments in the Gold Hill Mining District, North Carolina

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    The purpose of this study is to evaluate the longitudinal trends of mercury (Hg) and copper (Cu) in active channel sediments downstream from the Gold Hill mining district in the Piedmont of North Carolina. Mining for gold (Au) and Cu from 1844 to 1915 released both Hg (associated with Au processing) and Cu in a 254 km2 watershed. Multiple linear regression is used to quantify spatial and geochemical trends in 93 active channel samples collected from contaminated main stem and background tributary sites. Simple two-parameter regression models combining the effects of both watershed-scale dispersal processes (distance downstream) and reach-scale sediment transport (percent sand) explain 85 percent of the variance in Hg and 90 percent of the variance in Cu in active channel sediments. Contamination trends in two different sediment media, low bar and higher elevation bench deposits, were effectively similar when local grain size influence was accounted for in the two-parameter models. Background geochemistry models explain 84 percent of the variance of Hg and Cu in uncontaminated tributary samples using parameters related to grain-size, secondary geochemical substrates, and mineral weathering sources. More than 45 percent of the variance of Hg and 20 percent of Cu in contaminated sediment can be explained by background parameters. Geochemical signatures differ between Hg and Cu in active channel sediments due to variations in mining inputs, background geochemistry, and present-day pollution sources

    Legacy sediment, lead, and zinc storage in channel and floodplain deposits of the Big River, Old Lead Belt Mining District, Missouri, USA

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    The Old Lead Belt of southeastern Missouri was one of the leading producers of Pb ore for more than a century (1869-1972). Large quantities of contaminated mine waste have been, and continue to be, supplied to local streams. This study assessed the magnitude and spatial distribution of mining-contaminated legacy sediment stored in channel and floodplain deposits of the Big River in the Ozark Highlands of southeastern Missouri. Although metal concentrations decline downstream from the mine sources, the channel and floodplain sediments are contaminated above background levels with Pb and Zn along its entire 171-km length below the mine sources. Mean concentrations in floodplain cores \u3e 2000 mg kg− 1 for Pb and \u3e 1000 mg kg− 1 for Zn extend 40-50 km downstream from the mining area in association with the supply of fine tailings particles that were easily dispersed downstream in the suspended load. Mean concentrations in channel bed and bar sediments ranging from 1400 to 1700 mg kg− 1 for Pb extend 30 km below the mines, while Zn concentrations of 1000-3000 mg kg− 1 extend 20 km downstream. Coarse dolomite fragments in the 2-16 mm channel sediment fraction provide significant storage of Pb and Zn, representing 13-20% of the bulk sediment storage mass in the channel and can contain concentrations of \u3e 4000 mg kg− 1 for Pb and \u3e 1000 mg kg− 1 for Zn. These coarse tailings have been transported a maximum distance of only about 30 km from the source over a period of 120 years for an average of about 250 m/y. About 37% of the Pb and 9% of the Zn that was originally released to the watershed in tailings wastes is still stored in the Big River. A total of ~ 157 million Mg of contaminated sediment is stored along the Big River, with 92% of it located in floodplain deposits that are typically contaminated to depths of 1.5-3.5 m. These contaminated sediments store a total of 188,549 Mg of Pb and 34,299 Mg of Zn, of which 98% of the Pb and 95% of the Zn are stored in floodplain deposits. Most of the metal mass in channel deposits is stored near the mines, with 72% of the Pb and 78% of the Zn occurring in the 25 km of channel proximal to the mine source. Although environmental assessments of streams contaminated by mines often focus on evaluating metal concentrations in the geochemically active fine sediment fractions, about 60% of the Pb stored in channels is associated with coarse dolomite tailings fragments deposited in channels within 25 km of the mines. The magnitude and basinwide distribution of Pb and Zn storage in legacy floodplain sediments ensures that remobilization by bank erosion will be a continuing problem for water quality far into the future
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