1,568 research outputs found

    Detrital zircon geochronology and evolution of the Nacimiento block late Mesozoic forearc basin, central California coast

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    Forearc basins are first-order products of convergent-margin tectonics, and their sedimentary deposits offer unique perspectives on coeval evolution of adjacent arcs and subduction complexes. New detrital zircon U-Pb geochronologic data from 23 sandstones and 11 individual conglomerate clasts sampled from forearc basin strata of the Nacimiento block, an enigmatic stretch of the Cordilleran forearc exposed along the central California coast, place constraints on models for forearc deformation during evolution of the archetypical Cordilleran Mesozoic margin. Deposition and provenance of the Nacimiento forearc developed in three stages: (1) Late Jurassic– Valanginian deposition of lower Nacimiento forearc strata with zircon derived from the Jurassic–Early Cretaceous arc mixed with zircon recycled from Neoproterozoic– Paleozoic and Mesozoic sedimentary sources typical of the continental interior; (2) erosion or depositional hiatus from ca. 135 to 110 Ma; and (3) Albian–Santonian deposition of upper Nacimiento forearc strata with zircon derived primarily from the Late Cretaceous arc, accompanied by Middle Jurassic zircon during the late Albian–Cenomanian. These data are most consistent with sedimentary source terranes and a paleogeographic origin for the Nacimiento block south of the southern San Joaquin Basin in southern California or northernmost Mexico. This interpreted paleogeographic and depositional history of the Nacimiento block has several implications for the tectonic evolution of the southern California Mesozoic margin. First, the Nacimiento forearc depositional history places new timing constraints on the Early Cretaceous unconformity found in forearc basin strata from the San Joaquin Valley to Baja California. This timing constraint suggests a model in which forearc basin accommodation space was controlled by accretionary growth of the adjacent subduction complex, and where tectonic events in the forearc and the arc were linked through sediment supply rather than through orogenic-scale wedge dynamics. Second, a paleogeographic origin for the Nacimiento forearc south of the southern San Joaquin Valley places new constraints on end-member models for the kinematic evolution of the Sur-Nacimiento fault. Although this new paleogeographic reconstruction cannot distinguish between sinistral strike-slip and thrust models, it requires revision of existing sinistral-slip models for the Sur-Nacimiento fault, and it highlights unresolved problems with the thrust model

    Postsynaptic Signals Mediating Induction of Long-Term Synaptic Depression in the Entorhinal Cortex

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    The entorhinal cortex receives a large projection from the piriform cortex, and synaptic plasticity in this pathway may affect olfactory processing. In vitro whole cell recordings have been used here to investigate postsynaptic signalling mechanisms that mediate the induction of long-term synaptic depression (LTD) in layer II entorhinal cortex cells. To induce LTD, pairs of pulses, using a 30-millisecond interval, were delivered at 1 Hz for 15 minutes. Induction of LTD was blocked by the NMDA receptor antagonist APV and by the calcium chelator BAPTA, consistent with a requirement for calcium influx via NMDA receptors. Induction of LTD was blocked when the FK506 was included in the intracellular solution to block the phosphatase calcineurin. Okadaic acid, which blocks activation of protein phosphatases 1 and 2a, also prevented LTD. Activation of protein phosphatases following calcium influx therefore contributes to induction of LTD in layer II of the entorhinal cortex

    Muscarinic Depolarization of Layer II Neurons of the Parasubiculum

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    The parasubiculum (PaS) is a component of the hippocampal formation that sends its major output to layer II of the entorhinal cortex. The PaS receives strong cholinergic innervation from the basal forebrain that is likely to modulate neuronal excitability and contribute to theta-frequency network activity. The present study used whole cell current- and voltage-clamp recordings to determine the effects of cholinergic receptor activation on layer II PaS neurons. Bath application of carbachol (CCh; 10–50 µM) resulted in a dose-dependent depolarization of morphologically-identified layer II stellate and pyramidal cells that was not prevented by blockade of excitatory and inhibitory synaptic inputs. Bath application of the M1 receptor antagonist pirenzepine (1 µM), but not the M2-preferring antagonist methoctramine (1 µM), blocked the depolarization, suggesting that it is dependent on M1 receptors. Voltage-clamp experiments using ramped voltage commands showed that CCh resulted in the gradual development of an inward current that was partially blocked by concurrent application of the selective Kv7.2/3 channel antagonist XE-991, which inhibits the muscarine-dependent K+ current IM. The remaining inward current also reversed near EK and was inhibited by the K+ channel blocker Ba2+, suggesting that M1 receptor activation attenuates both IM as well as an additional K+ current. The additional K+ current showed rectification at depolarized voltages, similar to K+ conductances mediated by Kir 2.3 channels. The cholinergic depolarization of layer II PaS neurons therefore appears to occur through M1-mediated effects on IM as well as an additional K+ conductance

    Does stakeholder involvement really benefit biodiversity conservation?

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    The establishment of protected areas, such as Natura 2000, is a common approach to curbing biodiversity loss. But many of these areas are owned or managed by private actors. Policies indicate that their involvement should be encouraged to ensure long term success. However, to date there have been no systematic evaluations of whether local actor involvement in the management of protected areas does in fact contribute to the conservation of biodiversity, which is the expressed policy goal. Research incorporating both qualitative and quantitative data was carried out in three case studies in Scotland where local actor input was required in the development and/or implementation of Natura 2000 management plans. No relationship was found between the characteristics of the process of stakeholder involvement and stakeholders’ perceptions of future biodiversity outcomes. Social outcomes of increased stakeholder involvement, such as increased trust, did however increase the perceived likelihood of positive future biodiversity outcomes. The findings indicate that efforts aimed at increasing stakeholder involvement in the management of protected areas need to consider making processes more independent, and acknowledge and address underlying biodiversity conflicts. The findings also emphasise the need to evaluate multi-level conservation efforts in terms of processes, social outcomes and biodiversity outcomes

    Identification of harmful cyanobacteria in the Sacramento-San Joaquin Delta and Clear Lake, California by DNA barcoding.

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    Accurate identification of cyanobacteria using traditional morphological taxonomy is challenging due to the magnitude of phenotypic plasticity among natural algal assemblages. In this study, molecular approach was utilized to facilitate the accurate identification of cyanobacteria in the Sacramento-San Joaquin Delta and in Clear Lake in Northern California where recurring blooms have been observed over the past decades. Algal samples were collected from both water bodies in 2011 and the samples containing diverse cyanobacteria as identified by morphological taxonomy were chosen for the molecular analysis. The 16S ribosomal RNA genes (16S rDNA) and the adjacent internal transcribed spacer (ITS) regions were amplified by PCR from the mixed algal samples using cyanobacteria generic primers. The obtained sequences were analyzed by similarity search (BLASTN) and phylogenetic analysis (16S rDNA) to differentiate species sharing significantly similar sequences. A total of 185 plasmid clones were obtained of which 77 were successfully identified to the species level: Aphanizomenon flos-aquae, Dolichospermum lemmermannii (taxonomic synonym: Anabaena lemmermannii), Limnoraphis robusta (taxonomic synonym: Lyngbya hieronymusii f. robusta) and Microcystis aeruginosa. To date, Dolichospermum and Limnoraphis found in Clear Lake have only been identified to the genus lavel by microscopy. During the course of this study, morphological identification and DNA barcoding confirmed A. flos-aquae as the predominant cyanobacterium in the Sacramento-San Joaquin Delta indicating a shift from M. aeruginosa that have dominated the blooms in the past decade. Lastly, the species-specific identification of Limnoraphis robusta in Clear Lake is another significant finding as this cyanobacterium has, thus far, only been reported in Lake Atitlan blooms in Guatemala

    The Human Gene Mutation Database (HGMD®): optimizing its use in a clinical diagnostic or research setting

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    The Human Gene Mutation Database (HGMD®) constitutes a comprehensive collection of published germline mutations in nuclear genes that are thought to underlie, or are closely associated with human inherited disease. At the time of writing (June 2020), the database contains in excess of 289,000 different gene lesions identified in over 11,100 genes manually curated from 72,987 articles published in over 3100 peer-reviewed journals. There are primarily two main groups of users who utilise HGMD on a regular basis; research scientists and clinical diagnosticians. This review aims to highlight how to make the most out of HGMD data in each setting

    Polyfluoroaromatic stavudine (d4T) ProTides exhibit enhanced anti-HIV activity

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    Human Immunodeficiency Virus (HIV) damages the immune system and leads to the life-threatening acquired immunodeficiency syndrome (AIDS). Despite the advances in the field of antiretroviral treatment, HIV remains a major public health challenge. Nucleosides represent a prominent chemotherapeutic class for treating viruses, however their cellular uptake, kinase-mediated activation and catabolism are limiting factors. Herein, we report the synthesis and in vitro evaluation of stavudine (d4T) ProTides containing polyfluorinated aryl groups against two strains; HIV-1 (IIIB) and HIV-2 (ROD). ProTide 5d containing a meta-substituted pentafluorosulfanyl (3-SF5) aryl group showed superior antiviral activity over the parent d4T and the nonfluorinated analogue 5a. ProTide 5d has low nanomolar antiviral activity; (IC50 = 30 nM, HIV-1) and (IC50 = 36 nM, HIV-2) which is over tenfold more potent than d4T. Interestingly, ProTide 5d showed a significantly high selectivity indices with SI = 1753 (HIV-1) and 1461 (HIV-2) which is more than twice that of the d4T. All ProTides were screened in wild type as well as thymidine kinase deficient (TK−) cells. Enzymatic activation of ProTide 5d using carboxypeptidase Y enzyme and monitored using both 31P and 19F NMR is presented
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