565 research outputs found

    An oral delivery system for controlling white spot syndrome virus infection in shrimp using transgenic microalgae

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    White spot disease (WSD) is a longstanding and serious viral disease of various shrimp species that has caused high mortality rates for many decades. Currently, there is no practical method to control this disease. Therefore, we have explored the development of a novel vaccine-based method to control this disease using transgenic algae. During infection by white spot syndrome virus (WSSV), the interaction between viral envelope proteins and cell surface protein receptors on target cells is the key step of viral entry and replication. Hence, transgenic lines of the green microalga Chlamydomonas reinhardtii harbouring a WSSV VP28 viral envelope protein were created as an oral delivery system for vaccinating shrimp. Two separate transplastomic lines containing wild-type and codon optimized gene sequences for VP28 were evaluated for recombinant protein levels. Only the codon optimized line gave rise to detectable VP28 in western blot analysis, which demonstrated that optimization for chloroplast codon bias improved the efficiency of expression and that the gene design produced a favourable RNA secondary structure with suitable free energy for translation. In addition, bile salt and acid tolerance tests demonstrated that this transgenic Chlamydomonas can tolerate mildly acidic (pH 5.0) conditions and 0.30% bile salts. These features indicated that algal cells are suitable for delivering viral antigens through a shrimp's digestive system. In WSSV infection experiments, the highest survival rate (87%) was recorded in shrimps fed with the codon optimized VP28 line mixed into their feed, indicating that this line could be employed in the control of WSSV spread in shrimp populations. This algal strategy offers a new, efficient, fast and less labour-intensive method for the control of other diseases in aquatic animals through oral delivery

    Mutagenicity of comfrey (Symphytum Officinale) in rat liver

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    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant

    Delusions in frontotemporal lobar degeneration

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    We assessed the significance and nature of delusions in frontotemporal lobar degeneration (FTLD), an important cause of young-onset dementia with prominent neuropsychiatric features that remain incompletely characterised. The case notes of all patients meeting diagnostic criteria for FTLD attending a tertiary level cognitive disorders clinic over a three year period were retrospectively reviewed and eight patients with a history of delusions were identified. All patients underwent detailed clinical and neuropsychological evaluation and brain MRI. The diagnosis was confirmed pathologically in two cases. The estimated prevalence of delusions was 14 %. Delusions were an early, prominent and persistent feature. They were phenomenologically diverse; however paranoid and somatic delusions were prominent. Behavioural variant FTLD was the most frequently associated clinical subtype and cerebral atrophy was bilateral or predominantly right-sided in most cases. We conclude that delusions may be a clinical issue in FTLD, and this should be explored further in future work

    Energetics and stability of nanostructured amorphous carbon

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    Monte Carlo simulations, supplemented by ab initio calculations, shed light into the energetics and thermodynamic stability of nanostructured amorphous carbon. The interaction of the embedded nanocrystals with the host amorphous matrix is shown to determine in a large degree the stability and the relative energy differences among carbon phases. Diamonds are stable structures in matrices with sp^3 fraction over 60%. Schwarzites are stable in low-coordinated networks. Other sp^2-bonded structures are metastable.Comment: 11 pages, 7 figure

    Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring

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    Over the last 2 decades, a large number of neurophysiological and neuroimaging studies of patients with schizophrenia have furnished in vivo evidence for dysconnectivity, ie, abnormal functional integration of brain processes. While the evidence for dysconnectivity in schizophrenia is strong, its etiology, pathophysiological mechanisms, and significance for clinical symptoms are unclear. First, dysconnectivity could result from aberrant wiring of connections during development, from aberrant synaptic plasticity, or from both. Second, it is not clear how schizophrenic symptoms can be understood mechanistically as a consequence of dysconnectivity. Third, if dysconnectivity is the primary pathophysiology, and not just an epiphenomenon, then it should provide a mechanistic explanation for known empirical facts about schizophrenia. This article addresses these 3 issues in the framework of the dysconnection hypothesis. This theory postulates that the core pathology in schizophrenia resides in aberrant N-methyl-D-aspartate receptor (NMDAR)–mediated synaptic plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters like dopamine, serotonin, or acetylcholine. We argue that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups. Finally, we test the explanatory power of our theory against a list of empirical facts about schizophrenia

    Cerebellar Globular Cells Receive Monoaminergic Excitation and Monosynaptic Inhibition from Purkinje Cells

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    Inhibitory interneurons in the cerebellar granular layer are more heterogeneous than traditionally depicted. In contrast to Golgi cells, which are ubiquitously distributed in the granular layer, small fusiform Lugaro cells and globular cells are located underneath the Purkinje cell layer and small in number. Globular cells have not been characterized physiologically. Here, using cerebellar slices obtained from a strain of gene-manipulated mice expressing GFP specifically in GABAergic neurons, we morphologically identified globular cells, and compared their synaptic activity and monoaminergic influence of their electrical activity with those of small Golgi cells and small fusiform Lugaro cells. Globular cells were characterized by prominent IPSCs together with monosynaptic inputs from the axon collaterals of Purkinje cells, whereas small Golgi cells or small fusiform Lugaro cells displayed fewer and smaller spontaneous IPSCs. Globular cells were silent at rest and fired spike discharges in response to application of either serotonin (5-HT) or noradrenaline. The two monoamines also facilitated small Golgi cell firing, but only 5-HT elicited firing in small fusiform Lugaro cells. Furthermore, globular cells likely received excitatory monosynaptic inputs through mossy fibers. Because globular cells project their axons long in the transversal direction, the neuronal circuit that includes interplay between Purkinje cells and globular cells could regulate Purkinje cell activity in different microzones under the influence of monoamines and mossy fiber inputs, suggesting that globular cells likely play a unique modulatory role in cerebellar motor control

    Regional distribution of white matter hyperintensities in vascular dementia, Alzheimer's disease and healthy aging

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    Background: White matter hyperintensities (WMH) on MRI scans indicate lesions of the subcortical fiber system. The regional distribution of WMH may be related to their pathophysiology and clinical effect in vascular dementia (VaD), Alzheimer's disease (AD) and healthy aging. Methods: Regional WMH volumes were measured in MRI scans of 20 VaD patients, 25 AD patients and 22 healthy elderly subjects using FLAIR sequences and surface reconstructions from a three-dimensional MRI sequence. Results: The intraclass correlation coefficient for interrater reliability of WMH volume measurements ranged between 0.99 in the frontal and 0.72 in the occipital lobe. For each cerebral lobe, the WMH index, i.e. WMH volume divided by lobar volume, was highest in VaD and lowest in healthy controls. Within each group, the WMH index was higher in frontal and parietal lobes than in occipital and temporal lobes. Total WMH index and WMH indices in the frontal lobe correlated significantly with the MMSE score in VaD. Category fluency correlated with the frontal lobe WMH index in AD, while drawing performance correlated with parietal and temporal lobe WMH indices in VaD. Conclusions: A similar regional distribution of WMH between the three groups suggests a common (vascular) pathogenic factor leading to WMH in patients and controls. Our findings underscore the potential of regional WMH volumetry to determine correlations between subcortical pathology and cognitive impairment. Copyright (C) 2004 S. Karger AG, Basel
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