BackgroundLeucine-rich repeat kinase 2 (LRRK2) is the gene responsible for autosomal-dominant Parkinson’s disease (PD), PARK8, but the mechanism by which LRRK2 mutations cause neuronal dysfunction remains unknown. In the present study, we investigated for the first time a transgenic (TG) mouse strain expressing human LRRK2 with an I2020T mutation in the kinase domain, which had been detected in the patients of the original PARK8 family.ResultsThe TG mouse expressed I2020T LRRK2 in dopaminergic (DA) neurons of the substantia nigra, ventral tegmental area, and olfactory bulb. In both the beam test and rotarod test, the TG mice exhibited impaired locomotive ability in comparison with their non-transgenic (NTG) littermates. Although there was no obvious loss of DA neurons in either the substantia nigra or striatum, the TG brain showed several neurological abnormalities such as a reduced striatal dopamine content, fragmentation of the Golgi apparatus in DA neurons, and an increased degree of microtubule polymerization. Furthermore, the tyrosine hydroxylase-positive primary neurons derived from the TG mouse showed an increased frequency of apoptosis and had neurites with fewer branches and decreased outgrowth in comparison with those derived from the NTG controls.ConclusionsThe I2020T LRRK2 TG mouse exhibited impaired locomotive ability accompanied by several dopaminergic neuron abnormalities. The TG mouse should provide valuable clues to the etiology of PD caused by the LRRK2 mutation.
Objective. The aim of this systematic review is to evaluate the efficacy and safety of herbal medicines in the management of metabolic syndrome. Materials and Methods. On December 9, 2015, we searched PubMed, EMBASE, Cochrane Library, SCOPUS, AMED, CNKI, KoreaMed, KMBASE, OASIS, and J-STAGE with no restriction on language or published year. We selected randomized controlled trials that involved patients with metabolic syndrome being treated with herbal medicines as intervention. The main keywords were “Chinese herbal medicines”, “metabolic syndrome”, and “randomized controlled trials”. Herbal substances which were not based on East Asian medical theory, combination therapy with western medicines, and concurrent diseases other than metabolic syndrome were excluded. The risk of bias was assessed by Cochrane's “Risk of Bias” tool. The protocol or review was registered in PROSPERO (an international prospective register of systematic reviews) (CRD42014006842). Results. From 1,098 articles, 12 RCTs were included in this review: five trials studied herbal medicines versus a placebo or no treatment, and seven trials studied herbal medicines versus western medicines. Herbal medicines were effective on decreasing waist circumference, blood glucose, blood lipids, and blood pressure. Conclusion. This study suggests the possibility that herbal medicines can be complementary and alternative medicines for metabolic syndrome.
In recent high-density and low-power VLSIs, soft errors occurring on not only memory systems and the latches of logic circuits but also the combinational parts of logic circuits seriously affect the operation of systems. The conventional soft error tolerant methods for soft errors on the combinational parts do not provide enough high soft error tolerant capability with small performance penalty. This paper proposes a class of soft error masking circuits by using a Schmitt trigger circuit and pass transistors. The paper also presents construction of soft error masking latches (SEM-Latches) capable of masking transient pulses occurring on combinational circuits. Moreover, experimental results show that the proposed method has higher soft error tolerant capability than the existing methods. For driving voltage VDD=3.3V, the proposed method is capable of masking transient pulses of magnitude 4.0V or less.
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