Early exposure to paraquat sensitizes dopaminergic neurons to subsequent silencing of PINK1 gene expression in mice

Environmental exposure, genetic modification, and aging are considered risky for Parkinson's disease (PD). How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. Paraquat is an herbicide commonly used for weed and grass control. Exposure to paraquat is associated with the increased incidence of PD. In contrast to familial PD, most sporadic PD cases do not have genetic mutation, but may suffer from partial dysfunction of neuron-protective genes as aging. Using conditional transgenic RNAi, we showed that temporal silencing of PINK1 expression in adult mice increased striatal dopamine, the phenotype that could not be induced by constitutive gene silencing. Moreover, early exposure to paraquat sensitized dopaminergic neurons to subsequent silencing of PINK1 gene expression, leading to a significant loss of dopaminergic neurons. Our findings suggest a novel pathogenesis of PD: exposure to environmental toxicants early in the life reduces the threshold of developing PD and partial dysfunction of neuron-protective genes later in the life initiates a process of progressive neurodegeneration to cross the reduced threshold of disease onset.     

Distributed sensor activation algorithm for target tracking with binary sensor networks

Target tracking with wireless sensor networks (WSNs) has been a hot research topic recently. Many works have been done to improve the algorithms for localization and prediction of a moving target with smart sensors. However, the results are frequently difficult to implement because of hardware limitations. In this paper, we propose a practical distributed sensor activation algorithm (DSA²) that enables reliable tracking with the simplest binary-detection sensors. In this algorithm, all sensors in the field are activated with a probability to detect targets or sleep to save energy, the schedule of which depends on their neighbor sensors’ behaviors. Extensive simulations are also shown to demonstrate the effectiveness of the proposed algorithm. Great improvement in terms of energy-quality tradeoff and excellent robustness of the algorithm are also emphasized in the simulations.     

Identification and validation of mouse sperm proteins correlated with epididymal maturation

Sperm need to mature in the epididymis to become capable of fertilization. To understand the molecular mechanisms of mouse sperm maturation, we conducted a proteomic analysis using saturation dye labeling to identify proteins of caput and cauda epididymal sperm that exhibited differences in amounts or positions on two-dimensional gels. Of eight caput epididymal sperm-differential proteins, three were molecular chaperones and three were structural proteins. Of nine cauda epididymal sperm-differential proteins, six were enzymes of energy metabolism. To validate these proteins as markers of epididymal maturation, immunoblotting and immunofluorescence analyses were performed. During epididymal transit, heat shock protein 2 was eliminated with the cytoplasmic droplet and smooth muscle γ-actin exhibited reduced fluorescence from the anterior acrosome while the signal intensity of aldolase A increased, especially in the principal piece. Besides these changes, we observed protein spots, such as glutathione S-transferase mu 5 and the E2 component of pyruvate dehydrogenase complex, shifting to more basic isoelectric points, suggesting post-translational changes such dephosphorylation occur during epididymal maturation. We conclude that most caput epididymal sperm-differential proteins contribute to the functional modification of sperm structures and that many cauda epididymal sperm-differential proteins are involved in ATP production that promotes sperm functions such as motility.     

Antioxidant properties of the mung bean flavonoids on alleviating heat stress

Background

It is a widespread belief in Asian countries that mung bean soup (MBS) may afford a protective effect against heat stress. Lack of evidence supports MBS conferring a benefit in addition to water.

Results

Here we show that vitexin and isovitexin are the major antioxidant components in mungbean (more than 96% of them existing in the bean seed coat), and both of them could be absorbed via gavage into rat plasma. In the plasma of rats fed with mungbean coat extract before or after exposure to heat stress, the levels of malonaldehyde and activities of lactate dehydrogenase and nitric oxide synthase were remarkably reduced; the levels of total antioxidant capacity and glutathione (a quantitative assessment of oxidative stress) were significantly enhanced.

Conclusions

Our results demonstrate that MBS can play additional roles to prevent heat stress injury. Characterization of the mechanisms underlying mungbean beneficial effects should help in the design of diet therapy strategies to alleviate heat stress, as well as provide reference for searching natural medicines against oxidative stress induced diseases.     

A Chinese Creutzfeldt-Jakob disease patient with E196K mutation in PRNP

Genetic Creutzfeldt-Jakob disease (gCJD) is caused by a range of mutations in the prion protein gene (PRNP) and account for approximately 10–15% of overall human prion diseases worldwide. They are different with disease onset, disease duration, clinical signs and diagnostic findings. Here we reported a 71 year-old female with an E196K mutation in one PRNP allele, while the codon 129 was a methionine homozygous genotype. The patient started with non-specific symptoms, but displayed rapidly progressive disturbances of speech, memory, cognitive and physical movement. No periodic activity was recorded at electroencephalography (EEG) during the entire disease course. Retrospective investigation of her family members did not reveal similar neurological disorders. Total clinical course was about seven months.Key words: Creutzfeldt-Jakob disease, PRNP, E196K     

The epidemiological, clinical, and laboratory features of sporadic Creutzfeldt-Jakob disease patients in China: surveillance data from 2006 to 2010

Background

Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive fatal central nervous system disorder, which consists of three main catalogues: sporadic, familial, and iatrogenic CJD.

Methodology/Principal Findings

In China, the surveillance for CJD started in 2006, covering 12 provincial Centers for Disease Control and Prevention (CDCs) and 15 hospitals. From 2006 to 2010, 624 suspected patients were referred to China CJD surveillance. The epidemiological, clinical and laboratory features of sporadic CJD (sCJD) were analysed. Both groups of probable and possible sCJD showed highest incidences in the population of 60 to 69 year-olds. The most common presenting symptoms were progressive dementia and mental-related symptoms (neurological symptoms including sleeping turbulence, depression, anxiety and stress). Among the four main clinical manifestations, myoclonus was more frequently observed in the probable sCJD patients. About 2/3 of probable sCJD cases showed positive 14-3-3 in CSF and/or periodic sharp wave complexes (PSWC) in electroencephalography (EEG). The presence of myoclonus was significantly closely related with the appearance of PSWC in EEG. Polymorphisms of codon 129 in PRNP of the notified cases revealed a highly predominant M129M genotype in Han Chinese. Among 23 genetic human prion diseases, ten were D178N/M129M Fatal familial insomnia (FFI) and five were T188K genetic CJD (gCJD), possibly indicating a special distribution of gCJD-related mutations in Han Chinese.

Conclusion

From the period of 2006 to 2010, 261 patients were diagnosed as sCJD and 23 patients were diagnosed as genetic human prion diseases in China. The epidemiological, clinical and laboratory analysis data were consistent with the characteristics of sporadic CJD, which provide insight into the features of CJD in China.     

The first Chinese case of Creutzfeldt-Jakob disease patient with R208H mutation in PRNP

A case of Creutzfeldt-Jakob disease (CJD) with a rare mutation of the prion protein (PrP) gene (PRNP) at codon 208 (R208H), while the codon 129 was a methionine homozygous genotype is reported. The patient initial displayed hand tremor, dizziness and progressive cognitive dysfunction. Subsequently, other symptoms gradually appeared, including cerebellar ataxia and mental disorder. No periodic activity was recorded at electroencephalography (EEG) and 14-3-3 protein in cerebrospinal fluid was negative. Total clinical course was about four months. Retrospective investigation of this family across seven generations did not figure out clear family history. However, genetic analyses revealed six first-degree family members with the R208H allele.Key words: creutzfeldt-Jakob disease, PRNP, R208H     

Leptospira interrogans encodes an ROK family glucokinase involved in a cryptic glucose utilization pathway

Although Leptospira interrogans is unable to utilize glucose as its carbon/energy source, the LA_1437 gene of L. interrogans serovar Lai potentially encodes a group III glucokinase (GLK). The L. interrogans GLK (LiGLK) heterogeneously expressed in Escherichia coli was purified and proved to be a homodimeric enzyme with its specific activity of 12.3 ± 0.6 U/mg x protein determined under an improved assay condition (pH 9.0, 50 ° C), 7.5-fold higher than that assayed under the previously used condition (pH 7.3, 25 ° C). The improved sensitivity allowed us to detect this enzymatic activity of (5.0 ± 0.6) × 10(-3) U/mg x protein in the crude extract of L. interrogans serovar Lai cultured in standard Ellinghausen-McCullough-Johnson-Harris medium. The k(cat) and K(m) values for d-glucose and ATP were similar to those of other group III GLKs, although the K(m) value for ATP was slightly higher. Site-directed mutagenesis analysis targeting the conserved amino acid residues in the potential ATP-binding motif hinted that a proper array of Gly residues in the motif might be important for maintaining the conformation that was essential for its function. Gene expression profiling and quantitative proteomic data mining provided preliminary evidence for the absence of efficient systems involved in glucose transport and glycolysis that might account for the failure of glucose utilization in L. interrogans.