(G2019S) mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Twelve-to sixteen-month-old (G2019S) LRRK2 transgenic mice prepared by us displayed progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurons and parkinsonism phenotypes of motor dysfunction. LRRK2 is a member of mixed lineage kinase subfamily of mitogen-activated protein kinase kinase kinases (MAPKKKs). We hypothesized that (G2019S) mutation augmented LRRK2 kinase activity, leading to overphosphorylation of downstream MAPK kinase (MKK) and resulting in activation of neuronal death signal pathway. Consistent with our hypothesis, (G2019S) LRRK2 expressed in HEK 293 cells exhibited an augmented kinase activity of phosphorylating MAPK kinase 4 (MKK4) at Ser 257 , and protein expression of active phospho-MKK4 Ser257 was upregulated in the SN of (G2019S) LRRK2 transgenic mice. Protein level of active phospho-JNK Thr183/Tyr185 and phospho-c-Jun Ser63 , downstream targets of phospho-MKK4 Ser257 , was increased in the SN of (G2019S) LRRK2 mice. Upregulated mRNA expression of pro-apoptotic Bim and FasL, target genes of phospho-c-Jun Ser63 , and formation of active caspase-9, caspase-8 and caspase-3 were also observed in the SN of (G2019S) LRRK2 transgenic mice. Our results suggest that mutant (G2019S) LRRK2 activates MKK4-JNK-c-Jun pathway in the SN and causes the resulting degeneration of SNpc dopaminergic neurons in PD transgenic mice.

Dietary sodium and potassium intake can influence blood pressure. The effects of salt substitution on patients with hypertension and normotensive family member controls, however, have not been evaluated in a rural Chinese population. The objective of this study, accordingly, was to assess the long-term effects of salt substitution on blood pressure. We conducted a double-blind, randomized controlled trial among 200 families in rural China to establish the 2-year effects of a reduced-sodium, high-potassium salt substitute (65% sodium chloride, 25% potassium chloride, 10% magnesium sulfate) compared with normal salt (100% sodium chloride) on blood pressure. Of the 462 individuals in the trial, 372 completed the study (81%). For normotensive subjects, the mean overall difference in systolic and diastolic blood pressure between the two groups at the 24-month follow-up was 2 mm Hg (95% confidence interval (CI) 0-4 mm Hg, P<0.05) and 2 mm Hg (95% CI 1-3 mm Hg, P<0.05), respectively. For subjects with hypertension, the mean overall decrease in systolic blood pressure showed a 4-mm Hg (95% CI 2-6 mm Hg, P<0.05) decrease between the two groups. Diastolic blood pressure was not affected by salt use in the hypertensive group. Salt substitution lowers systolic blood pressure in hypertensive patients and lowers both systolic and diastolic blood pressure in normotensive controls. Salt substitution, therefore, may be an effective adjuvant therapy for hypertensive patients and the potential efficacy in preventing hypertension in normotensive individuals.

Our study suggested a distance of 1.5 mm to prevent implant damage to the underlying inferior alveolar nerve when biomechanical loading was taken into consideration.

We report on the InAs quantum dots (QDs) laser in the 1.55μm wavelength region grown by gas source molecular-beam epitaxy. The active region of the laser structure consists of fivefold-stacked InAs QD layers embedded in the InGaAsP layer. Ridge waveguide lasers were processed and continuous-wave mode operation was achieved between 20 and 70°C, with characteristic temperature of 69K. High internal quantum efficiency (56%) and low infinite length threshold current density (128A∕cm2 per QD layer) was obtained for the as-cleaved devices at room temperature. The lasing wavelength range between 1.556 and 1.605μm can be covered by varying the laser cavity length.