Editorial

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Regulation of LRRK2 Stability by the E3 Ubiquitin Ligase CHIP

Dominantly inherited mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common cause of familial Parkinson's disease (PD) and have also been identified in individuals with sporadic PD. Although the exact cellular function of LRRK2 remains unknown, most PD-linked mutations appear to be toxic to cells in culture via mechanisms that depend on the kinase activity of LRRK2 or on the formation of cytoplasmic inclusions. Here we show that the E3 ubiquitin ligase CHIP physically associates with LRRK2 and regulates the cellular abundance of LRRK2. We further show that LRRK2 forms a complex with overexpressed and endogenous CHIP and Hsp90. Our data indicates that the destabilization of LRRK2 by CHIP is due to ubiquitination and proteasome-dependent degradation. Hsp90 can attenuate CHIP-mediated degradation and this can be blocked by the Hsp90 inhibitor geldanamycin. These findings provide important insight into the cellular regulation of LRRK2 stability and may lead to the development of therapeutics to treat PD based on controlling LRRK2 stability

Correct order on some certain weighted representation functions

Let $\mathbb{N}$ be the set of all nonnegative integers. For any positive integer $k$ and any subset $A$ of nonnegative integers, let $r_{1,k}(A,n)$ be the number of solutions $(a_1,a_2)$ to the equation $n=a_1+ka_2$. In 2016, Qu proved that $$\liminf_{n\rightarrow\infty}r_{1,k}(A,n)=\infty$$ providing that $r_{1,k}(A,n)=r_{1,k}(\mathbb{N}\setminus A,n)$ for all sufficiently large integers, which answered affirmatively a 2012 problem of Yang and Chen. In a very recent article, another Chen (the first named author) slightly improved Qu's result and obtained that $$\liminf_{n\rightarrow\infty}\frac{r_{1,k}(A,n)}{\log n}>0.$$ In this note, we further improve the lower bound on $r_{1,k}(A,n)$ by showing that $$\liminf_{n\rightarrow\infty}\frac{r_{1,k}(A,n)}{n}>0.$$ Our bound reflects the correct order of magnitude of the representation function $r_{1,k}(A,n)$ under the above restrictions due to the trivial fact that $r_{1,k}(A,n)\le n/k.

The effects of dog management on Echinococcus spp. prevalence in villages on the eastern Tibetan Plateau, China

Background The pastoral area of the eastern Tibetan plateau is a very important human echinococcosis endemic region. Domestic dogs are the main definitive host for the transmission of Echinococcus granulosus sensu lato (s.1.) and E. multilocularis to humans. To control the infection risks, a national-level canine echinococcosis prevention and control program has been implemented since 2015 in Shiqu County, Sichuan, China, The objective of this investigation was to evaluate its effect on Echinococcus spp. prevalence in dogs. Methods We surveyed 69 households with 84 owned dogs, for dog keeping information in the villages of Rizha and Eduoma. A total of 105 dog fecal samples, consisting of 75 from owned dogs and 30 unknown dog fecal samples were collected between 2015 and 2017 to determine Echinococcus spp. prevalence using copro-PCR. Eight variables based on household surveys were included into a logistic regression model for significantly relevant factors to canine echinococcosis prevalence in dogs. Results The overall Echinococcus spp. copro-DNA prevalence decreased significantly in dogs from 51.2% (2015) to 20.0% (2017) in Rizha, and insignificantly from 11.5% (2016) to 4.3% (2017) in Eduoma. Echinococcus multilocularis was the most prevalent species continually detected during the entire research period, while E. granulosus was rare and not detected in 2017. Echinococcus shiquicus prevalence was as high as E. multilocularis , although only detected in 2015 in Rizha. Unleashed dog feces were mainly collected in Rizha Village in 2015. Although 93.2% of owned dogs were leashed, and the monthly praziquantel dosing rate reached 97%, E. multilocularis infection could still be detected in 11.1% of owned dogs in 2017. Monthly deworming, leashing dogs 24h per day, and the avoidance of dogs feeding on livestock viscera are significant measures to prevent canine echinococcosis infection in owned dogs. Conclusion Carrying out a canine echinococcosis prevention and control program can significantly decrease the Echinococcus prevalence. The potential contact between leashed dogs and wild small mammals is still a risk to re-infect owned dogs. This study shows that the long term application of regular dog dosing in the vast remote echinococcosis endemic areas of west China is still challenging