The C9orf72-SMCR8-WDR41 complex is a GAP for small GTPases

ABSTRACT

Massive expansions of the hexanucleotide in C9orf72 are the primary genetic origins of familial amyotrophic lateral sclerosis (ALS) and frontal temporal dementia (FTD). Current studies have found that this repeat sequence participates in the disease process by producing neurotoxic substances and reducing the level of C9orf72 protein; however, the progress in the functional study of C9orf72 is slow. Recently, a stable complex, consisting of C9orf72, SMCR8, and WDR41, has been implicated in regulating membrane trafficking and macroautophagy. We reported the cryo-electron microscopy (cryo-EM) structure of the C9orf72-SMCR8-WDR41 complex (CSW complex), unveiling that the CSW complex is a dimer of heterotrimers. Intriguingly, in the heterotrimer of the C9orf72-SMCR8-WDR41, C9orf72 interacts with SMCR8 in a manner similar to the FLCN-FNIP2 complex. Nevertheless, WDR41 is connected to the DENN domain of SMCR8 through its N-terminal β-strand and C-terminal helix but does not directly interact with C9orf72. Notably, the C9orf72-SMCR8 complex was demonstrated to act as a GAP for RAB8A and RAB11A in vitro.     

Reviving exhausted T lymphocytes during chronic virus infection by B7-H1 blockade

Cytotoxic T lymphocytes (CTLs) are killer cells that are crucial in the control of viral pathogens and cancers. They can become exhausted during chronic viral infection, a phenomenon that consists of a reduction in both number and functionality of CTLs. Recently, Barber and colleagues demonstrated that B7-H1 (also called PD-L1), a cell-surface molecule that is widely distributed in tissues, was necessary for the maintenance of T-cell exhaustion in a chronic-infection mouse model of lymphocytic choriomeningitis virus (LCMV). PD-1, the receptor of B7-H1, was greatly upregulated on CTLs in response to LCMV, and its expression was maintained during chronic infection. Blockade of the B7-H1-PD-1 pathway by a monoclonal antibody restored CTL function and reduced viral burden. These results suggest a new strategy for the treatment of chronic viral infection.     

A tale of two cyclists: a cross-cultural comparison between Taiwanese and Filipino perceptions on cycling infrastructure landscapes

How is cycling culture defined? Because the word “culture” brings with it deep complexities, there is a need to understand varying contexts in looking for suitable strategies toward the advancement of cycling culture. The stage for cycling culture is the landscape where cycling infrastructure can be properly provided. With development, an influential element would be economic capacity. The paper explores the influence of the economic development divide by comparing cyclist perception between developed and developing countries, namely Taiwan and the Philippines. An online survey between 122 Taiwanese and 111 Filipino cyclists was conducted to find out the landscape needs of people to consider cycling transport based on affordances in the landscape. The variables selected were based on landscape elements for cycling as a commuting activity. The data were processed through factor analysis to reveal latent landscape needs to profile cycling needs. Two factors were identified as ‘environmental’ and ‘civil facilities.’ The factor loadings were then compared based on the nationalities which revealed that the bike riding motivation were different with relating to the context of their respective environment and similar with the basic infrastructural demands.

     

Indoor Thin‐Film Photovoltaics: Progress and Challenges

Energy generation and consumption have always been an important component of social development. Interests in this field are beginning to shift to indoor photovoltaics (IPV) which can serve as power sources under low light conditions to meet the energy needs of rapidly growing fields, such as intelligence gathering and information processing which usually operate via the Internet‐of‐things (IoT). Since the power requirements for this purpose continue to decrease, IPV systems under low light may facilitate the realization of self‐powered high‐tech electronic devices connected through the IoT. This review discusses and compares the characteristics of different types of IPV devices such as those based on silicon, dye, III‐V semiconductors, organic compounds, and halide perovskites. Among them, specific attention is paid to perovskite photovoltaics which may potentially become a high performing IPV system due to the fascinating photophysics of the halide perovskite active layer. The limitations of such indoor application as they relate to the toxicity, stability, and electronic structure of halide perovskites are also discussed. Finally, strategies which could produce highly functional, nontoxic, and stable perovskite photovoltaics devices for indoor applications are proposed.     

The Physiological Effects of Ethrel on Seedlings of Second Season Rice

Spray of ethrel (1000 ppm)to seedlings of double-cropping second season rice at 5-leaf stage can control plant height and root length, and consequently makes seedlings strong and tough. The ABA content and ethylene released by young seedling were significantly higher than the control. However, there were some changes: cell elongation inhibited, leaf area decreased, and leaf color became dark green, photosynthetic rate increased, translocation of photosynthetate in leaf sheath enhanced, leaf emergence was rapid. The growth of root system and root vigor were though temporarily inhibited, but slightly increased after transplantation. All these are beneficial to seedling quality, the plant growth and development after transplantation, which subsequently bring about positive effects on stimulating early heading and on increasing rice yield.     

Topoisomerase I‐Mediated Antiproliferative Activity of 10‐Substituted and 12‐Substituted Homocamptothecins

Homocamptothecin (hCPT) is an E‐ring modified camptothecin (CPT) analogue, which showed pronounced inhibitory activity of topoisomerase I. In search of novel hCPT‐type anticancer agents, two series of hCPT derivatives were synthesized and evaluated in vitro against three human tumor cell lines. The results indicated that the 10‐substituted hCPT derivatives had a considerably higher cytotoxic activity than the 12‐substituted ones. Among the 10‐substituted compounds, 8a, 8b, 9b , and 9i showed an equivalent or even more potent activity than the positive control drug topotecan against the lung cancer cell line A‐549. Moreover, the hCPT analogues 8a and 8b exhibited a higher topoisomerase I inhibitory activity than CPT at a concentration of 100 μM .