MALT1 is a potential therapeutic target in glioblastoma and plays a crucial role in EGFR‐induced NF‐κB activation

Glioblastoma multiforme (GBM) is the most common malignant tumour in the adult brain and hard to treat. Nuclear factor κB (NF‐κB) signalling has a crucial role in the tumorigenesis of GBM. EGFR signalling is an important driver of NF‐κB activation in GBM; however, the correlation between EGFR and the NF‐κB pathway remains unclear. In this study, we investigated the role of mucosa‐associated lymphoma antigen 1 (MALT1) in glioma progression and evaluated the anti‐tumour activity and effectiveness of MI‐2, a MALT1 inhibitor in a pre‐clinical GBM model. We identified a paracaspase MALT1 that is involved in EGFR‐induced NF‐kB activation in GBM. MALT1 deficiency or inhibition significantly affected the proliferation, survival, migration and invasion of GBM cells both in vitro and in vivo. Moreover, MALT1 inhibition caused G1 cell cycle arrest by regulating multiple cell cycle–associated proteins. Mechanistically, MALTI inhibition blocks the degradation of IκBα and prevents the nuclear accumulation of the NF‐κB p65 subunit in GBM cells. This study found that MALT1, a key signal transduction cascade, can mediate EGFR‐induced NF‐kB activation in GBM and may be potentially used as a novel therapeutic target for GBM.     

罗霄山脉翼手目物种多样性及适生区预测

罗霄山脉位于中国大陆东南部, 是一条南北走向的大型山脉, 面积约6.76万km²。该山脉位于欧亚大陆东部季风区, 生物多样性丰富, 是亚洲东部第三纪冰期动物重要的避难所。为了解罗霄山脉翼手目物种多样性状况, 本研究组于2013-2018年, 使用雾网、手网和竖琴网等工具开展了针对性调查与标本采集, 同时运用形态分类学和分子系统发生学方法鉴定物种。根据调查结果并结合文献记载: 罗霄山脉地区现有翼手目物种4科14属40种, 其中罗霄山脉翼手目新记录种25种, 省级翼手目分布新记录种9种。同时, 本研究基于5年的调查采集位点, 使用生物多样 性与气候变化虚拟实验室(the Biodiversity & Climate Change Virtual Laboratory)在线生境预测平台, 对罗霄山脉翼手目物种当前的适生区, 以及3种不同量温室气体排放情景下(representative concentration pathway, RCP 2.6 / 6.0 / 8.5) 2050年的适生区进行预测, 其中随机森林算法(random forest)的模型解释力较优, 其预测结果显示: 影响该区域翼手目分布的主要环境因子为降水季节性和年平均温度; 山脉中部及南部为翼手目的高适生区, 面积约为罗霄山脉的30%; 与当前适生区相比, RCP 2.6情景下2050年该类群适生区有所扩增, RCP 6.0和RCP 8.5情景下均会导致翼手目适生区急剧缩减, 且分布区将迁移至高海拔区域以响应气候变化。而本项目的开展不仅初步掌握了罗霄山脉翼手目物种多样性本底状况, 也为开展后续的翼手目研究和保护管理提供了参考。     

Influences of low-head dams on the fish assemblages in the headwater streams of the Qingyi watershed, China

The influences of low-head dams on the fish assemblages were examined in this study, using fish data collected in six treatment and five reference sites at three low-head dams in the headwater streams of the Qingyi watershed, China. Comparing with those in the reference sites, local habitat variables were significantly altered by low-head dams in the treatment sites, involving wider channel (only in the impoundment area), deeper water and slower flow. Fish species richness varied significantly across seasons, not across site categories, suggesting that these low-head dams did not alter species richness. However, significant decreases in fish abundance and density were observed in the impoundment areas immediately upstream of dams, but not in the plunge areas downstream. Fish assemblage structures kept relative stability across seasons, and their significant difference between-site was only observed between the impoundment areas and the sites far from dams upstream. This variation in assemblage structures was due to the differing relative abundance of some co-occurring species; more lentic but less lotic fish was observed in the impoundment areas. The spatial and temporal patterns of fish assemblages were correlated with local habitat in this study area. Wetted width had negative correlation with fish species richness, abundance and density, respectively. Water temperature also positively affected species richness. In addition, wetted width, water depth, current velocity and substrate were the important habitat variables influencing assemblage structures. Our results suggested that, by modifying local habitat characteristics, low-head dams altered fish abundance and density in the impoundment areas immediately upstream of dam, not in the plunge areas immediately downstream, and thereby influenced fish assemblage structures in these stream segments.     

A single amino acid determines the catalytic efficiency of two alkenal double bond reductases produced by the liverwort Plagiochasma appendiculatum

Alkenal double bond reductases (DBRs) catalyze the NADPH-dependent reduction of the α,β-unsaturated double bond of many secondary metabolites. Two alkenal double bond reductase genes PaDBR1 and PaDBR2 were isolated from the liverwort species Plagiochasma appendiculatum. Recombinant PaDBR2 protein had a higher catalytic activity than PaDBR1 with respect to the reduction of the double bond present in hydroxycinnamyl aldehydes. The residue at position 56 appeared to be responsible for this difference in enzyme activity. The functionality of a C56 to Y56 mutation in PaDBR1 was similar to that of PaDBR2. Further site-directed mutagenesis and structural modeling suggested that the phenol ring stacking between this residue and the substrate was an important determinant of catalytic efficiency.     

The non-negative matrix factorization toolbox for biological data mining

Background

Non-negative matrix factorization (NMF) has been introduced as an important method for mining biological data. Though there currently exists packages implemented in R and other programming languages, they either provide only a few optimization algorithms or focus on a specific application field. There does not exist a complete NMF package for the bioinformatics community, and in order to perform various data mining tasks on biological data.

Results

We provide a convenient MATLAB toolbox containing both the implementations of various NMF techniques and a variety of NMF-based data mining approaches for analyzing biological data. Data mining approaches implemented within the toolbox include data clustering and bi-clustering, feature extraction and selection, sample classification, missing values imputation, data visualization, and statistical comparison.

Conclusions

A series of analysis such as molecular pattern discovery, biological process identification, dimension reduction, disease prediction, visualization, and statistical comparison can be performed using this toolbox.

     

Expression and signal regulation of the alternative oxidase genes under abiotic stresses

Plants in their natural environment frequently face various abiotic stresses, such as drought, high salinity, and chilling. Plant mitochondria contain an alternative oxidase （AOX）, which is encoded by a small family of nuclear genes. AOX genes have been shown to be highly responsive to abiotic stresses. Using transgenic plants with varying levels of AOX expression, it has been confirmed that AOX genes are im- portant for abiotic stress tolerance. Although the roles of AOX under abiotic stresses have been extensively studied and there are several excellent reviews on this topic, the differential expression patterns of the AOX gene family members and the signal regulation of AOX gene（s） under abiotic stresses have not been extensively summarized. Here, we review and discuss the current progress of these two important issues.