Atg21p is essential for macropexophagy and microautophagy in the yeast Hansenula polymorpha

ATG genes are required for autophagy-related processes that transport proteins/organelles destined for proteolytic degradation to the vacuole. Here, we describe the identification and characterisation of the Hansenula polymorpha ATG21 gene. Its gene product Hp-Atg21p, fused to eGFP, had a dual location in the cytosol and in peri-vacuolar dots. We demonstrate that Hp-Atg21p is essential for two separate modes of peroxisome degradation, namely glucose-induced macropexophagy and nitrogen limitation-induced microautophagy. In atg21 cells subjected to macropexophagy conditions, sequestration of peroxisomes tagged for degradation is initiated but fails to complete.     

青藏公路对高原鼠兔种内遗传分化的影响

研究采用7个微卫星标记分析在青海省西大滩区域,位于青藏公路两侧的4个高原鼠兔（Ochotona curzoniae）种群的遗传变异情况。分别采用软件TFPGA和GENE POP3．4计算各种群间的Nei’s标准遗传距离,基因分化系数（Fst）等参数,并对遗传距离进行UPGMA聚类分析。研究结果表明,公路同侧种群间平均遗传距离和基因分化系数分别为0．0808和0．0541;异侧种群间平均遗传距离和基因分化系数分别为0．1037和0．0705,公路东侧和西侧的两个种群分别聚为一类。青藏公路对分布于公路两侧的高原鼠兔种群间的基因交流产生了一定的阻隔效应,并导致种群间出现了一定程度的遗传分化。     

Plasma Membrane Tetraspanin CD81 Complexes with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and Low Density Lipoprotein Receptor (LDLR), and Its Levels Are Reduced by PCSK9

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important factor in plasma cholesterol regulation through modulation of low density lipoprotein receptor (LDLR) levels. Naturally occurring mutations can lead to hyper- or hypocholesterolemia in human. Recently, we reported that PCSK9 was also able to modulate CD81 in Huh7 cells. In the present study, several gain-of-function and loss-of-function mutants as well as engineered mutants of PCSK9 were compared for their ability to modulate the cell surface expression of LDLR and CD81. Although PCSK9 gain-of-function D374Y enhanced the degradation both receptors, D374H and D129N seemed to only reduce LDLR levels. In contrast, mutations in the C-terminal hinge-cysteine-histidine-rich domain segment primarily affected the PCSK9-induced CD81 degradation. Furthermore, when C-terminally fused to an ACE2 transmembrane anchor, the secretory N-terminal catalytic or hinge-cysteine-histidine-rich domain domains of PCSK9 were able to reduce CD81 and LDLR levels. These data confirm that PCSK9 reduces CD81 levels via an intracellular pathway as reported for LDLR. Using immunocytochemistry, a proximity ligation assay, and co-immunoprecipitation, we found that the cell surface level of PCSK9 was enhanced upon overexpression of CD81 and that both PCSK9 and LDLR interact with this tetraspanin protein. Interestingly, using CHO-A7 cells lacking LDLR expression, we revealed that LDLR was not required for the degradation of CD81 by PCSK9, but its presence strengthened the PCSK9 effect.     

Grassland ecosystems in China: review of current knowledge and research advancement

Grasslands are the dominant landscape in China, accounting for 40% of the national land area. Research concerning China's grassland ecosystems can be chronologically summarized into four periods: (i) pre-1950s, preliminary research and survey of grassland vegetation and plant species by Russians, Japanese and Western Europeans, (ii) 1950-1975, exploration and survey of vegetation, soils and topography as part of natural resource inventory programmes by regional and national institutions mainly led by the Chinese Academy of Sciences, (iii) 1976-1995, establishment of field stations for long-term ecological monitoring and studies of ecosystem processes, (iv) 1996-present, comprehensive studies of community dynamics and ecosystem function integrating multi-scale and multidisciplinary approaches and experimental manipulations.Major findings of scientific significance in China's grassland ecosystem research include: (i) improved knowledge on succession and biogeochemistry of the semi-arid and temperate grassland ecosystems, (ii) elucidation of life-history strategies and diapause characteristics of the native grasshopper species as one of the key grassland pests, and (iii) development of effective management strategies for controlling rodent pests in grassland ecosystems. Opportunities exist for using the natural grasslands in northern China as a model system to test ecosystem theories that so far have proven a challenge to ecologists worldwide.     

Phenome-Wide Association Studies on a Quantitative Trait: Application to TPMT Enzyme Activity and Thiopurine Therapy in Pharmacogenomics

Phenome-Wide Association Studies (PheWAS) investigate whether genetic polymorphisms associated with a phenotype are also associated with other diagnoses. In this study, we have developed new methods to perform a PheWAS based on ICD-10 codes and biological test results, and to use a quantitative trait as the selection criterion. We tested our approach on thiopurine S-methyltransferase (TPMT) activity in patients treated by thiopurine drugs. We developed 2 aggregation methods for the ICD-10 codes: an ICD-10 hierarchy and a mapping to existing ICD-9-CM based PheWAS codes. Eleven biological test results were also analyzed using discretization algorithms. We applied these methods in patients having a TPMT activity assessment from the clinical data warehouse of a French academic hospital between January 2000 and July 2013. Data after initiation of thiopurine treatment were analyzed and patient groups were compared according to their TPMT activity level. A total of 442 patient records were analyzed representing 10,252 ICD-10 codes and 72,711 biological test results. The results from the ICD-9-CM based PheWAS codes and ICD-10 hierarchy codes were concordant. Cross-validation with the biological test results allowed us to validate the ICD phenotypes. Iron-deficiency anemia and diabetes mellitus were associated with a very high TPMT activity (p = 0.0004 and p = 0.0015, respectively). We describe here an original method to perform PheWAS on a quantitative trait using both ICD-10 diagnosis codes and biological test results to identify associated phenotypes. In the field of pharmacogenomics, PheWAS allow for the identification of new subgroups of patients who require personalized clinical and therapeutic management.     

A halotolerant and thermotolerant <Emphasis Type="Italic">Bacillus</Emphasis> sp. degrades hydrocarbons and produces tensio-active emulsifying agent

A Bacillus sp. strain DHT, isolated from oil-contaminated soil, grew and produced biosurfactant when cultured in variety of substrate at salinities of up to 100 g l⁻¹ and temperatures up to 45°C. It was capable of utilizing crude oil, fuels, various pure alkanes and PAHs as a sole carbon and energy source across a wide range of temperature and salinity. Over the range evaluated, the degradation of hydrocarbon and biosurfactant production was not influenced by salinity (0–10% wv⁻¹) and temperature (30–45°C). The biosurfactant produced by the organism emulsified a range of hydrocarbons with hexadecane as the best substrate and toluene as the poorest. From 16S rDNA analysis, strain DHT was related to Bacillus licheniformis.     

High interleukin-4 expression and interleukin-4 gene polymorphisms are associated with susceptibility to human paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is caused by dimorphic fungi fromtheParacoccidioides brasiliensis complex. Previous studies havedemonstrated that the severity of disease is associated with a T-helper 2 immuneresponse characterised by high interleukin (IL)-4 production. In the present study weanalysed two polymorphisms in the IL-4 gene (-590 C/T and intron-3microsatellite) in 76 patients with PCM and 73 control subjects from an endemic area.The production of IL-4 by peripheral blood mononuclear cells after antigen orphytohaemagglutinin stimulation was determined by ELISA. A significant correlationwas observed between the RP2/RP2 intron-3 genotype and infection withParacoccidioides sp. (p = 0.011), whereas the RP1/RP1 genotypewas correlated with resistance. No significant correlation was observed forthe IL-4 promoter polymorphism. Furthermore, the low IL-4expression observed in the control group compared with patients was associated withthe RP1/RP1 genotype. These results suggest that IL-4polymorphismsmight be associated with the ability of the host to control Paracoccidioidessp. infection. The relevance of this polymorphism is supported by theobservation that patients with disease produce high levels of IL-4 following mitogenor antigen stimulation. The IL-4 gene is located in the cytokinecluster region of chromosome 5 where other polymorphisms have also beendescribed.     

Bacterial colonization of a fumigated alkaline saline soil

After chloroform fumigating an arable soil, the relative abundance of phylotypes belonging to only two phyla (Actinobacteria and Firmicutes) and two orders [Actinomycetales and Bacillales (mostly Bacillus)] increased in a subsequent aerobic incubation, while it decreased for a wide range of bacterial groups. It remained to be seen if similar bacterial groups were affected when an extreme alkaline saline soil was fumigated. Soil with electrolytic conductivity between 139 and 157 dS m^?1, and pH 10.0 and 10.3 was fumigated and the bacterial community structure determined after 0, 1, 5 and 10 days by analysis of the 16S rRNA gene, while an unfumigated soil served as control. The relative abundance of the Firmicutes increased in the fumigated soil (52.8 %) compared to the unfumigated soil (34.2 %), while that of the Bacteroidetes decreased from 16.2 % in the unfumigated soil to 8.8 % in the fumigated soil. Fumigation increased the relative abundance of the genus Bacillus from 14.7 % in the unfumigated soil to 25.7 %. It was found that phylotypes belonging to the Firmicutes, mostly of the genus Bacillus, were dominant in colonizing the fumigated alkaline saline as found in the arable soil, while the relative abundance of a wide range of bacterial groups decreased.