Utilization of cyanide as nitrogenous substrate by Pseudomonas fluorescens NCIMB 11764: evidence for multiple pathways of metabolic conversion.

The growth of Pseudomonas fluorescens NCIMB 11764 on cyanide as the sole nitrogen source was accomplished by use of a modified fed-batch cultivation procedure. Previous studies showing that cyanide metabolism in this organism is both an oxygen-dependent and an inducible process, with CO2 and ammonia representing conversion products, were confirmed. However, washed cells (40 mg ml-1 [dry weight]) metabolized cyanide at concentrations far exceeding those previously described; 85% of 50 mM KCN was degraded in 6 h. In addition, two other C1 metabolites were detected in incubation mixtures; their identities were confirmed as formamide and formate by 13C nuclear magnetic resonance spectrocopy, high-pressure liquid chromatography, radioisotopic trapping experiments, and other analytical means. The relative yields of all four metabolites (CO2, formamide, formate, and ammonia) were shown to be dependent on the KCN concentration and availability of oxygen; at 0.5 to 10 mM substrate, CO2 was the major C1 product, whereas at 20 and 50 mM substrate, formamide and formate were principally formed. The latter two metabolites also accumulated during prolonged anaerobic incubation, suggesting that P. fluorescens NCIMB 11764 can elaborate several pathways of cyanide conversion. One is formally similar to that proposed previously (R. E. Harris and C. J. Knowles, FEMS Microbiol. Lett. 20:337-341, 1983), involving the oxygen-dependent conversion of cyanide to CO2 and ammonia. The other two, occurring in the presence or absence of oxygen, involve separate reactions to yield, respectively, formate plus ammonia or formamide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism

Autism is a common neurodevelopmental disorder with a significant genetic component. Existing research suggests that multiple genes contribute to autism and that epigenetic effects or gene-gene interactions are likely contributors to autism risk. However, these effects have not yet been identified. Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, has been implicated in autism etiology. Fourteen known autosomal GABA receptor subunit genes were studied to look for the genes associated with autism and their possible interactions. Single-nucleotide polymorphisms (SNPs) were screened in the following genes: GABRG1, GABRA2, GABRA4, and GABRB1 on chromosome 4p12; GABRB2, GABRA6, GABRA1, GABRG2, and GABRP on 5q34-q35.1; GABRR1 and GABRR2 on 6q15; and GABRA5, GABRB3, and GABRG3 on 15q12. Intronic and/or silent mutation SNPs within each gene were analyzed in 470 white families with autism. Initially, SNPs were used in a family-based study for allelic association analysis--with the pedigree disequilibrium test and the family-based association test--and for genotypic and haplotypic association analysis--with the genotype-pedigree disequilibrium test (geno-PDT), the association in the presence of linkage (APL) test, and the haplotype family-based association test. Next, with the use of five refined independent marker sets, extended multifactor-dimensionality reduction (EMDR) analysis was employed to identify the models with locus joint effects, and interaction was further verified by conditional logistic regression. Significant allelic association was found for markers RS1912960 (in GABRA4; P = .01) and HCV9866022 (in GABRR2; P = .04). The geno-PDT found significant genotypic association for HCV8262334 (in GABRA2), RS1912960 and RS2280073 (in GABRA4), and RS2617503 and RS12187676 (in GABRB2). Consistent with the allelic and genotypic association results, EMDR confirmed the main effect at RS1912960 (in GABRA4). EMDR also identified a significant two-locus gene-gene effect model involving RS1912960 in GABRA4 and RS2351299 in GABRB1. Further support for this two-locus model came from both the multilocus geno-PDT and the APL test, which indicated a common genotype and haplotype combination positively associated with disease. Finally, these results were also consistent with the results from the conditional logistic regression, which confirmed the interaction between GABRA4 and GABRB1 (odds ratio = 2.9 for interaction term; P = .002). Through the convergence of all analyses, we conclude that GABRA4 is involved in the etiology of autism and potentially increases autism risk through interaction with GABRB1. These results support the hypothesis that GABA receptor subunit genes are involved in autism, most likely via complex gene-gene interactions.     

Histones in crenarchaea

Archaeal histone-encoding genes have been identified in marine Crenarchaea. The protein encoded by a representative of these genes, synthesized in vitro and expressed in Escherichia coli, binds DNA and forms complexes with properties typical of an archaeal histone. The discovery of histones in Crenarchaea supports the argument that histones evolved before the divergence of Archaea and Eukarya.     

Vulnerability of the global terrestrial ecosystems to climate change

Climate change has far‐reaching impacts on ecosystems. Recent attempts to quantify such impacts focus on measuring exposure to climate change but largely ignore ecosystem resistance and resilience, which may also affect the vulnerability outcomes. In this study, the relative vulnerability of global terrestrial ecosystems to short‐term climate variability was assessed by simultaneously integrating exposure, sensitivity, and resilience at a high spatial resolution (0.05°). The results show that vulnerable areas are currently distributed primarily in plains. Responses to climate change vary among ecosystems and deserts and xeric shrublands are the most vulnerable biomes. Global vulnerability patterns are determined largely by exposure, while ecosystem sensitivity and resilience may exacerbate or alleviate external climate pressures at local scales; there is a highly significant negative correlation between exposure and sensitivity. Globally, 61.31% of the terrestrial vegetated area is capable of mitigating climate change impacts and those areas are concentrated in polar regions, boreal forests, tropical rainforests, and intact forests. Under current sensitivity and resilience conditions, vulnerable areas are projected to develop in high Northern Hemisphere latitudes in the future. The results suggest that integrating all three aspects of vulnerability (exposure, sensitivity, and resilience) may offer more comprehensive and spatially explicit adaptation strategies to reduce the impacts of climate change on terrestrial ecosystems.     

Mouse macrophage specific knockout of SIRT1 influences macrophage polarization and promotes angiotensin Ⅱ-induced abdominal aortic aneurysm formation

Abdominal aortic aneurysm (AAA) is a vascular degenerative disease. Macrophage polarization and the balance between classically activated macrophages (M1) and alternatively activated macrophages (M2) are crucial for AAA pathogenesis. The present study aims to investigate the roles of macrophage SIRT1 in AAA formation and macrophage polarization. We found that in mouse peritoneal macrophages, SIRT1 expression was decreased after M1 stimulation, but was enhanced after M2 stimulation. Results from SIRT1^flox/flox mice and macrophage specific SIRT1 knockout mice with treatment of angiotensin II (Ang II) for 4 weeks showed that macrophage specific deficiency of SIRT1 increased the incidence of AAA and exacerbated the severity, including more severe aneurysm types, enlarged diameter of the aneurysm and increased degradation of elastin. In mouse aortas, SIRT1 deficiency increased the pro-inflammatory M1 molecule inducible nitric oxide synthase (iNOS), and decreased M2 molecules such as arginase 1 (Arg1) and mannose receptor (MR). Furthermore, in peritoneal macrophages, SIRT1 deficiency increased the expression of M1 inflammatory molecules, but decreased the expression of M2 molecules. Overexpression of SIRT1 had the opposite effects. Thus, macrophage specific knockout of SIRT1 influences macrophage polarization and accelerates Ang II-induced AAA formation.     

生物冶金过程中的关键微生物及其碳循环代谢途径研究

【目的】深入研究极端酸性环境中微生物的碳循环过程。【方法】应用16S r RNA高通量测序和功能基因芯片技术对德兴铜矿中浸矿堆(LH)和积液池(LS)两个子系统中的微生物群落结构组成和功能基因组成进行分析;并运用PICRUSt功能基因预测的方法对群落功能进行预测。【结果】功能基因芯片和功能预测分析都表明碳循环基因在子系统间存在显著差异(P0.05),且碳固定相关的卡尔文循环、还原性三羧酸循环等基因以及碳降解相关的己聚糖和纤维素等基因在LS系统中都要明显高于LH系统。碳循环功能基因在子系统之间的差异与环境条件相关,其中TON、Ca、ES、Fe3+和P作用显著。【结论】在极端酸性环境中,环境条件的差异会对微生物群落碳循环功能基因产生筛选作用,参与碳循环的微生物的种类和相对丰度都发生变化,最终改变了群落碳循环模式。     

Proceedings of the 2016 China Cancer Immunotherapy Workshop

A1 Proceedings of 2016 China Cancer Immunotherapy Workshop, Beijing, China Bin Xue, Jiaqi Xu, Wenru Song, Zhimin Yang, Ke Liu, Zihai Li A2 Set the stage: fundamental immunology in forty minutes Zihai Li A3 What have we learnt from the anti-PD-1/PD-L1 therapy of advanced human cancer? Lieping Chen A4 Immune checkpoint inhibitors in lung cancer Edward B. Garon A5 Mechanisms of response and resistance to checkpoint inhibitors in melanoma Siwen Hu-Lieskovan A6 Checkpoint inhibitor immunotherapy in lymphoid malignancies Wei Ding A7 Translational research to improve the efficacy of immunotherapy in genitourinary malignancies Chong-Xian Pan A8 Immune checkpoint inhibitors in gastrointestinal malignancies Weijing Sun A9 What’s next beyond PD-1/PDL1? Yong-Jun Liu A10 Cancer vaccines: new insights into the oldest immunotherapy strategy Lei Zheng A11 Bispecific antibodies for cancer immunotherapy Delong Liu A12 Updates on CAR-T immunotherapy Michel Sadelain A13 Adoptive T cell therapy: personalizing cancer treatment Cassian Yee A14 Immune targets and neoantigens for cancer immunotherapy Rongfu Wang A15 Phase I/IIa trial of chimeric antigen receptor modified T cells against CD133 in patients with advanced and metastatic solid tumors Meixia Chen, Yao Wang, Zhiqiang Wu, Hanren Dai, Can Luo, Yang Liu, Chuan Tong, Yelei Guo, Qingming Yang, Weidong Han A16 Cancer immunotherapy biomarkers: progress and issues Lisa H. Butterfield A17 Shaping of immunotherapy response by cancer genomes Timothy A. Chan A18 Unique development consideration for cancer immunotherapy Wenru Song A19 Immunotherapy combination Ruirong Yuan A20 Immunotherapy combination with radiotherapy Bo Lu A21 Cancer immunotherapy: past, present and future Ke Liu A22 Breakthrough therapy designation drug development and approval Max Ning A23 Current European regulation of innovative oncology medicines: opportunities for immunotherapy Harald Enzmann, Heinz Zwierzina     

Physiological Characteristics and Leaf Ultrastructure of a Novel Chlorophyll-deficient chd6 Mutant of Vitis venifera Cultured in vitro

A novel chlorophyll-deficient chd6 mutant of F₁ hybrids from Vitis venifera was selected to study its primarily physiological characteristics and leaf ultrastructures under culturing in vitro. The results showed that although increasing Fe²⁺ and Mg²⁺ concentration could improve growth of the mutant in vitro, the effect was limited. In addition, it was determined that relatively lower Fe²⁺ and Mg²⁺ concentrations would be beneficial to the survival in vitro on GS medium. Chlorophyll contents of the mutant were significantly lower than those of its parents (4.53–13.76% of those of the higher-value parent Red globe). The chlorophyll a/b ratio was greatly increased (up to 4.34) to approximately twofold greater than that of its parents. Some critically successive enzymes for converting ALA to chlorophyll a could be inhibited to a variable extent in the chd6 mutant, and more serious inhibition could happen in critical enzymes converting Mg-proto to Pchlide or Mg-proto to chlorophyll b. The mutant also showed not only poor Rubisco activities, lower percentage of dry matter, and soluble carbohydrate content, but also lower IAA and GA (GA₁ + GA₄) content and higher ABA content. In leaf ultrastructures, the mutant presented larger stomata size, higher percentages of stomata opening, and lower stomata density with more stoma approximately a ring shape. Most chloroplasts of the chd6 mutant developed as asymmetric ellipses with deficient and irregular lamella.     

Neural Associations of the Early Retinotopic Cortex with the Lateral Occipital Complex during Visual Perception

Previous studies have demonstrated that the early retinotopic cortex (ERC, i.e., V1/V2/V3) is highly associated with the lateral occipital complex (LOC) during visual perception. However, it remains largely unclear how to evaluate their associations in quantitative way. The present study tried to apply a multivariate pattern analysis (MVPA) to quantify the neural activity in ERC and its association with that of the LOC when participants saw visual images. To this end, we assessed whether low-level visual features (Gabor features) could predict the neural activity in the ERC and LOC according to a voxel-based encoding model (VBEM), and then quantified the association of the neural activity between these regions by using an analogical VBEM. We found that the Gabor features remarkably predicted the activity of the ERC (e.g., the predicted accuracy was 52.5% for a participant) instead of that of the LOC (4.2%). Moreover, the MVPA approach can also be used to establish corresponding relationships between the activity patterns in the LOC and those in the ERC (64.2%). In particular, we found that the integration of the Gabor features and LOC visual information could dramatically improve the ‘prediction’ of ERC activity (88.3%). Overall, the present study provides new evidences for the possibility of quantifying the association of the neural activity between the regions of ERC and LOC. This approach will help to provide further insights into the neural substrates of the visual processing.