Ant assemblages in intact big sagebrush and converted cheatgrass-dominated habitats in Tooele County, Utah

Biological invasions are one of the greatest threats to native species in natural ecological systems. One of the most successful invasive species is Bromus tectorum L. (cheatgrass), which is having marked impacts on native plant communities and ecosystem processes. However, we know little about the effects of this invasion on native animal species in the Intermountain West. Because ants have been used to detect ecological change associated with anthropogenic land use, they seem well suited for a preliminary evaluation of the consequences of cheatgrass-driven habitat conversion. In our study, we used pitfall traps to assess ant community assemblages in intact sagebrush and nearby cheatgrass-dominated vegetation. Ant abundance was about 10-fold greater in cheatgrass-dominated plots than in sagebrush plots. We also noted differences in diversity and evenness between habitat types at both the species and the functional-group levels of organization. At the species level, Shannon’s diversity index was greater in sagebrush plots than in cheatgrass-dominated plots. However, at the functional-group level, Simpson’s and Shannon’s diversity indices and the Brillouin evenness index were greater in cheatgrass-dominated plots than in sagebrush plots. Further, common species / functional groups tended to be more abundant while less common species / functional groups tended to be less abundant in cheatgrass-dominated plots compared to intact sagebrush plots. Patterns appear to be at least partially related to resource availabilities. This initial survey of ant communities from intact-native and altered vegetation types may be indicative of similar trends of biodiversity shifts throughout the Intermountain West where cheatgrass has successfully replaced native species. We also discuss the implications of ant communities on land management activities, specifically in the context of aridland restoration.     

Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma

G protein-coupled receptors (GPCRs), the largest human gene family, are important regulators of signaling pathways. However, knowledge of their genetic alterations is limited. In this study, we used exon capture and massively parallel sequencing methods to analyze the mutational status of 734 GPCRs in melanoma. This investigation revealed that one family member, GRM3, was frequently mutated and that one of its mutations clustered within one position. Biochemical analysis of GRM3 alterations revealed that mutant GRM3 selectively regulated the phosphorylation of MEK, leading to increased anchorage-independent growth and migration. Melanoma cells expressing mutant GRM3 had reduced cell growth and cellular migration after short hairpin RNA-mediated knockdown of GRM3 or treatment with a selective MEK inhibitor, AZD-6244, which is currently being used in phase 2 clinical trials. Our study yields the most comprehensive map of genetic alterations in the GPCR gene family.     

北京大气细粒子PM2.5的化学组成

为了解北京大气细粒子(PM2.5)的污染水平和污染特征,在车公庄和清华园进行了连续1年、每周1次同步采样和全样品分析。2个采样点PM2.5的化学组成相似。含碳组分和水溶性离子是主要的组分,其质量浓度之和超过PM2.5的50%。有机碳、元素碳和细粒子PM2.5的季节变化一致,即冬季质量浓度最高,夏季最低。夏季NO-3的质量浓度最低且在采样过程中从特氟隆滤膜上有近50%的挥发。SO2-4不同于PM2.5的季节变化主要取决于SO2的转化率。地壳元素的质量浓度从冬季到春季大幅度上升,春季沙尘天气频是一个重要原因。     

Selective killing of cancer cells by a small molecule targeting the stress response to ROS

Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells. Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress.     

Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation

Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR-3 expression and excessive sprouting, which was inhibited by blocking VEGFR-3 signals. Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors.