Empirical evaluation of observation scale effects in community time series

Natural communities are highly complex and dynamic over time, with populations structured by numerous abiotic and biotic forces acting through direct and indirect pathways. Multispecies Autoregressive (MAR) modeling can be used to partition effects of variables that are interrelated and temporally autocorrelated in time series from natural systems. Here we address two main questions in applying MAR models to community time series. First, what is the effect of observation scale on interpretation of community dynamics? We used a 10‐year weekly planktonic time series from Lake Washington to construct multiple “biweekly” and “monthly” data sets, and compared resulting community interaction models. Direct abiotic effects and intraspecific autocorrelation were apparent using all data sets. Biotic interactions were more apparent using biweekly and monthly data, indicating that time lags longer than one week were necessary to detect numerical response to interspecific interactions. Second, we examined effects of dropping the winter months from our analyses to simulate the common practice of sampling only during the “growing season” in long‐term ecological studies. We found that biotic interactions remained similarly characterized in models using only non‐winter months, but that the importance of seasonal physical factors nearly disappeared in non‐winter models. Exclusion of winter data in sampling designs may therefore allow us to characterize biotic interactions, although it may not help us understand populations’ relationships to seasonal abiotic variables. The models supported many previous findings from experimental and qualitative investigations of Lake Washington community interactions, implying that MARs provided plausible characterizations of community dynamics, but some previously unconsidered relationships did emerge, such as the importance of cryptomonads and picoplankton for zooplankton growth. We conclude that explicit consideration of time lags in biotic response is necessary to understand relative importance of abiotic and biotic factors, and that sampling regime can therefore strongly influence our interpretations of community dynamics.     

A phosphoproteomic analysis of the ErbB2 receptor tyrosine kinase signaling pathways

Overexpression of the ErbB2 receptor tyrosine kinase is common in human cancers and is associated with an increased level of metastasis. To better understand the cellular signaling networks activated by ErbB2, a phosphoproteomic analysis of tyrosine-phosphorylated proteins was carried out in ErbB2-overexpressing breast and ovarian cancer cell lines. A total of 153 phosphorylation sites were assigned on 78 proteins. Treatment of cells with Herceptin, a monoclonal antibody that inhibits ErbB2 activity, significantly reduced the number of detectable protein phosphorylation sites, suggesting that many of these proteins participate in ErbB2-driven cell signaling. Of the 71 proteins that were differentially phosphorylated, only 13 were previously reported to directly associate with ErbB2. The differentially phosphorylated proteins included kinases, adaptor/docking proteins, proteins involved in cell proliferation and migration, and several uncharacterized RNA binding proteins. Selective depletion of some of these proteins, including RNA binding proteins SRRM2, SFRS1, SFRS9, and SFRS10, by siRNAs reduced the rate of migration of ErbB2-overexpressing ovarian cancer cells.     

ER stress response: getting the UPR hand on misfolded proteins

Unfolded proteins are constantly delivered to the ER lumen, where they must be removed by folding or degradation. Recent studies show that the 'unfolded protein response' controls essentially all aspects of ER function, coordinating these two fates for misfolded proteins in a process necessary for normal cell life.     

Cadmium exerts its toxic effects on photosynthesis via a cascade mechanism in the cyanobacterium,Synechocystis PCC 6803

Despite intense research, the mechanism of Cd²⁺ toxicity on photosynthesis is still elusive because of the multiplicity of the inhibitory effects and different barriers in plants. The quick Cd²⁺ uptake in Synechocystis PCC 6803 permits the direct interaction of cadmium with the photosynthetic machinery and allows the distinction between primary and secondary effects. We show that the CO₂‐dependent electron transport is rapidly inhibited upon exposing the cells to 40 µm Cd²⁺ (50% inhibition in ～15 min). However, during this time we observe only symptoms of photosystem I acceptor side limitation and a build of an excitation pressure on the reaction centres, as indicated by light‐induced P700 redox transients, O₂ polarography and changes in chlorophyll a fluorescence parameters. Inhibitory effects on photosystem II electron transport and the degradation of the reaction centre protein D1 can only be observed after several hours, and only in the light, as revealed by chlorophyll a fluorescence transients, thermoluminescence and immunoblotting. Despite the marked differences in the manifestations of these short‐ and long‐term effects, they exhibit virtually the same Cd²⁺ concentration dependence. These data strongly suggest a cascade mechanism of the toxic effect, with a primary effect in the dark reactions.     

Gene Expression Profile of Peripheral Blood Lymphocytes from Renal Cell Carcinoma Patients Treated with IL-2, Interferon-�� and Dendritic Cell Vaccine

Lymphocytes are a key component of the immune system and their differentiation and function are directly influenced by cancer. We examined peripheral blood lymphocyte (PBL) gene expression as a biomarker of illness and treatment effect using the Affymetrix Human Gene ST1 platform in patients with metastatic renal cell carcinoma (mRCC) who received combined treatment with IL-2, interferon-?-2a and dendritic cell vaccine. We examined gene expression, cytokine levels in patient serum and lymphocyte subsets as determined by flow cytometry (FCM). Pre-treatment PBLs from patients with mRCC exhibit a gene expression profile and serum cytokine profile consistent with inflammation and proliferation not found in healthy donors (HD). PBL gene expression from patients with mRCC showed increased mRNA of genes involved with T-cell and T_REG-cell activation pathways, which was also reflected in lymphocyte subset distribution. Overall, PBL gene expression post-treatment (POST) was not significantly different than pre-treatment (PRE). Nevertheless, treatment related changes in gene expression (post-treatment minus pre-treatment) revealed an increased expression of T-cell and B-cell receptor signaling pathways in responding (R) patients compared to non-responding (NR) patients. In addition, we observed down-regulation of T_REG-cell pathways post-treatment in R vs. NR patients. While exploratory in nature, this study supports the hypothesis that enhanced inflammatory cytotoxic pathways coupled with blunting of the regulatory pathways is necessary for effective anti-cancer activity associated with immune therapy. This type of analysis can potentially identify additional immune therapeutic targets in patients with mRCC.