Project description:The multitude of obesogenic diets used in rodent studies can hardly be overviewed. Since standardization is missing and assuming that individual compositions provoke individual effects, the choice of quality, quantity and combination of diet ingredients seems to be crucial for the outcome and interpretation of obesity studies. Therefore, the present study was conducted to compare the individual effects of three commonly used obesogenic diets, mainly differing in sugar and fat content. Besides basic phenotypic and metabolic characterization, one main aspect was a comparative liver proteome analysis. As expected, the obtained results picture differentiated consequences mainly depending on fat source and/or fat- and sugar quantity. By confirming the general presumption that the choice of nutritional composition is a pivotal factor, the present findings demonstrate that a conscious selection is indispensable for obtaining reliable and sound results in obesity research. In conclusion, we strongly recommend a careful selection of the appropriate diet in advance of a new experiment, taking into account the specific research question.
Project description:Following a multivariant analysis we demonstrated that children and adolescents with Burkitt lymphoma (BL) and a 13q14.3 deletion have a significant decrease in event free survival (EFS) despite identical short intensive multi-agent chemotherapy. However, how this deletion in the 13q14.3 region is associated with a significant decrease in EFS in children and adolescents with BL is largely unknown. The gene Deleted in Lymphocytic Leukemia 1 (DLEU1) is located in the region of 13q14.3. Here, we report that DLEU1 expression is implicated in the regulation of BL programmed cell death, cell proliferation, and expression of apoptotic genes in transcription activator-like effector nuclease (TALEN)s-induced DLEU1 knockdown and DLEU1 overexpressing BL cell lines. Furthermore, NSG mice xenografted with DLEU1 knockdown BL cells had significantly shortened survival (p < 0.05 and p < 0.005), whereas those xenografted with DLEU1 overexpressing BL cells had significantly improved survival (p < 0.05 and p < 0.0001), following treatment with rituximab and/or cyclophosphamide. These data suggest that DLEU1 may in part function as a tumor suppressor gene and confer chemoimmunotherapy resistance in children and adolescents with BL.
Project description:Epstein-Barr virus (EBV) is present in all cases of endemic Burkitt lymphoma (BL) but in few European/North American sporadic BLs. Gene expression arrays of sporadic tumors have defined a consensus BL profile within which tumors are classifiable as "molecular BL" (mBL). Where endemic BLs fall relative to this profile remains unclear, since they not only carry EBV but also display one of two different forms of virus latency. Here, we use early-passage BL cell lines from different tumors, and BL subclones from a single tumor, to compare EBV-negative cells with EBV-positive cells displaying either classical latency I EBV infection (where EBNA1 is the only EBV antigen expressed from the wild-type EBV genome) or Wp-restricted latency (where an EBNA2 gene-deleted virus genome broadens antigen expression to include the EBNA3A, -3B, and -3C proteins and BHRF1). Expression arrays show that both types of endemic BL fall within the mBL classification. However, while EBV-negative and latency I BLs show overlapping profiles, Wp-restricted BLs form a distinct subgroup, characterized by a detectable downregulation of the germinal center (GC)-associated marker Bcl6 and upregulation of genes marking early plasmacytoid differentiation, notably IRF4 and BLIMP1. Importantly, these same changes can be induced in EBV-negative or latency I BL cells by infection with an EBNA2-knockout virus. Thus, we infer that the distinct gene profile of Wp-restricted BLs does not reflect differences in the identity of the tumor progenitor cell per se but differences imposed on a common progenitor by broadened EBV gene expression.
Project description:It is difficult to distinguish influx and efflux of inorganic C in photosynthesizing tissues; this article examines what is known and where there are gaps in knowledge. Irreversible decarboxylases produce CO2, and CO2 is the substrate/product of enzymes that act as carboxylases and decarboxylases. Some irreversible carboxylases use CO2; others use HCO3(-). The relative role of permeation through the lipid bilayer versus movement through CO2-selective membrane proteins in the downhill, non-energized, movement of CO2 is not clear. Passive permeation explains most CO2 entry, including terrestrial and aquatic organisms with C3 physiology and biochemistry, terrestrial C4 plants and all crassulacean acid metabolism (CAM) plants, as well as being part of some mechanisms of HCO3(-) use in CO2 concentrating mechanism (CCM) function, although further work is needed to test the mechanism in some cases. However, there is some evidence of active CO2 influx at the plasmalemma of algae. HCO3(-) active influx at the plasmalemma underlies all cyanobacterial and some algal CCMs. HCO3(-) can also enter some algal chloroplasts, probably as part of a CCM. The high intracellular CO2 and HCO3(-) pools consequent upon CCMs result in leakage involving CO2, and occasionally HCO3(-). Leakage from cyanobacterial and microalgal CCMs involves up to half, but sometimes more, of the gross inorganic C entering in the CCM; leakage from terrestrial C4 plants is lower in most environments. Little is known of leakage from other organisms with CCMs, though given the leakage better-examined organisms, leakage occurs and increases the energetic cost of net carbon assimilation.