Steering Transplant Immunosuppression by Measuring Virus-Specific T Cell Levels: The Randomized,Controlled IVIST Trial

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Implication of Glycerol and Phospholipid Transporters in Mycoplasma pneumoniae Growth and Virulence

Mycoplasma pneumoniae, the causative agent of atypical pneumonia, is one of the bacteria with the smallest genomes that are nonetheless capable of independent life. Because of their longstanding close association with their human host, the bacteria have undergone reductive evolution and lost most biosynthetic abilities. Therefore, they depend on nutrients provided by the host that have to be taken up by the cell. Indeed, M. pneumoniae has a large set of hitherto unexplored transporters and lipoproteins that may be implicated in transport processes. Together, these proteins account for about 17% of the protein complement of M. pneumoniae. In the natural habitat of M. pneumoniae, human lung epithelial surfaces, phospholipids are the major available carbon source. Thus, the uptake and utilization of glycerol and glycerophosphodiesters that are generated by the activity of lipases are important for the nutrition of M. pneumoniae in its common habitat. In this study, we have investigated the roles of several potential transport proteins and lipoproteins in the utilization of glycerol and glycerophosphodiesters. On the basis of experiments with the corresponding mutant strains, our results demonstrate that the newly identified GlpU transport protein (MPN421) is responsible for the uptake of the glycerophosphodiester glycerophosphocholine, which is then intracellularly cleaved to glycerol-3-phosphate and choline. In addition, the proteins MPN076 and MPN077 are accessory factors in glycerophosphocholine uptake. Moreover, the lipoproteins MPN133 and MPN284 are essential for the uptake of glycerol. Our data suggest that they may act as binding proteins for glycerol and deliver glycerol molecules to the glycerol facilitator GlpF.     

Do programmed death 1 (PD-1) and its ligand (PD-L1) play a role in patients with non-clear cell renal cell carcinoma?

Clinical trials targeting programmed death 1 (PD-1) and its ligand PD-L1 (PD-L1) for metastatic renal cell cancer (RCC) are ongoing. The aim of this study is to validate their roles as prognostic markers in non-clear cell (non-cc) RCC. Sixty-four non-cc RCC tissue specimens were collected from patients undergoing renal tumor surgery. Expressions of biomarkers were assessed using immunohistochemistry and compared with clinical characteristics. Survival analyses were performed with a median follow-up of 77.5 (range: 0–176) months. No significant correlations were found for PD-1⁺ tumor-infiltrating mononuclear cells (TIMC) or PD-L1⁺ expression and clinical attributes in patients with non-cc RCC. Kaplan–Meier analysis revealed no differences in 5- and 10-year cancer-specific survival (CSS) for PD-1^? TIMC compared to PD-1⁺ TIMC (71.4 and 63 % versus 72.2 and 61.9 %; p = 0.88). Intratumoral expression of PD-L1 did not appear to influence the 5- and 10-year CSS significantly, even though a trend was identified (68 and 53.6 % versus 80.1 and 75.7 %; p = 0.08). In multivariate analysis, neither PD-1⁺ TIMC nor intratumoral PD-L1⁺ expression proved to be independent predictors of CSS (p = 0.99 and p = 0.68, respectively). Our study demonstrates that PD-1⁺ TIMC and intratumoral PD-L1⁺ expression did not significantly impact tumor aggressiveness or clinical outcome in non-ccRCC specimens. Due to rare incidence of non-cc RCC in particular according to PD-L1 expression, further analyzes are warranted.