ABSTRACT
Better understanding how organisms respond to their abiotic environment, especially at the biochemical level, is critical in predicting population trajectories under climate change. In this study, we measured constitutive stress biomarkers and protein post-translational modifications associated with oxidative stress in Gallotia galloti, an insular lizard species inhabiting highly heterogeneous environments on Tenerife. Tenerife is a small volcanic island in a relatively isolated archipelago off the West coast of Africa. We found that expression of GRP94, a molecular chaperone protein, and levels of protein carbonylation, a marker of cellular stress, change across different environments, depending on solar radiation-related variables and topology. Here, we report in a wild animal population, cross-talk between the baseline levels of the heat shock protein-like GRP94 and oxidative damage (protein carbonylation), which are influenced by a range of available temperatures, quantified through modelled operative temperature. This suggests a dynamic trade-off between cellular homeostasis and oxidative damage in lizards adapted to this thermally and topologically heterogeneous environment.
Subject(s)
Heat-Shock Proteins , Lizards , Animals , Oxidative Stress , Protein Processing, Post-Translational , Protein CarbonylationABSTRACT
2020: annus horribilis for hospital medicine? The past year, notable because of the current pandemic, has had a profound impact on multiple aspects of medical practice. Just as all medical staff and the general population, hospital internists were put under immense strain in 2020. This year has more than ever reinforced our belief in the importance of keeping a critical and scientific eye on the mass of new studies and data produced every year. The internists of the HUG propose a critical review of selected recent publications that may influence our daily management of patients.
2020 : annus horribilis pour la médecine hospitalière ? L'année écoulée, marquée par la pandémie en cours, a eu un impact majeur sur de multiples aspects de notre pratique. Comme l'ensemble du monde médico-soignant et de la population, les internistes hospitaliers ont été mis à rude épreuve en 2020. Cette année a plus que jamais renforcé notre conviction de l'importance de porter un regard scientifique sur la masse de nouveautés qui surviennent chaque année. Les internistes hospitaliers des HUG vous proposent de partager leur vision critique de publications scientifiques récentes utiles pour notre pratique quotidienne.
Subject(s)
Internal Medicine , Hospitals , Humans , PhysiciansABSTRACT
Questions of reproducibility and efficacy of histologic malignancy grading relative to alternative proliferation index measurements for outcome prediction remain unanswered. Microsections of specimens from the Cooperative Breast Cancer Tissue Resource (CBCTR) were evaluated by seven pathologists for reproducibility of grade and classification. Nuclear figure classification was assessed using photographs. Grade was assigned by the Bloom-Richardson method, Nottingham modification. Proliferation index was evaluated prospectively by deoxyribose nucleic acid precursor uptake with thymidine (autoradiographic) or bromodeoxyuridine (immunohistochemical) labeling index using fresh tissue from 631 node-negative breast cancer patients accessioned at St Luke's Hospital. A modified Nottingham-Bloom-Richardson grade was derived from histopathologic data. Median post-treatment observation was 6.4 years. Agreement on classification of nuclear figures (N=43) was less than good by kappa statistic (kappa=0.38). Grade was moderately reproducible in four trials (N=10,10,19, 10) with CBCTR specimens (kappa=0.50-0.59). Of components of Bloom-Richardson grade, agreement was least for nuclear pleomorphism (kappa=0.37-0.50), best for tubularity (kappa=0.57-0.83), and intermediate for mitotic count (kappa=0.45-0.64). Bloom-Richardson grade was a univariate predictor of prognosis in node-negative St Luke's patients, and was improved when mitotic count was replaced by labeling index (low, mid, or high). When labeling index was added to a multivariate model containing tumor size and vessel invasion, grade was no longer a significant predictor of tumor-specific relapse-free or overall survival. Mitotic index predicted best when intervals were lowered to 0-2, 3-10, and >10 mitotic figures per ten 0.18 mm(2) high-power fields. We conclude that Nottingham-Bloom-Richardson grades remain only modestly reproducible. Prognostically useful components of grade are mitotic index and tubularity. The Nottingham-Bloom-Richardson system can be improved by lowering cutoffs for mitotic index and by counting 20-30 rather than 10 high-power fields. Measurement of proliferation index by immunohistochemically detectable markers will probably give superior prognostic results in comparison to grade.
