A novel acidification mechanism for greatly enhanced oxygen supply to the fish retina.

Previously, we showed that the evolution of high acuity vision in fishes was directly associated with their unique pH-sensitive hemoglobins that allow O to be delivered to the retina at POs more than ten-fold that of arterial blood (Damsgaard et al., 2019). Here, we show strong evidence that vacuolar-type H-ATPase and plasma-accessible carbonic anhydrase in the vascular structure supplying the retina act together to acidify the red blood cell leading to O secretion.

Retinal oxygen supply shaped the functional evolution of the vertebrate eye.

The retina has a very high energy demand but lacks an internal blood supply in most vertebrates. Here we explore the hypothesis that oxygen diffusion limited the evolution of retinal morphology by reconstructing the evolution of retinal thickness and the various mechanisms for retinal oxygen supply, including capillarization and acid-induced haemoglobin oxygen unloading. We show that a common ancestor of bony fishes likely had a thin retina without additional retinal oxygen supply mechanisms and that three different types of retinal capillaries were gained and lost independently multiple times during the radiation of vertebrates, and that these were invariably associated with parallel changes in retinal thickness.

Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies.

Background: Predicting metastasis in melanoma patients is important for disease management and could help to identify those who might benefit from adjuvant treatment. The aim of this study was to investigate whether the tumor microenvironment-derived protein S100A8/A9 qualifies as prognostic marker for melanoma patients, also in the setting of immunotherapy.

Methods: S100A8/A9 gene and protein expression were analyzed on melanocytic nevi, primary melanomas and metastases using a cDNA library and three independent tissue-microarrays (TMA).

Postmortem protein stability investigations of the human hepatic drug-metabolizing cytochrome P450 enzymes CYP1A2 and CYP3A4 using mass spectrometry.

Variability in expression and activity of hepatic drug-metabolizing cytochrome P450 (CYP) enzymes can play a causal role in fatal intoxication cases and is thus of forensic interest. We investigated the feasibility of LC-MS/MS based quantification and in vitro enzyme activity measurements of two major drug-metabolizing enzymes CYP1A2 and CYP3A4 in postmortem human liver microsomes (HLM). In autopsy cases (postmortem interval 24-36 h) we found CYP1A2 and CYP3A4 protein levels similar to that measured in a non-decayed reference HLM pool, whereas CYP1A2 and CYP3A4 enzyme activities were absent or severely decreased.

DNA and RNA analysis of blood and muscle from bodies with variable postmortem intervals.

The breakdown of DNA and RNA in decomposing human tissue represents a major obstacle for postmortem forensic molecular analysis. This study investigated the feasibility of performing PCR-based molecular analysis of blood and muscle tissue from 45 autopsy cases with defined postmortem intervals ranging from one to more than 14 days. It was not possible to collect blood from 38 % of the autopsy cases due to severe coagulation and hemolysis, whereas muscle tissue was available for all cases.