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Aims: Total haemoglobin mass (tot-Hb) increases during high-altitude acclimatization. Normalization of tot-Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m). Methods: Newly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19-day high-altitude sojourn by ingestion of 13C2-and 15N-labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot-Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling. Results: Tot-Hb increased by 4.7% ± 2.7% at high altitude and returned to pre-altitude values within 11 days after descent. Elimination of 13C-(normoxia) and 15N-(high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71-positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3-4 days after descent and normalized slowly. There was no indication of haemolysis. Conclusion: We confirm a rapid normalization of tot-Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes. [ABSTRACT FROM AUTHOR]

The time-course of changes in labelling of reticulocytes with Mito-tracker and Mito-Sox indicate, although the time-course of change does not exactly match, that mitochondria may be present for a prolonged time in hypoxia-born erythrocytes. Of mice and men1: How to achieve a better life with lower total Hb mass after returning from hypoxia to normoxia. Song and colleagues3 argue that the reactive oxygen species (ROS) thought to destroy the erythrocytes might come from erythrocytic mitochondria, indicated by mitochondrial markers. [Extracted from the article]

l-methionine ( l-Met) is the only sulphur-containing proteinogenic amino acid together with cysteine. Its importance is highlighted by it being the initiator amino acid for protein synthesis in all known living organisms. l-Met, free or inserted into proteins, is sensitive to oxidation of its sulfide moiety, with formation of l-Met sulfoxide. The sulfoxide could not be inserted into proteins, and the oxidation of l-Met in proteins often leads to the loss of biological activity of the affected molecule. Key discoveries revealed the existence, in rats, of a metabolic pathway for the reduction of free l-Met sulfoxide and, later, in Escherichia coli, of the enzymatic reduction of l-Met sulfoxide inserted in proteins. Upon oxidation, the sulphur atom becomes a new stereogenic center, and two stable diastereoisomers of l-Met sulfoxide exist. A fundamental discovery revealed the existence of two unrelated families of enzymes, MsrA and MsrB, whose members display opposite stereospecificity of reduction for the two sulfoxides. The importance of Msrs is additionally emphasized by the discovery that one of the only 25 selenoproteins expressed in humans is a Msr. The milestones on the road that led to the discovery and characterization of this group of antioxidant enzymes are recounted in this review. © 2015 BioFactors, 41(3):135-152, 2015 [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy ( BNCT) is an anticancer treatment based on the accumulation in the tumor cells of 10 B-containing molecules and subsequent irradiation with low-energy neutrons, which bring about the decay of 10 B to very toxic 7 Li3+ and 4 He2+ ions. The effectiveness of BNCT is limited by the low delivery and accumulation of the used 10 B-containing compounds. Here, we report the development of folic acid-conjugated 4-amino-phenylboronate as a novel possible compound for the selective delivery of 10 B in BNCT. An extensive analysis about its biocompatibility to mature blood cells and platelet progenitors revealed that the compound markedly supports platelet aggregation, neutrophil oxidative burst, and inhibition of megakaryocyte development, while it does not have any manifest effect on red blood cells. [ABSTRACT FROM AUTHOR]

ZO-1 is a peripheral protein that plays a central role in the macromolecular assembly of tight junctions by interacting with integral proteins (occludin, claudins, JAMs) of the membrane of adjoining cells, with the actin cytoskeleton, and with nuclear factors. Human ZO-1 is expressed in all epithelia and some specialized endothelia as variable amounts of two related isoforms, which originate from the alternatively spliced mRNA transcripts α+ and α− and whose specific differential role is still unknown. Moreover, little is known about the timing of expression of ZO-1 isoforms at the protein and mRNA level. This study shows that during growth of freshly plated Caco-2 cells, the α+/α− ratio increased as a result of simultaneous increase of α+ and decrease of α−. Differences in the isoform ratio also correlated with differences in epithelium differentiation. This was determined by aminopeptidase N measurements of cells grown on conventional substrates and on modified, micro/nano-patterned surfaces. A comparable shift of ZO-1 isoforms was not observed in other tumour cell lines of non-intestinal origin (A549, Calu-3). Pancreatic stem cells, propagated without exogenous differentiation stimuli, displayed a slight, stable prevalence of the α− isoform. Of the intestinal cell lines examined (Caco-2 and T84), only Caco-2 cells displayed a dramatic shift in isoform expression. This suggests that this tumour cell line retains to a higher degree a developmental programme related to the dynamic of enterocytic differentiation in vivo. [ABSTRACT FROM AUTHOR]