Evidence of a kallikrein inhibitor in human kidney. A new ring of the kallikrein-renin-angiotensin-aldosterone chain

By means of immunohistochemical reactions, the authors proved the inhibitor II-related immunoreactivity in distal convoluted tubules of human kidney. A sharp inhibitor II-related immunoreactivity was also present in the blood vessels' wall. On the contrary, in the wall of proximal tubules and glomeruli only low reactivity was found. The demonstration of an inhibitor II-related immunoreactivity in the distal convoluted tubules and vessels of human kidney represents a strong evidence that an inhibitor of kallikrein exists and acts also in humans as an important key in the kallikrein-renin-angiotensin aldosterone chain and hitherto confirms the experimental data of the literature. The proved inhibitor in the human kidney may intervene in the modulation of the kallikrein-kinin system and thus represents a key role in the intrarenal mechanisms related to the blood flow and arterial pressure regulation

Venous wall ultrastructure in generalized venomegaly.

The ultrastructure of thè v. colica sinistra in a case of generalized vasomegaìy in man was examined. Elastic material was found in three forms: as a lightly osmiophii amorphous material bordering on myocytes, as a highly osmiophii elastic membrana, and as highly osmiophii slim elastic fibres of different orientation in thè tunica media and adventitia. The slightly osmiophii elastic material is assumed to be newly formed. by pinocytotic activity of thè myocytes. The highly osmiophii elastic material indicatss its impairment. No typical atherosclerotic changes were found in thè examined vein. Based on a comparison with previous findings in thè case of vasomegaìy of thè a. mesenterica inferior, thè authors conclude that thè venomegaly phenomenon is connected with degenerative changes in thè elastic material of thè vessel wall

Fission Yeast Does Not Age under Favorable Conditions, but Does So after Stress

SummaryBackgroundMany unicellular organisms age: as time passes, they divide more slowly and ultimately die. In budding yeast, asymmetric segregation of cellular damage results in aging mother cells and rejuvenated daughters. We hypothesize that the organisms in which this asymmetry is lacking, or can be modulated, may not undergo aging.ResultsWe performed a complete pedigree analysis of microcolonies of the fission yeast Schizosaccharomyces pombe growing from a single cell. When cells were grown under favorable conditions, none of the lineages exhibited aging, which is defined as a consecutive increase in division time and increased death probability. Under favorable conditions, few cells died, and their death was random and sudden rather than following a gradual increase in division time. Cell death correlated with the inheritance of Hsp104-associated protein aggregates. After stress, the cells that inherited large aggregates aged, showing a consecutive increase in division time and an increased death probability. Their sisters, who inherited little or no aggregates, did not age.ConclusionsWe conclude that S. pombe does not age under favorable growth conditions, but does so under stress. This transition appears to be passive rather than active and results from the formation of a single large aggregate, which segregates asymmetrically at the subsequent cell division. We argue that this damage-induced asymmetric segregation has evolved to sacrifice some cells so that others may survive unscathed after severe environmental stresses

Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins