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

Calreticulin mutations affect its chaperone function and perturb the glycoproteome

Calreticulin (CALR) is an endoplasmic reticulum (ER)-retained chaperone that assists glycoproteins in obtaining their structure. CALR mutations occur in patients with myeloproliferative neoplasms (MPNs), and the ER retention of CALR mutants (CALR MUT) is reduced due to a lacking KDEL sequence. Here, we investigate the impact of CALR mutations on protein structure and protein levels in MPNs by subjecting primary patient samples and CALR-mutated cell lines to limited proteolysis-coupled mass spectrometry (LiP-MS). Especially glycoproteins are differentially expressed and undergo profound structural alterations in granulocytes and cell lines with homozygous, but not with heterozygous, CALR mutations. Furthermore, homozygous CALR mutations and loss of CALR equally perturb glycoprotein integrity, suggesting that loss-of-function attributes of mutated CALR chaperones (CALR MUT) lead to glycoprotein maturation defects. Finally, by investigating the misfolding of the CALR glycoprotein client myeloperoxidase (MPO), we provide molecular proof of protein misfolding in the presence of homozygous CALR mutations. Keywords: CP: Cancer; CP: Molecular biology; calreticulin; chaperone; glycoprotein; limited proteolysis-coupled mass spectrometry; myeloperoxidase; myeloproliferative neoplasm; protein folding; proteome

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

The prion-like RNA-processing protein HNRPDL forms inherently toxic amyloid-like inclusion bodies in bacteria

BACKGROUND: The formation of protein inclusions is connected to the onset of many human diseases. Human RNA binding proteins containing intrinsically disordered regions with an amino acid composition resembling those of yeast prion domains, like TDP-43 or FUS, are being found to aggregate in different neurodegenerative disorders. The structure of the intracellular inclusions formed by these proteins is still unclear and whether these deposits have an amyloid nature or not is a matter of debate. Recently, the aggregation of TDP-43 has been modelled in bacteria, showing that TDP-43 inclusion bodies (IBs) are amorphous but intrinsically neurotoxic. This observation raises the question of whether it is indeed the lack of an ordered structure in these human prion-like protein aggregates the underlying cause of their toxicity in different pathological states. RESULTS: Here we characterize the IBs formed by the human prion-like RNA-processing protein HNRPDL. HNRPDL is linked to the development of limb-girdle muscular dystrophy 1G and shares domain architecture with TDP-43. We show that HNRPDL IBs display characteristic amyloid hallmarks, since these aggregates bind to amyloid dyes in vitro and inside the cell, they are enriched in intermolecular β-sheet conformation and contain inner amyloid-like fibrillar structure. In addition, despite their ordered structure, HNRPDL IBs are highly neurotoxic. CONCLUSIONS: Our results suggest that at least some of the disorders caused by the aggregation of human prion-like proteins would rely on the formation of classical amyloid assemblies rather than being caused by amorphous aggregates. They also illustrate the power of microbial cell factories to model amyloid aggregation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-015-0284-7) contains supplementary material, which is available to authorized users

[The role of calcium in the effect of stress hormones].

During administration of stressogenic substances an increased shift of calcium ions into smooth muscles of the aorta and heart muscle takes place. Administration of a high-fat diet supplemented by cholesterol enhances this process. The calcium blood level does not change significantly during this procedure. The amount of calcium in bones declined after administration of stresso-genic hormones although the values were not statistically significant. It may be assumed that calcium ions shifted into the cardiovascular system originate from osseous tissue. Calcium accumulation during repeated or prolonged stress contributes towards the interpretation of the mechanism of action of stressogenic substances on the cardiovascular system. The increased supply of calcium ions into the heart muscle and coronary arteries may influence also the development of ischaemic heart disease and cardiomyopathies. The increased amount of calcium ions in smooth muscles of the aorta after prolonged administration of stressogenic substances indicates a higher content of calcium ions also in smooth muscle cells of arterioles which leads to a higher peripheral vascular tension. Stress alone does not lead to the development of atherosclerosis but creates favourable conditions for its development

Morpho-physiological characteristics and classification of the Chievitz' juxtaoral organ.

The authors suppose that thè parenchymal cells of thè Ist type of thè Chievitz' Juxtaoral organ may be paraneurons with respect to their secretory function which may modulate thè afferent dendritic zones of different kinds of sensory nerve fonnations — SNF (endings). In this respect thè parenchymal cells of thè Ist type may have thè same functions as glomus cells in thè glomus caroticum or Merkel cells in thè epidermis. As to thè function of thè Juxtaoral organ thè authors presume its multimodal mechanosensory function, as it contains 4 to 5 kinds of SNF (intraepithelial nerve fibers, simple arborizations, maybe Ruffini SNF, glomerular SNF, and simple sensory corpuscles) with 2 basic different modes of adaptation: simple SNF. and Ruffini SNF adapt slowly, some intraepithelial nerve fibers, glomerular SNF and lamellar corpuscles adapt rapidly. The existence of this organ already in newbom indicates its important mechanosensory function connected with nutrition reflexes and orai cavity walls tonus regulation, later on, connected with mastication and speech, too. As to thè classification, thè Juxtaoral organ belongs to complex SNF with a Constant accumulation of different kinds of SNF

Structural properties of poly-Si thin films grown on ZnO:Al coated glass substrates by aluminium induced crystallisation

International audienceThe structural properties of poly-Si thin films on ZnO:Al coated glass substrates obtained by Aluminium-Induced Crystallisation (AIC) in different annealing atmospheres - air, N2, and N2 + H2, have been studied by Raman microprobe spectroscopy, optical microscopy , and X-ray diffraction . The Al, ZnO:Al and a-Si films were deposited by r.f. magnetron sputtering. Annealing in forming gas led to a better structural quality of the poly-Si films, compared to annealing in air or nitrogen. The investigation of different annealing conditions in forming gas led to the conclusion that the two-step annealing technique provided AIC poly-Si films with better crystalline properties. The results indicated that the process of AIC is suitable for the preparation of poly-Si films on ZnO:Al coated glass substrates, for solar cell applications