Sharing for Caring? A Patients' and Clinicians' View on Handling Personal Medical Data in the Context of Digitization: An Exploratory Study.

Background: The healthcare sector is currently undergoing a significant transformation, driven by an increased utilization of data. In this evolving landscape, surveys are of pivotal importance to the comprehension of patient needs and preferences. Moreover, the digital affinity of patients and physicians within the healthcare system is reforming the manner in which healthcare services are accessed and delivered.

Crystal structure analysis of free and substrate-bound 6-hydroxy-L-nicotine oxidase from Arthrobacter nicotinovorans.

The pathway for oxidative degradation of nicotine in Arthrobacter nicotinovorans includes two genetically and structurally unrelated flavoenzymes, 6-hydroxy-L-nicotine oxidase (6HLNO) and 6-hydroxy-D-nicotine oxidase, which act with absolute stereospecificity on the L- and D-forms, respectively, of 6-hydroxy-nicotine. We solved the crystal structure of 6HLNO at 1.95 A resolution by combined isomorphous/multiple-wavelength anomalous dispersion phasing.

Cellular abnormalities linked to endoplasmic reticulum dysfunction in cerebrovascular disease--therapeutic potential.

Unfolded proteins accumulate in the lumen of the endoplasmic reticulum (ER) as part of the cellular response to cerebral hypoxia/ischemia and also to the overexpression of the mutant genes responsible for familial forms of degenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyothrophic lateral sclerosis, and Huntington's disease, as well as other disorders that are caused by an expanded CAG repeat. This accumulation arises from an imbalance between the load of proteins that need to be folded and processed in the ER lumen and the ER folding/processing capacity. To withstand such potentially lethal conditions, stress responses are activated that includes the shutdown of translation to reduce the ER work load and the activation of the expression of genes coding for proteins involved in the folding and processing reactions, to increase folding/processing capacity.

Endoplasmic reticulum stress response and neurodegeneration.

The endoplasmic reticulum (ER) is a subcellular compartment playing a central role in calcium storage and signaling. Disturbances of ER calcium homeostasis constitute a severe form of stress interfering with central functions of this structure including the folding and processing of newly synthesized membrane and secretory proteins. Blocking the folding and processing reactions results in the accumulation of unfolded proteins forming potentially toxic aggregates.

Conditions associated with ER dysfunction activate homer 1a expression.

Homer proteins physically link metabotropic glutamate receptors with IP3 receptors located at the endoplasmic reticulum (ER) and thereby modulate receptor-activated calcium signaling. Homer 1a, the short form of constitutively expressed homer 1 proteins, exerts dominant negative activity with respect to homer 1 proteins by interfering with the formation of multiprotein complexes. Homer 1a is an immediate early gene, the expression of which is activated by various stimuli including glutamate receptor activation.

Transient cerebral ischemia activates processing of xbp1 messenger RNA indicative of endoplasmic reticulum stress.

Cells respond to conditions associated with endoplasmic reticulum (ER) dysfunction with activation of the unfolded protein response, characterized by a shutdown of translation and induction of the expression of genes coding for ER stress proteins. The genetic response is based on IRE1-induced processing of xbp1 messenger RNA (mRNA), resulting in synthesis of new XBP1proc protein that functions as a potent transcription factor for ER stress genes. xbp1 processing in models of transient global and focal cerebral ischemia was studied.

Mechanisms underlying suppression of protein synthesis induced by transient focal cerebral ischemia in mouse brain.

Transient global cerebral ischemia triggers suppression of the initiation step of protein synthesis, a process which is controlled by endoplasmic reticulum (ER) function. ER function has been shown to be disturbed after transient cerebral ischemia, as indicated by an activation of the ER-resident eIF2alpha kinase PERK. In this study, we investigated ischemia-induced changes in protein levels and phosphorylation states of the initiation factors eIF2alpha, eIF2B epsilon, and eIF4G1 and of p70 S6 kinase, proteins playing a central role in the control of the initiation of translation.

Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease?

Ubiquitylated protein aggregates are characteristic features of neurodegenerative disorders that are also found in acute pathological states of the brain such as stroke. Many of the proteins connected to neurodegenerative diseases play a role in the ubiquitin-proteasomal pathway. Mutation of one of these proteins, the E3 ubiquitin ligase parkin, is the cause of autosomal recessive juvenile Parkinson's disease.

Genes associated with pro-apoptotic and protective mechanisms are affected differently on exposure of neuronal cell cultures to arsenite. No indication for endoplasmic reticulum stress despite activation of grp78 and gadd153 expression.

The effect of arsenite exposure on cell viability, protein synthesis, energy metabolism and the expression of genes coding for cytoplasmic (hsp70) and endoplasmic reticulum (ER; gadd153, grp78, grp94) stress proteins was investigated in primary neuronal cell cultures. Furthermore, signs of ER stress were evaluated by investigating xbp1 mRNA processing. Arsenite levels of 30 and 100 microM induced severe cell injury.

Phosphorylation state, solubility, and activity of calcium/calmodulin-dependent protein kinase II alpha in transient focal ischemia in mouse brain.

During and after middle cerebral artery occlusion in mice, CaMKII alpha protein was irreversibly translocated from the soluble to the Triton X-100-nonsoluble fraction. This decrease in solubility had a strong effect on activity: CaMKII alpha was almost completely inactivated after being translocated. Results from solubilization experiments suggest that different mechanisms underlie the conversion of CaMKII alpha protein from a soluble to a detergent nonsoluble form in ischemic as opposite to nonischemic tissue.