FUS/TLS is a nucleic acid binding protein that, when mutated, can cause a subset of familial amyotrophic lateral sclerosis (fALS). Although FUS/TLS is normally located predominantly in the nucleus, ...the pathogenic mutant forms of FUS/TLS traffic to, and form inclusions in, the cytoplasm of affected spinal motor neurons or glia. Here we report a yeast model of human FUS/TLS expression that recapitulates multiple salient features of the pathology of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, inclusion formation, and cytotoxicity. Protein domain analysis indicates that the carboxyl-terminus of FUS/TLS, where most of the ALS-associated mutations are clustered, is required but not sufficient for the toxicity of the protein. A genome-wide genetic screen using a yeast over-expression library identified five yeast DNA/RNA binding proteins, encoded by the yeast genes ECM32, NAM8, SBP1, SKO1, and VHR1, that rescue the toxicity of human FUS/TLS without changing its expression level, cytoplasmic translocation, or inclusion formation. Furthermore, hUPF1, a human homologue of ECM32, also rescues the toxicity of FUS/TLS in this model, validating the yeast model and implicating a possible insufficiency in RNA processing or the RNA quality control machinery in the mechanism of FUS/TLS mediated toxicity. Examination of the effect of FUS/TLS expression on the decay of selected mRNAs in yeast indicates that the nonsense-mediated decay pathway is probably not the major determinant of either toxicity or suppression.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: As visceral protein expression may influence outcomes in patients with cardiovascular disease, we investigated whether pre-procedural albumin concentration is associated with length of ...stay (LOS) and 90-day mortality after transcatheter aortic valve repair (TAVR).
Methods: We retrospectively analyzed data from TAVR patients at our institution between January 2013 and December 2017. For all patients, baseline albumin concentration was assessed between one and four weeks before the procedure. To investigate the association between albumin concentration and outcomes, we performed regression analyses, controlling for Society of Thoracic Surgeons, New York Heart Association classification, and Kansas City Cardiomyopathy Questionnaire 12 scores.
Results: Three hundred eighty patients were included in the analyses. Cox-proportional hazards regression showed that patients with albumin concentrations <3.5 g/dL were 80% more likely to have prolonged ICU LOS (HR 1.79; 95%CI 1.04-2.57, P = 0.03) and 70% more likely to have prolonged hospital LOS (HR 1.68; 95%CI 1.01-2.46, P = 0.04) compared to patients with albumin concentrations >3.5 g/dL. Logistic regression showed that patients with albumin concentrations <3.5 g/dL were four times more likely to not survive to 90 days (OR 3.94; 1.13-12.63, P = 0.03) after their TAVR compared to patients with albumin concentrations >3.5 g/dL.
Conclusion: Our data suggest that patients with pre-procedural albumin concentrations <3.5 g/dL are at an increased risk of adverse outcomes after TAVR compared to patients with albumin concentrations ≥3.5 g/dL. Prospective studies are needed to determine whether risk stratification based on pre-procedural albumin can improve outcomes and whether targeted interventions can improve pre-procedural albumin concentrations in potential TAVR candidates.
Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity ...modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.
•There is no preferred mode of anesthesia for cesarean section delivery of paturients with severe PAH.•Cesarean sections in parturients with PAH have been successfully managed both with general ...anesthesia and neuraxial anesthesia.•A cardiothoracic surgery team should be on standby in the event of the need for back-up extra-corporal membrane oxygenation.•Cesarean sections in pregnant women with PAH require complex pre-, intra- and post-operative management
Yeast cell biology has yielded fundamental insight into a variety of processes involved in human disease. Treusch et al. (p. 1241, published online 27 October; see the Perspective by McGurk and ...Bonini) have now created a yeast model of the cellular toxicity caused by the beta-Amyloid peptide Aβ 1-42, which is thought to be causal in Alzheimer's disease (AD). An unbiased genome-wide screen for modifiers of toxicity revealed the yeast homolog of PICALM, a confirmed AD risk factor involved in endocytosis. Three additional genes were also identified that appear to impact AD risk, based on their associations with AD onset and pathologic burden. A model of Aβ toxicity in the glutamatergic neurons of nematodes was created and used to confirm the role of the toxicity modifiers. PICALM was also shown to protect rat cortical neurons from toxic Aβ oligomers. Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system. PUBLICATION ABSTRACT
The purpose of this study was to examine the influence of egoistic and altruistic values on purchase behaviors of organic cotton apparel. Our findings indicated that egoistic, social-altruistic, and ...biospheric values have a positive and significant effect on purchase intentions. In addition, when examining the effectiveness of egoistic and altruistic claims in organic cotton apparel advertising, we found a significant effect of advertising claim type on brand attitudes, product attitudes, and purchase intentions. Organic cotton apparel ads were the most effective in persuading consumers when they contain egoistic claims such as information about low price and personal health benefits. The findings suggested that altruistic claims alone may not be effective in promoting purchase behaviors and thus should be combined with egoistic claims. While it is widely accepted that altruistic considerations foster green apparel purchase behaviors, egoistic aspects of the purchase are often ignored. However, our findings showed that egoistic motives may play an important role in the purchase process of organic cotton apparel. Therefore, it would be important for marketers of organic cotton apparel to link such products to consumers' egoistic considerations.
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