Analysis of heat-induced localization of ESCRTIII core and associated proteins to mRNP granules in A. thaliana

Endosomes are key sorting compartments in the endomembrane system, including the sorting of transmembrane proteins for degradation. This is achieved by a endocytic event in which the cargo-enriched endosomal membrane buds away from the cytosol and releases an intraluminal vesicle (ILV) into the endosomal lumen. Endosomes that contain ILVs are called multivesicular bodies (MVBs) and ILVs together with their cargo are finally degraded by the fusion of MVBs with the vacuole. ILV formation is executed by evolutionary conserved multi-protein complexes that are called the Endosomal Sorting Complex Required for Transport (ESCRT) system. The late steps of ILV formation are regulated by the ESCRTIII core and associated complex, in which the AAA-ATPase SUPPRESSOR OF K(+) TRANSPORT GROWTH DEFECT 1 (SKD1) is the key enzyme. Recent studies in Arabidopsis thaliana showed that SPIRRIG, a stimulator of SKD1 function in MVB formation, has also a function in the stress-dependent formation of Processing bodies (P-bodies). P-bodies, together with stress granules, are two classes of mRNA-ribonucleoprotein (mRNP) granules that sequester mRNAs during stress-induced polysome disassembly. To see, if other late acting ESCRTIII proteins are associated with mRNP granules, an exhaustive colocalization study was performed. This study showed that SKD1 changes its subcellular localization after heat stress to mRNP granules, independent of MVBs. Other ESCRTIII associated proteins, but none of the tested ESCRTIII core proteins, colocalized to mRNP granule markers. The sequestration of SKD1 and some of its cofactors in mRNP granules led to the hypothesis, that ESCRT trafficking might be temporarily blocked during heat stress. First evidence supporting this hypothesis was gained by the study of the subcellular localization of PIN-FORMED 2, which is transported by ESCRT, after heat stress. In a broader approach, the interactome of SKD1 was analyzed. Several proteins known to associate with mRNP granules were identified, such as members of the chaperonin-containing T-complex or the P-body protein VARICOSE. In addition, new potential interactions with other membrane trafficking proteins, such as members of the homotypic fusion and vacuole protein sorting (HOPS)/class C core vacuole/endosome tethering (CORVET) complex, were identified. A subcellular localization analysis confirmed the association of some candidates with mRNP granules after heat stress and indicated that proteins of other membrane trafficking routes might also be recruited to mRNP granules by heat stress

Development of multifunction ladder

The objective of this thesis is to develop and fabricate the multifunction ladder and to minimize the manufacturing cost. Ladder is equipment that can easier consumer’s daily activities at higher place. It is stable and safe to use. The concept of this project is based on student’s creativity. The characteristics of material to fabricate this ladder are lightweight, longer life span, corrosion resistance and can take maximum load. Thus, the suitable material that accomplished those characteristics is aluminium alloy. In this thesis, we’ll also be having more to the fabrication of this ladder

Reduced pain perception in children and adolescents with ADHD is normalized by methylphenidate

Background: The present study examined pain perception in children and adolescents with ADHD and the interaction between pain perception and the administration of methylphenidate (MPH) in order to generate hypotheses for further research that will help to clarify the association between ADHD diagnosis, MPH treatment and pain perception. Methods: We included 260 children and adolescents of the “German Health Interview and Examination Survey for Children and Adolescents” (KiGGS) and analyzed parent’s assessments of children’s pain distribution and pain perception, as well as the influence of MPH administration on pain perception in affected children and adolescents. Results: Pain perception was associated with ADHD and MPH administration, indicating that children and adolescents suffering from ADHD without MPH treatment were reported to have lower pain perception compared to both, healthy controls (HC) and ADHD patients medicated with MPH. Conclusion: We suggest that reduced pain perception in children and adolescents with ADHD not medicated with MPH may lead to higher risk tolerance by misjudgments of dangerous situations, expanding the importance of MPH administration in affected children and adolescents

Twitter als interaktive Erweiterung des Mediums Fernsehen: Inhaltliche Analyse von Tatort-Tweets

Dieser Beitrag beschreibt eine Studie zur Nutzung von Twitter als interaktive Erweiterung des statischen Mediums Fernsehen. Dabei wurden ca. 3.700 Live-Tweets zu einer Folge der deutschen Krimireihe Tatort nach Inhalt und Funktion kategorisiert und anschließend in Hinblick auf vornehmlich medienwissenschaftliche Erkenntnisinteressen untersucht. Die Studie liefert Ergebnisse zur Medienkonvergenz von Twitter und der Krimireihe Tatort

Multimorbidity Patterns in the Elderly: A New Approach of Disease Clustering Identifies Complex Interrelations between Chronic Conditions

Objective: Multimorbidity is a common problem in the elderly that is significantly associated with higher mortality, increased disability and functional decline. Information about interactions of chronic diseases can help to facilitate diagnosis, amend prevention and enhance the patients ’ quality of life. The aim of this study was to increase the knowledge of specific processes of multimorbidity in an unselected elderly population by identifying patterns of statistically significantly associated comorbidity. Methods: Multimorbidity patterns were identified by exploratory tetrachoric factor analysis based on claims data of 63,104 males and 86,176 females in the age group 65+. Analyses were based on 46 diagnosis groups incorporating all ICD-10 diagnoses of chronic diseases with a prevalence $ 1%. Both genders were analyzed separately. Persons were assigned to multimorbidity patterns if they had at least three diagnosis groups with a factor loading of 0.25 on the corresponding pattern. Results: Three multimorbidity patterns were found: 1) cardiovascular/metabolic disorders [prevalence female: 30%; male: 39%], 2) anxiety/depression/somatoform disorders and pain [34%; 22%], and 3) neuropsychiatric disorders [6%; 0.8%]. The sampling adequacy was meritorious (Kaiser-Meyer-Olkin measure: 0.85 and 0.84, respectively) and the factors explained a large part of the variance (cumulative percent: 78 % and 75%, respectively). The patterns were largely age-dependent an

Which chronic diseases and disease combinations are specific to multimorbidity in the elderly? Results of a claims data based cross-sectional study in Germany

<p>Abstract</p> <p>Background</p> <p>Growing interest in multimorbidity is observable in industrialized countries. For Germany, the increasing attention still goes still hand in hand with a small number of studies on multimorbidity. The authors report the first results of a cross-sectional study on a large sample of policy holders (n = 123,224) of a statutory health insurance company operating nationwide. This is the first comprehensive study addressing multimorbidity on the basis of German claims data. The main research question was to find out which chronic diseases and disease combinations are specific to multimorbidity in the elderly.</p> <p>Methods</p> <p>The study is based on the claims data of all insured policy holders aged 65 and older (n = 123,224). Adjustment for age and gender was performed for the German population in 2004. A person was defined as multimorbid if she/he had at least 3 diagnoses out of a list of 46 chronic conditions in three or more quarters within the one-year observation period. Prevalences and risk-ratios were calculated for the multimorbid and non-multimorbid samples in order to identify diagnoses more specific to multimorbidity and to detect excess prevalences of multimorbidity patterns.</p> <p>Results</p> <p>62% of the sample was multimorbid. Women in general and patients receiving statutory nursing care due to disability are overrepresented in the multimorbid sample. Out of the possible 15,180 combinations of three chronic conditions, 15,024 (99%) were found in the database. Regardless of this wide variety of combinations, the most prevalent individual chronic conditions do also dominate the combinations: Triads of the six most prevalent individual chronic conditions (hypertension, lipid metabolism disorders, chronic low back pain, diabetes mellitus, osteoarthritis and chronic ischemic heart disease) span the disease spectrum of 42% of the multimorbid sample. Gender differences were minor. Observed-to-expected ratios were highest when purine/pyrimidine metabolism disorders/gout and osteoarthritis were part of the multimorbidity patterns.</p> <p>Conclusions</p> <p>The above list of dominating chronic conditions and their combinations could present a pragmatic start for the development of needed guidelines related to multimorbidity.</p

Arf6 regulates AP-1B–dependent sorting in polarized epithelial cells

Activated Arf6 directs membrane recruitment of the clathrin adaptor AP-1B to maintain membrane polarization in epithelial cells

Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants:findings from the Prospective Lynch Syndrome Database

Purpose Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. Methods We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. Results There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. Conclusion Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers

Human transformations of the Wadden Sea ecosystem through time: a synthesis

Todayrsquos Wadden Sea is a heavily human-altered ecosystem. Shaped by natural forces since its origin 7,500 years ago, humans gradually gained dominance in influencing ecosystem structure and functioning. Here, we reconstruct the timeline of human impacts and the history of ecological changes in the Wadden Sea. We then discuss the ecosystem and societal consequences of observed changes, and conclude with management implications. Human influences have intensified and multiplied over time. Large-scale habitat transformation over the last 1,000 years has eliminated diverse terrestrial, freshwater, brackish and marine habitats. Intensive exploitation of everything from oysters to whales has depleted most large predators and habitat-building species since medieval times. In the twentieth century, pollution, eutrophication, species invasions and, presumably, climate change have had marked impacts on the Wadden Sea flora and fauna. Yet habitat loss and overexploitation were the two main causes for the extinction or severe depletion of 144 species (~20% of total macrobiota). The loss of biodiversity, large predators, special habitats, filter and storage capacity, and degradation in water quality have led to a simplification and homogenisation of the food web structure and ecosystem functioning that has affected the Wadden Sea ecosystem and coastal societies alike. Recent conservation efforts have reversed some negative trends by enabling some birds and mammals to recover and by creating new economic options for society. The Wadden Sea history provides a unique long-term perspective on ecological change, new objectives for conservation, restoration and management, and an ecological baseline that allows us to envision a rich, productive and diverse Wadden Sea ecosystem and coastal society