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Deficiency in the E3 ubiquitin ligase Itch causes a skin-scratching phenotype in mice. We found that there was increased phosphorylation and activation of the mitogen-activated protein kinase p38α in spontaneous and experimentally induced skin lesions of Itch-deficient (Itch(-/-)) mice. Itch bound directly to the TGF-β-activated kinase 1-binding protein 1 (Tab1) through a conserved PPXY motif and
The 116m deep Fararp-1 core drilled in the Vomb Trough in southernmost Sweden is dated by integrated terrestrial and marine palynostratigraphy. The lower part of the succession (ca 84 m) encompasses uppermost Jurassic to lowermost Cretaceous (uppermost Tithonian to Valanginian) strata. An unconformity separates the Valanginian strata from an overlying ca 1 m thick interval of upper Albian to Cenom
Background: GEOMAGIA50.v3 is a comprehensive online database providing access to published paleomagnetic, rock magnetic, and chronological data from a variety of materials that record Earth's magnetic field over the past 50 ka. Findings: Since its original release in 2006, the structure and function of the database have been updated and a significant number of data have been added. Notable modific
Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee an
Importance: Excess alcohol consumption and alcohol use disorders (AUDs) are associated with substantially increased mortality. Efforts to reduce this toll require an understanding of their causes. Objective: To clarify the degree to which the excess mortality associated with AUDs arises (1) from the predispositions of the person who develops AUD (and which would likely be shared by close relatives
We study a simple heteropolymer model containing sequence-independent local interactions on both square and triangular lattices. Sticking to a two-letter code, we investigate the model for varying strength κ of the local interactions; κ=0 corresponds to the well-known HP model [K. F. Lau and K. A. Dill, Macromolecules 22, 3986 (1989)]. By exhaustive enumerations for short chains, we obtain all str
I investigate the relation between institutions, markets, and preindustrial economic growth. In particular, I analyze the impact of coercive agricultural class structures on urban population growth in Poland. My main point is that the impact of the demesne economy based on serfdom on urban growth was neither inherently negative nor positive. Instead, I suggest that the effect of serfdom depended o
The Late Ordovician mass extinction (LOME) coincided with dramatic climate changes, but there are numerous ways in which these changes could have driven marine extinctions. We use a palaeobiogeographic database of rhynchonelliform brachiopods to examine the selectivity of Late Ordovician-Early Silurian genus extinctions and evaluate which extinction drivers are best supported by the data. The firs
'Heat' diarrhea in foals is an onerous but not life-threatening ailment, which indicates that it may be of osmotic origin. This was confirmed by a successful attempt, presented in this paper, to alleviate the severity and duration of foal heat diarrhea with the use of a typical absorbent, kaolin clay, as a feed additive, usually applied in feed production as an anticaking agent. Based on the prese
The mechanisms responsible for the transfer of energy and water within the climate system are under worldwide investigation within the framework of the Global Energy and Water Cycle Experiment (GEWEX) to improve the predictability of natural and man-made climate changes at short and long ranges and their impact on water resources. Five continental-scale experiments have been established within GEW
Human cystatin C, a member of the cysteine proteinaseinhibitory family, is produced by all nucleated cells and has important roles in regulating natural immunity. Nematode homologs to human cystatin C have been shown to have anti-inflammatory effects on monocytes and to reduce colitis in mice. In Crohn’s disease, pathogenic activated monocytes help drive inflammatory processes via the release of p
Cognitively-normal people with evidence of β-amyloid (Aβ) pathology and subtle cognitive dysfunction are believed to be at high risk for progression to mild cognitive impairment due to Alzheimer's disease (AD). Clinical trials in later stages of AD typically include a coprimary endpoint to demonstrate efficacy on both cognitive and functional assessments. Recent trials focus on cognitively-normal
Aims/hypothesis: Variations in FTO are the strongest common genetic determinants of adiposity, and may partly act by influencing dopaminergic signalling in the brain leading to altered reward processing that promotes increased food intake. Therefore, we investigated the impact of such an interaction on body composition, and peripheral and brain insulin sensitivity. Methods: Participants from the T
Secretagogin is a calcium-sensor protein with six EF-hands. It is widely expressed in neurons and neuro-endocrine cells of a broad range of vertebrates including mammals, fishes and amphibia. The protein plays a role in secretion and interacts with several vesicle-associated proteins. In this work, we have studied the contribution of calcium binding and disulfide-bond formation to the stability of
