Extracellular Domain N-Glycosylation Controls Human Thrombopoietin Receptor Cell Surface Levels

The thrombopoietin receptor (TpoR) is a type I transmembrane protein that mediates the signaling functions of thrombopoietin (Tpo) in regulating megakaryocyte differentiation, platelet formation, and hematopoietic stem cell renewal. We probed the role of each of the four extracellular domain putative N-glycosylation sites for cell surface localization and function of the receptor. Single N-glycosylation mutants at any of the four sites were able to acquire the mature N-glycosylated pattern, but exhibited a decreased Tpo-dependent JAK2–STAT response in stably transduced Ba/F3 or Ba/F3-JAK2 cell lines. The ability of JAK2 to promote cell surface localization and stability of TpoR required the first N-glycosylation site (Asn117). In contrast, the third N-glycosylation site (Asn298) decreased receptor maturation and stability. TpoR mutants lacking three N-glycosylation sites were defective in maturation, but N-glycosylation on the single remaining site could be detected by sensitivity to PNGaseF. The TpoR mutant defective in all four N-glycosylation sites was severely impaired in plasma membrane localization and was degraded by the proteasome. N-glycosylation receptor mutants are not misfolded as, once localized on the cell surface in overexpression conditions, they can bind and respond to Tpo. Our data indicate that extracellular domain N-glycosylation sites regulate in a combinatorial manner cell surface localization of TpoR. We discuss how mutations around TpoR N-glycosylation sites might contribute to inefficient receptor traffic and disease

A cartographical perspective to the engineering works at the Sulina mouth

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Akadémiai Kiadó for personal use, not for redistribution. The definitive version was published in Acta Geodaetica et Geophysica Hungarica 45 (2010): 71-79, doi:10.1556/AGeod.45.2010.1.11.From 1856 to 1939, the European Commission of the Danube (ECD), was responsible for technical surveys at the mouth of Sulina arm. During this period, ECD prepared general maps of Danube Delta as well as detailed charts for all the Danube mouths: Chilia, Sulina and Sf. Gheorghe (St. George) that were published in various reports or atlases. ECD used a local grid network benchmarked at Sulina, divided in 500 feet units. The reference point was the old lighthouse located on the right bank of Danube. After the Second World War, the Romanian authorities elaborated new cartographical products using the Gauss‐Kruger projection or Stereo‐70 like national grid. Our goal is to generate a cartographical background database necessary for refining the coastal evolution model of the Sulina mouth. To handle the large number of available maps, we chose GeoNetwork like a solution for catalog service, indexing and defining metadata. The service is operating at geo‐spatial.org

Neurobiology of Vascular Dementia

Vascular dementia is, in its current conceptual form, a distinct type of dementia with a spectrum of specific clinical and pathophysiological features. However, in a very large majority of cases, these alterations occur in an already aged brain, characterized by a milieu of cellular and molecular events common for different neurodegenerative diseases. The cell signaling defects and molecular dyshomeostasis might lead to neuronal malfunction prior to the death of neurons and the alteration of neuronal networks. In the present paper, we explore some of the molecular mechanisms underlying brain malfunction triggered by cerebrovascular disease and risk factors. We suggest that, in the age of genetic investigation and molecular diagnosis, the concept of vascular dementia needs a new approach

Cohesive and XFEM evaluation of adhesive failure for dissimilar single-lap joints

AbstractCohesive Zone Modelling (CZM) and eXtended Finite Element Modelling (XFEM) available in Abaqus® are used together to simulate the behaviour and strength of dissimilar single-lap adhesively bonded joints. A distinct CZM model is also used. Single-lap joints made of aluminium and carbon fibre adherends of different thickness are tested to understand better the behaviour of such dissimilar joints. Local deformation fields are monitored by using the digital image correlation method (DIC). Peeling and shearing strains are investigated, emphasizing that peeling is important in the region where failure is initiated, towards an extremity of the overlap region. The use of dissimilar adherends is reducing the strength and stiffness of the joints as the delamination and pull-out of the carbon fibres reduces the integrity of the joint. The experimental evidence given by DIC is not to be obtained by numerical simulations

Influence of cell wall curvature radius and adhesive layer on the effective elastic out-of-plane properties of hexagonal honeycombs

Numerical modeling of honeycomb structures in aerospace engineering is too tedious and time consuming. The homogenization of these structures permits to obtain an equivalent orthotropic homogeneous solid and its elastic effective properties and thus realizing very efficient simulations. In a sandwich structure the most important effective constants of the core are the out-of-plane shear moduli G23 and G13. These particular effective constants can be obtained analytically, numerically or, if available, can be taken from the producer's data sheets. In the last case they are generally obtained experimentally, but only for some particular thicknesses of the cores and sandwich faces. The analytical models usually neglect the curvature radius of the cell walls and the adhesive layer influence by using some additional hypotheses. In this paper a general parameterization of commercial honeycombs is first discussed. Then, neglecting the skin effect and considering the rigid skin effect, the out-of-plane properties of the core are obtained using a finite element analysis of a representative volume element. The numerical results are analyzed by comparing them to the ones given by the existing analytical models and/or experimental data and their advantages and pitfalls are discussed and explained. The results provide new insights into understanding the mechanics of honeycombs