Hereditary hemochromatosis: Effects of C282Y and H63D mutations on association with β2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells

Hereditary hemochromatosis (HH) is the most common autosomal recessive disorder known in humans. A candidate gene for HH called HFE has recently been cloned that encodes a novel member of the major histocompatibility complex class I family. Most HH patients are homozygous for a Cys-282→Tyr (C282Y) mutation in HFE gene, which has been shown to disrupt interaction with β2-microglobulin; a second mutation, His-63→Asp (H63D), is enriched in HH patients who are heterozygous for C282Y mutation. The aims of this study were to determine the effects of the C282Y and H63D mutations on the cellular trafficking and degradation of the HFE protein in transfected COS-7 cells. The results indicate that, while the wild-type and H63D HFE proteins associate with β2-microglobulin and are expressed on the cell surface of COS-7 cells, these capabilities are lost by the C282Y HFE protein. We present biochemical and immunofluorescence data that indicate that the C282Y mutant protein: (i) is retained in the endoplasmic reticulum and middle Golgi compartment, (ii) fails to undergo late Golgi processing, and (iii) is subject to accelerated degradation. The block in intracellular transport, accelerated turnover, and failure of the C282Y protein to be presented normally on the cell surface provide a possible basis for impaired function of this mutant protein in HH.

The Thrombospondin Receptor CD47 (IAP) Modulates and Associates with α2β1 Integrin in Vascular Smooth Muscle Cells

The carboxyl-terminal domain of thrombospondin-1 enhances the migration and proliferation of smooth muscle cells. Integrin-associated protein (IAP or CD47) is a receptor for the thrombospondin-1 carboxyl-terminal cell-binding domain and binds the agonist peptide 4N1K (kRFYVVMWKk) from this domain. 4N1K peptide stimulates chemotaxis of both human and rat aortic smooth muscle cells on gelatin-coated filters. The migration on gelatin is specifically blocked by monoclonal antibodies against IAP and a β1 integrin, rather than αvβ3 as found previously for 4N1K-stimulated chemotaxis of endothelial cells on gelatin. Both human and rat smooth muscle cells displayed a weak migratory response to soluble type I collagen; however, the presence of 4N1K peptide or intact thrombospondin-1 provoked a synergistic chemotactic response that was partially blocked by antibodies to α2 and β1 integrin subunits and to IAP. A combination of antiα2 and IAP monoclonal antibodies completely blocked chemotaxis. RGD peptide and antiαvβ3 mAb were without effect. 4N1K and thrombospondin-1 did not augment the chemotactic response of smooth muscle cells to fibronectin, vitronectin, or collagenase-digested type I collagen. Complex formation between α2β1 and IAP was detected by the coimmunoprecipitation of both α2 and β1 integrin subunits with IAP. These data suggest that IAP can associate with α2β1 integrin and modulate its function.

An improvement of a SLAM RGB-D method with movement prediction derived from a study of visual features

This paper presents a method for the fast calculation of a robot’s egomotion using visual features. The method is part of a complete system for automatic map building and Simultaneous Location and Mapping (SLAM). The method uses optical flow to determine whether the robot has undergone a movement. If so, some visual features that do not satisfy several criteria are deleted, and then egomotion is calculated. Thus, the proposed method improves the efficiency of the whole process because not all the data is processed. We use a state-of-the-art algorithm (TORO) to rectify the map and solve the SLAM problem. Additionally, a study of different visual detectors and descriptors has been conducted to identify which of them are more suitable for the SLAM problem. Finally, a navigation method is described using the map obtained from the SLAM solution.

Terry's guide to Cuba, including the Isle of Pinea, with a chapter on the ocean routes to the island; a handbook for travelers, with 2 specially drawn maps and 7 plans,

Mode of access: Internet.

A synopsis of British plants, in Mr. Ray's method, with their characters, descriptions, places of growth, time of flowering, and physical virtues. Together with a botanical dictionary.

Mode of access: Internet.

Candid reasons for renouncing the principles of antipaedobaptism. Also, an appendix, containing A short method with the Baptists.

Mode of access: Internet.

A descriptive catalogue of recent shells, arranged according to the Linnæan method; with particular attention to the synonymy.

Paged continuously.

Direct and general support maintenance repair parts and special tools list (including depot maintenance repair parts and special tools) : loader, scoop type, pneu-tired, diesel engine driven, hinged frame steer with 2 1/2 cubic yard multi-purpose bucket, (Allis-Chalmers model 645M), FSN 3805-051-9359.

Includes index.

Operator and organizational maintenance manual : loader, scoop type, pneu-tired, diesel engine driven, hinged frame steer with 2 1/2 cu yd multi-purpose bucket, Allis-Chalmers model 645M, FSN 3805-051-9359.

"July 1968."

Organizational maintenance repair parts and special tools list : loader, scoop type, pneu-tired, diesel engine driven, hinged frame steer, with 2 1/2 cubic yard multi-purpose bucket (Allis-Chalmers model 645M) FSN 3805-051-9359.

"August 1974."

Direct and general support and depot maintenance manual : loader scoop type, pneu tired, diesel engine driven, hinged frame steer, with 2-1/2 cu yd multi-purpose bucket, Allis Chalmers model 645M, FSN 3805-051-9359.

Includes index.

Operator and organizational maintenance manual : loader, scoop type, pneu-tired, diesel engine driven, hinged frame steer with 2 1/2 cu yd multi-purpose bucket, Allis-Chalmers model 645M, FSN 3805-051-9359.

"July 1968."

Responses and residues in sugarbeets, soybeans, and corn irrigated with 2,4,-D or silvex-treated water /

"Agricultural Research Service...in cooperation with College of Agriculture, Washington State University and under contract with Pacific Northwest Laboratories, Battelle Memorial Institute."

A short method with modern doubt. A centenary contribution. In three parts: 1. Jesus His own proof. II. The laws of nature. III. Correspondence with Spinoza.

Mode of access: Internet.