Arrangement of subunits in 20 S particles consisting of NSF, SNAPs, and SNARE complexes

The present study attempts to identify the antigen-presenting cells in the retina, utilizing bone marrow-transplanted chimeric rats. Two types of chimeras were used: one produced by transplanting bone marrow cells from F1 hybrids of Lewis and Brown Norway (BN) into sublethally irradiated Brown Norway rats (LBN/F1-->BN), followed by adoptive transfer of S-antigen-specific T cells obtained from Lewis rats; the second produced by transplanting bone marrow cells from BN rats into sublethally irradiated F1 hybrids (BN-->LBN/F1), followed by adoptive transfer of S-antigen-specific T cells obtained from F1 hybrids. As controls, Lewis, F1 hybrids and BN rats also received adoptive transfer of syngeneic uveitogenic T cell lines. All animals were killed on the seventh day after adoptive transfer and their eyes and pineal glands were analysed immunohistochemically, utilizing antibody directed against Lewis specific MHC class II molecules(OX-3). The analyses revealed the development of uveoretinitis and pinealitis in both types of chimeras and in the Lewis and F1 hybrid rats. BN rats did not develop uveoretinitis. OX-3-positive cells were found in the retina and the pineal glands of both types of chimeras, and in the Lewis and F1 hybrid rats but not in the BN rats. These cells in the retina expressed dendritic morphology and perivascular distribution. Retinal pigment epithelia, Müller cells and the vascular endothelia of both chimeras, the two strains, and the F1 hybrid rats did not demonstrate OX-3-positive staining. These results suggest that the bone marrow-derived cells in the retina and pineal gland may present S-antigen to T cells, initiating the cascade of uveoretinitis and pinealitis.     

Isoprenoids: Remarkable diversity of form and function

The isoprenoid biosynthetic pathway is the source of a wide array of products. The pathway has been highly conserved throughout evolution, and isoprenoids are some of the most ancient biomolecules ever identified, playing key roles in many life forms. In this review we focus on C-10 mono-, C-15 sesqui-, and C-20 diterpenes. Evidence for interconversion between the pathway intermediates farnesyl pyrophosphate and geranylgeranly pyrophosphate and their respective metabolites is examined. The diverse functions of these molecules are discussed in detail, including their ability to regulate expression of the β-HMG-CoA reductase and Ras-related proteins. Additional topics include the mechanisms underlying the apoptotic effects of select isoprenoids, antiulcer activities, and the disposition and degradation of isoprenoids in the environment. Finally, the significance of pharmacological manipulation of the isoprenoid pathway and clinical correlations are discussed.     

Integration of varying spatial,spectral and temporal high-resolution optical images for individual tree crown isolation

Automated methods for capturing geometric and spectral properties of individual tree crowns are becoming increasingly viable options for use in natural resource planning. Crown isolation techniques are needed that are capable of adapting to the changing availability and resolutions of remotely sensed data. Data integration, or the fusion of two distinct data entities, offers a methodological framework that can compensate for the shortcomings of individual datasets while enhancing their desirable features. This study sought to develop a method of data integration for high-resolution optical images of varying spatial and temporal resolutions to improve the automatic detection and delineation of individual tree crowns. A marker-controlled watershed segmentation (MCWS) algorithm was developed for a 30-cm-per-pixel-side airborne colour infrared (CIR) digital image of a leaf-on apple (Malus spp.) orchard. Three methods of obtaining the markers needed for the MCWS algorithm were tested: (1) manual marker selection, (2) template/correlation selection using the 30-cm CIR image, and (3) template/correlation selection using a 15-cm-per-pixel-side true (TRU) colour leaf-off aerial image. The effectiveness of integrating marker data of different temporal and spatial resolutions with the segmentation process of the CIR image scene was tested. A comparison of crown isolation results using markers derived within the segmented 30-cm CIR digital imagery with results from markers derived from the 15-cm TRU image scene indicated greater accuracies to detect and isolate tree crowns with data integration.     

Steatocystoma multiplex and oligosymptomatic pachyonychia congenita of the Jackson-Sertoli type

Two cases of ventriculo-peritoneal (V-P) shunt infection attributable to intestinal perforation are reported. One patient developed a brain abscess, the other ventriculitis. Microbiology consisted of faecal flora and the peritoneal catheter was found to be faecally stained in both cases. There were no abdominal symptoms or signs. It is likely that infection developed via the ascending route.     

3-Deoxyschweinfurthin B Lowers Cholesterol Levels by Decreasing Synthesis and Increasing Export in Cultured Cancer Cell Lines

The schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3‐deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X‐receptor (LXR) activation. The effects of 3dSB on ATP‐binding cassette transporter 1 levels and other LXR targets are similar to that of 25‐hydroxycholesterol, an LXR agonist. Unlike 25‐hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.     

Fibroblast Growth Factor 21 Response in a Preclinical Alcohol Model of Acute-on-Chronic Liver Injury

Background and Aims: Fibroblast growth factor (FGF) 21 has recently been shown to play a potential role in bile acid metabolism. We aimed to investigate the FGF21 response in an ethanol-induced acute-on-chronic liver injury (ACLI) model in Abcb4^−/− mice with deficiency of the hepatobiliary phospholipid transporter. Methods: Total RNA was extracted from wild-type (WT, C57BL/6J) and Abcb4⁻/⁻ (KO) mice, which were either fed a control diet (WT-Cont and KO-Cont groups; n = 28/group) or ethanol diet, followed by an acute ethanol binge (WT-EtOH and KO-EtOH groups; n = 28/group). A total of 58 human subjects were recruited into the study, including patients with alcohol-associated liver disease (AALD; n = 31) and healthy controls (n = 27). The hepatic and ileal expressions of genes involved in bile acid metabolism, plasma FGF levels, and bile acid and its precursors 7α- and 27-hydroxycholesterol (7α- and 27-OHC) concentrations were determined. Primary mouse hepatocytes were isolated for cell culture experiments. Results: Alcohol feeding significantly induced plasma FGF21 and decreased hepatic Cyp7a1 levels. Hepatic expression levels of Fibroblast growth factor receptor 1 (Fgfr1), Fgfr4, Farnesoid X-activated receptor (Fxr), and Small heterodimer partner (Shp) and plasma FGF15/FGF19 levels did not differ with alcohol challenge. Exogenous FGF21 treatment suppressed Cyp7a1 in a dose-dependent manner in vitro. AALD patients showed markedly higher FGF21 and lower 7α-OHC plasma levels while FGF19 did not differ. Conclusions: The simultaneous upregulation of FGF21 and downregulation of Cyp7a1 expressions upon chronic plus binge alcohol feeding together with the invariant plasma FGF15 and hepatic Shp and Fxr levels suggest the presence of a direct regulatory mechanism of FGF21 on bile acid homeostasis through inhibition of CYP7A1 by an FGF15-independent pathway in this ACLI model. Lay Summary: Alcohol challenge results in the upregulation of FGF21 and repression of Cyp7a1 expressions while circulating FGF15 and hepatic Shp and Fxr levels remain constant both in healthy and pre-injured livers, suggesting the presence of an alternative FGF15-independent regulatory mechanism of FGF21 on bile acid homeostasis through the inhibition of Cyp7a1.     

Porous hip replacement in Paget's disease. An 8-2/3-year followup

An 8-year 8-month followup of a now 78-year-old active woman with a painful, severe varus deformity of the femur and arthritis of the right hip associated with monostotic Paget's disease of the hip is presented. Treatment consisted of multiple osteotomies, followed by implantation of a long stemmed cobalt chrome fully coated porous ingrowth hip system. The patient had an excellent outcome, including relief of pain and restoration of excellent function, despite ongoing severe osteolytic changes that did not appear to influence the healing of the osteotomies or the clinical stability of the implant.     

Fractures of the humerus in children

Fractures of the humerus above the distal epiphysis are not common fractures in children. Treatment should be directed toward maintenance of alignment with healing expected without fail. Contrary to experience with adults with the same fractures, children seldom have residual functional or cosmetic problems if one aligns the fractures and protects the healing process.     

Mole – Concepts of a mobile agent system

Due to its salient properties, mobile agent technology has received a rapidly growing attention over the last few years. Many developments of mobile agent systems are under way in both academic and industrial environments. In addition, there are already various efforts to standardize mobile agent facilities and architectures. Mole is the first mobile agent system that has been developed in the Java language. The first version was finished in 1995, and since then Mole has been constantly improved. Mole provides a stable environment for the development and usage of mobile agents in the area of distributed applications. In this paper we describe the basic concepts of a mobile agent system, i.e., mobility, communication and security, discuss different implementation techniques, present the decisions made in Mole and give an overview of the system services implemented in Mole.