Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells

Cells from the bone marrow can present peptides that are derived from tumors, transplants, and self-tissues. Here we describe how dendritic cells (DCs) process phagocytosed cell fragments onto major histocompatibility complex (MHC) class II products with unusual efficacy. This was monitored with the Y-Ae monoclonal antibody that is specific for complexes of I-Ab MHC class II presenting a peptide derived from I-Ealpha. When immature DCs from I-Ab mice were cultured for 5-20 h with activated I-E+ B blasts, either necrotic or apoptotic, the DCs produced the epitope recognized by the Y-Ae monoclonal antibody and stimulated T cells reactive with the same MHC-peptide complex. Antigen transfer was also observed with human cells, where human histocompatibility leukocyte antigen (HLA)-DRalpha includes the same peptide sequence as mouse I-Ealpha. Antigen transfer was preceded by uptake of B cell fragments into MHC class II-rich compartments. Quantitation of the amount of I-E protein in the B cell fragments revealed that phagocytosed I-E was 1-10 thousand times more efficient in generating MHC-peptide complexes than preprocessed I-E peptide. When we injected different I-E- bearing cells into C57BL/6 mice to look for a similar phenomenon in vivo, we found that short-lived migrating DCs could be processed by most of the recipient DCs in the lymph node. The consequence of antigen transfer from migratory DCs to lymph node DCs is not yet known, but we suggest that in the steady state, i.e., in the absence of stimuli for DC maturation, this transfer leads to peripheral tolerance of the T cell repertoire to self.     

A review of triticale uses and the effect of growth environment on grain quality

Triticale (× Triticosecale sp. Wittmack ex A. Camus 1927) is an anthropogenic cereal designed to incorporate the functionality and high yield of wheat (Triticum spp. Linnaeus 1753) and durability of rye (Secale cereale Linnaeus 1753). The potential of triticale has remained largely unrealised, and in the 135 years since A. Stephen Wilson first crossed wheat and rye, triticale has mostly been used as animal feed. Growing demand for food resources has led to an increased interest in triticale development. Efforts to breed cultivars appropriate for baking have met with difficulty, although relatively new approaches to triticale end-use propose greater applicability for human consumption. Further, environmental awareness has generated interest in the use of triticale within biofuel production. We review environmental and genetic effects on triticale yield with a view towards increased demand on a hardy and useful cereal crop. We find triticale could satisfy many of the hopes originally placed upon it, and may be useful in foodstuffs and fuel, but only when growth environment is carefully considered.     

Roasting affects phenolic composition and antioxidative activity of hazelnuts (Corylus avellana L.)

The potential effect of skin removal and roasting on individual and total phenolic content, and on antioxidative potential of 6 hazelnut cultivars were investigated. HPLC-MS identification of individual phenolics confirmed the presence of 7 flavan-3-ols (catechin, epicatechin, 2 procyanidin dimers, and 3 procyanidin trimers), 3 flavonols (quercetin pentoside, quercetin-3-O-rhamnoside, and myricetin-3-O-rhamnoside), 2 hydrobenzoic acids (gallic acid, protocatechulic acid), and 1 dihydrochalcone (phloretin-2'-O-glucoside). Flavonols were only detected in whole hazelnut kernels. The content of individual phenolics, with the exception of gallic acid, was always highest in whole unroasted hazelnuts and was significantly reduced after skin removal. Similarly, total phenolic content and antioxidative potential decreased when skin was removed. Roasting had a significant negative effect on individual phenolics but not on the total phenolic content and antioxidative potential of kernels. From a health promoting phytochemical composition of hazelnuts the consumption of whole unroasted kernels with skins should be preferential to peeled kernels either roasted or unroasted. Practical Application: A significant reduction in the antioxidative potential and total phenolic content is detected after hazelnut skin removal but not after roasting, suggesting that hazelnut kernels should be consumed whole. In hazelnut skin, many phenolic compounds are located, which are not present in flesh and, therefore, the health properties of hazelnuts are strongly affected by skin removal. Thermal processing and roasting conditions used in this study had a lesser effect on the individual phenolic composition of the kernel and thus roasted and unroasted hazelnuts without skin contain comparable amounts of health promoting compounds.     

Locus coeruleus lesions decrease norepinephrine input into the medial preoptic area and medial basal hypothalamus and block the LH, FSH and prolactin preovulatory surge

Phagocytosis is a fundamental process in innate resistance to infection. We have used the pathogenic yeast Cryptococcus neoformans to study the interaction of this encapsulated organism with murine macrophages in vitro. In the absence of exogenous opsonins the encapsulated yeast is almost totally resistant to ingestion by murine macrophages. Owing to its ability to activate the alternative complement pathway, the anti-phagocytic properties of the polysaccharide capsule can be partially overcome following opsonization in vitro with non-immune mouse serum and subsequent phagocytosis via complement receptors. Here, we demonstrate the importance of the complement receptor type 3 (CR3) in in vitro phagocytosis of the yeast and in in vivo resistance to infection. In vitro, 70% of a population of resident murine macrophages are able to ingest C. neoformans and then only inefficiently (1-2 organisms per cell). Previously we have shown that tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) efficiently enhance ingestion of serum-opsonized encapsulated C. neoformans, and we now show that the cytokines convert a population of resident macrophages to a state where all the cells are competent for ingestion of large numbers of yeasts (6-8 per cell). We also show that these cytokines have a direct effect on CR3, as enhanced levels of complement-opsonized sheep red blood cells (EIgMC) bind to macrophages activated in this way. However, cytokines that have previously been shown to enhance phagocytosis of EIgMC have no effect on ingestion of encapsulated C. neoformans. These results demonstrate that the cytokines regulating CR3-dependent ingestion of C. neoformans are different to those regulating ingestion of EIgMC and reinforce the importance of studying pathogens rather than inert ligands in understanding the regulation of phagocytosis.     

Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking

Essential to the dendritic cell system of antigen-presenting cells are the veiled dendritic cells that traverse afferent lymph to enter lymph nodes, where they initiate immune responses. The origin of veiled cells, which were discovered 20 years ago, is unclear. Monocytes cultured with endothelium differentiated into dendritic cells within 2 days, particularly after phagocytosing particles in subendothelial collagen. These nascent dendritic cells migrated across the endothelium in the ablumenal-to-lumenal direction, as would occur during entry into lymphatics. Monocytes that remained in the subendothelial matrix became macrophages. Therefore, monocytes have two potential fates associated with distinct patterns of migration.     

A Furnace Control System for Tracing Reference Reheating Curves

A control system for tracing the reference reheating curves of individual steel slabs in continuous furnaces is presented. The system enables the predefined, controllable reheating of slabs in a furnace. The slab temperatures are obtained by the simulation of a mathematical model of the slab‐reheating process. The interior of the continuous furnace is divided into six control zones. The individual zone temperatures are adjusted by the control system in such a way that the temperatures of the slabs in the zone are as close as possible to the desired slab temperatures. To take into account delays in the production line and to synchronize the furnace with the rolling mill's capacities, a time shift of the reference reheating curves and a prolonged drop‐out interval are introduced.     

CUTTING DISTURBANCES INFLUENCED BY VARIATIONS IN CONTACT SURFACE GEOMETRY

The significant cutting disturbances appearing in hard turning processes cause shifting of the process dynamics. Therefore, in this paper the turning process is evaluated by radial force variation analysis, as a function of depth of cut, tool nose radius and effective lead edge angle, through static and dynamic indicators. The tool/workpiece contact zone is, in the case of hard turning, mostly limited within the tool nose radius region. Therefore in this paper, geometry of the tool/workpiece contact line is analyzed. The depth of cut is calculated as a geometric difference of prior and instantaneous tool pass profiles. The calculated values of the depth of cut are time dependant, and can vary by 60%. Various process monitoring techniques have been used to identify and confirm these variations, as well as quantify the level of process stability. The results obtained confirm the assumption that effective lead edge angle and radial force are influenced by depth of cut, feed rate and tool nose radius. Additionally, it is shown that low values of depth of cut and geometry of prior pass-machined surface valleys shift the hard turning process to a dynamically more sensitive level as compared the case of soft machining.     

Novel cinnamyl hydroxyamides and 2-aminoanilides as histone deacetylase inhibitors: apoptotic induction and cytodifferentiation activity

Four novel series of cinnamyl-containing histone deacetylase (HDAC) inhibitors 1-4 are described, containing hydroxamate (1 and 3) or 2-aminoanilide (2 and 4) derivatives. When screened against class?I (maize HD1-B and human HDAC1) and class?II (maize HD1-A and human HDAC4) HDACs, most hydroxamates and 2-aminoanilides displayed potent and selective inhibition toward class?I enzymes. Immunoblotting analyses performed in U937 leukemia cells generally revealed high acetyl-H3 and low acetyl-α-tubulin levels. Exceptions are compounds 3?f-i, 3?m-o, and 4?k, which showed higher tubulin acetylation than SAHA. In U937 cells, cell-cycle blockade in either the G?/M or G?/S phase was observed with 1-4. Five hydroxamates (compounds 1?h-l) effected a two- to greater than threefold greater percent apoptosis than SAHA, and in the CD11c cytodifferentiation test some 2-aminoanilides belonging to both series 2 and 4 were more active than MS-275. The highest-scoring derivatives in terms of apoptosis (1?k, 1?l) or cytodifferentiation (2?c, 4?n) also showed antiproliferative activity in U937 cells, thus representing valuable tools for study in other cancer contexts.     

OPTODYNAMIC DEFORMATION OF A METAL PLATE ILLUMINATED BY A GAUSSIAN LASER PULSE

An analytical model is presented that describes the bending process following the absorption of a Gaussian laser pulse by the surface of a moderately thick metal plate. The model is based on the constitutive equations of thermoelastoplasticity and therefore fundamentally describes this optodynamic process. Assuming relatively short laser pulses, Green's function is used as an approximation for the real plate temperature. The plate is assumed to be made of elastic, linearly hardening material.     

Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis

Aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase, prevented the clinical development of experimental autoimmune encephalomyelitis (EAE) with a reduction in inflammation and demyelination. Administration of AG reduced the expression of nitrosotyrosine in inflammatory lesions in the central nervous system. Cytokine expression, determined by semiquantitative PCR, revealed increased expression of IFN-gamma, IL-10, and TGF-beta, which was associated with protection from EAE, and reduced TNF-alpha, associated with the development of EAE. Furthermore, AG blocked the secretion of nitric oxide, TNF-alpha, and PGE2 in astrocyte cultures. AG did not influence the proliferation response of T cells to a pathogenic epitope of myelin basic protein. Down-regulation of nitric oxide by AG has widespread consequences for cytokine production in central nervous system inflammation and prevents EAE.