Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat

Infestation of the gastrointestinal tract by parasitic nematodes is invariably associated with mucosal mastocytosis, which is a thymus-dependent phenomenon in parasitized rats, and is adoptively transferable with a T cell-enriched population of thoracic duct lymphocytes. When derived by in vitro culture, mucosal mast cells (MMC) arise from a bone marrow precursor after stimulation by T cell-derived factors. In rats infected with the nematode Trichinella spiralis, mucosal mastocytosis is temporally associated with the immune expulsion of the adult worms whereas in the case of Nippostrongylus brasiliensis, mastocytosis is frequently observed to occur after worm expulsion has been completed. Consequently, there has been doubt as to whether MMC are active and serve a functional role in the expulsion of rat intestinal nematodes. MMC contain and secrete a neutral proteinase, rat mast cell protease II (RMCP II); detection and assay of secreted RMCP II therefore provides a direct measurement of MMC activity. Here we describe the release of this enzyme into the blood of rats infected with N. brasiliensis or T. spiralis. Our results show that the systemic secretion of RMCP II coincides with the immune expulsion of these nematodes, demonstrating clearly for the first time that rat MMC are functionally active during the immune elimination of primary nematode infections.     

Specificity limits of L-leucine transport in chicken small intestine

Zusammenfassung Die Darmabsorption von Leucin wurde bei Hühnern in vitro im 5-Sekunden-Versuch untersucht und ein Absorptionssystem für Leucin beschrieben.     

Specific antigen-Ia activation of transfected human T cells expressing murine Ti alpha beta-human T3 receptor complexes

The genes encoding the alpha and beta chains of the T-cell receptor (Ti) of an antigen-specific, Ia-restricted murine T-cell hybridoma were introduced into T3-positive or T3-negative human T cells. The resultant transfectants express either mouse-human or mouse-mouse Ti alpha beta molecules functionally associated with the human T3 complex. Only the complete murine Ti alpha beta dimer mediates specific functional corecognition of the appropriate antigen-Ia pair.     

The accessible surface area and stability of oligomeric proteins

Protein structures are stabilized by hydrophobic and van der Waals forces, and by hydrogen bonds. The relation between these thermodynamic quantities and the actual three-dimensional structure of proteins can not be calculated precisely. However, certain empirical relations have been discovered. Hydrophobic energy is gained by the reduction of surface in contact with water. For monomeric proteins, the area of the surface accessible to solvent, and of that buried in the interior, is a simple function of molecular weight. Proteins with different shapes and secondary structures, but of the same molecular weight, have the same accessible surface area. It has been argued that there is no similar relationship for large oligomeric proteins. In this paper we show that the surface areas of oligomeric proteins, and the areas of the surface buried within them, are directly related to relative molecular mass. Although oligomers of the same molecular weight bury the same amounts of surface, the proportions buried within and between subunits vary. This has important implications for the role of subunit interfaces in the stability and activity of oligomeric proteins.     

A submllimeter observation and study of star-forming regions

Using the 3-m radio telescope of KOSMA, we mapped 12CO (J = 3-2) lines for three molecular clouds, B35, S146 and TMC-2A. High-velocity molecular outflows are found in all these regions. The physical and dynamical parameters of the outflows are derived, and their shapes and driving sources are analyzed. Contour maps of center velocities show that the large scale systematic gradients exist in the three clouds. These observed motions are best explained by rotation after excluding the cause of outflows. Furthermore, in the core region of TMC-2A there is a velocity gradient in opposite direction from that of the large scale. It may be caused by magnetic braking. Finally, angular velocities of the clouds are calculated, and the effects of rotation against gravity and lowering the star-formation rate are also analyzed.     

Quasi-hexagonal molecular packing in collagen fibrils

Collagen molecules in native 66.8 nm (D) periodic fibrils are widely believed to be assembled into discrete, rope-like substructures, or microfibrils. Several types of microfibril have been proposed (2, 4, 5, 7- and 8-stranded) mainly on the basis of information contained in the medium angle X-ray diffraction patterns of native tendon fibres. These patterns show a series of equatorial and near-equatorial Bragg reflections which indicate that the collagen molecules are arranged on a three-dimensional crystalline lattice. The 4-stranded, 5-stranded and 8-stranded microfibrils are D-periodic with approximate diameter 3.8 nm, and these and the 2-stranded model are supposed to be packed on a three-dimensional lattice whose basal unit cell, (approximately) perpendicular to the fibril axis, is tetragonal (or quasi-tetragonal)with side a, a square root 2 or 2a, where a is approximately 3.8 nm. In this paper we describe a re-interpretation of the X-ray data which leads to a new model for the crystalline regions of the fibril, based on quasi-hexagonal molecular packing without microfibrillar sub-structures, and hence having the character of a molecular crystal.     

The role of the orbitofrontal cortex in the pursuit of happiness and more specific rewards

Cues that reliably predict rewards trigger the thoughts and emotions normally evoked by those rewards. Humans and other animals will work, often quite hard, for these cues. This is termed conditioned reinforcement. The ability to use conditioned reinforcers to guide our behaviour is normally beneficial; however, it can go awry. For example, corporate icons, such as McDonald's Golden Arches, influence consumer behaviour in powerful and sometimes surprising ways, and drug-associated cues trigger relapse to drug seeking in addicts and animals exposed to addictive drugs, even after abstinence or extinction. Yet, despite their prevalence, it is not known how conditioned reinforcers control human or other animal behaviour. One possibility is that they act through the use of the specific rewards they predict; alternatively, they could control behaviour directly by activating emotions that are independent of any specific reward. In other words, the Golden Arches may drive business because they evoke thoughts of hamburgers and fries, or instead, may be effective because they also evoke feelings of hunger or happiness. Moreover, different brain circuits could support conditioned reinforcement mediated by thoughts of specific outcomes versus more general affective information. Here we have attempted to address these questions in rats. Rats were trained to learn that different cues predicted different rewards using specialized conditioning procedures that controlled whether the cues evoked thoughts of specific outcomes or general affective representations common to different outcomes. Subsequently, these rats were given the opportunity to press levers to obtain short and otherwise unrewarded presentations of these cues. We found that rats were willing to work for cues that evoked either outcome-specific or general affective representations. Furthermore the orbitofrontal cortex, a prefrontal region important for adaptive decision-making, was critical for the former but not for the latter form of conditioned reinforcement.     

A role for the two-helix finger of the SecA ATPase in protein translocation

An important step in the biosynthesis of many proteins is their partial or complete translocation across the plasma membrane in prokaryotes or the endoplasmic reticulum membrane in eukaryotes. In bacteria, secretory proteins are generally translocated after completion of their synthesis by the interaction of the cytoplasmic ATPase SecA and a protein-conducting channel formed by the SecY complex. How SecA moves substrates through the SecY channel is unclear. However, a recent structure of a SecA-SecY complex raises the possibility that the polypeptide chain is moved by a two-helix finger domain of SecA that is inserted into the cytoplasmic opening of the SecY channel. Here we have used disulphide-bridge crosslinking to show that the loop at the tip of the two-helix finger of Escherichia coli SecA interacts with a polypeptide chain right at the entrance into the SecY pore. Mutagenesis demonstrates that a tyrosine in the loop is particularly important for translocation, but can be replaced by some other bulky, hydrophobic residues. We propose that the two-helix finger of SecA moves a polypeptide chain into the SecY channel with the tyrosine providing the major contact with the substrate, a mechanism analogous to that suggested for hexameric, protein-translocating ATPases.