IL-9 production by regulatory T cells recruits mast cells that are essential for regulatory T cell-induced immune suppression

Both mast cells (MCs) and regulatory T cells (Tregs) have gained attention as immunosuppressive cell populations. To investigate a possible interaction, we used the Th1- and Th17-dependent model of nephrotoxic serum nephritis (NTS), in which both MCs and Tregs have been shown to play a protective role. Transfer of wild-type (wt) Tregs into wt recipients almost completely prevents development of NTS and leads to a profound increase of MCs in the renal draining lymph nodes (LNs). By contrast, transfer of wt Tregs into animals deficient in MCs, which are characterized by an exaggerated susceptibility to NTS, no longer exhibited protective effects. Blocking the pleiotropic cytokine IL-9, known to be involved in MC recruitment and proliferation, by means of a mAb in mice receiving Tregs abrogated protection from NTS. Moreover, transfer of IL-9-deficient Tregs also failed to protect from NTS. In the absence of Treg-derived IL-9, MCs fail to accumulate in the LNs, despite the fact that IL-9 deficiency does not alter the general suppressive activity of Tregs. In summary, to our knowledge, we provide the first direct in vivo evidence that the nephroprotective, anti-inflammatory effects of Tregs critically depend on IL-9-mediated attraction of MCs into kidney-draining LNs.     

Mating systems and protein–protein interactions determine evolutionary rates of primate sperm proteins

To assess the relative impact of functional constraint and post-mating sexual selection on sequence evolution of reproductive proteins, we examined 169 primate sperm proteins. In order to recognize potential genome-wide trends, we additionally analysed a sample of altogether 318 non-reproductive (brain and postsynaptic) proteins. Based on cDNAs of eight primate species (Anthropoidea), we observed that pre-mating sperm proteins engaged in sperm composition and assembly show significantly lower incidence of site-specific positive selection and overall lower non-synonymous to synonymous substitution rates (d_N/d_S) across sites as compared with post-mating sperm proteins involved in capacitation, hyperactivation, acrosome reaction and fertilization. Moreover, database screening revealed overall more intracellular protein interaction partners in pre-mating than in post-mating sperm proteins. Finally, post-mating sperm proteins evolved at significantly higher evolutionary rates than pre-mating sperm and non-reproductive proteins on the branches to multi-male breeding species, while no such increase was observed on the branches to unimale and monogamous species. We conclude that less protein–protein interactions of post-mating sperm proteins account for lowered functional constraint, allowing for stronger impact of post-mating sexual selection, while the opposite holds true for pre-mating sperm proteins. This pattern is particularly strong in multi-male breeding species showing high female promiscuity.     

Structure and Development of Viruses as Observed in the Electron Microscope: X. Entry and Uncoating of Adenovirus

Stages in the direct penetration of adenovirus through the cell membrane are illustrated. Phagocytosis with rupture of the vacuole and release of virus into the cytoplasm may also account for entry of some particles. Uncoating by digestion within phagosomes was not observed. Rather, alteration of capsid and core occurred to virions free in the cytoplasm. Nucleoprotein released from virus close to the nucleus was transported to the nuclear matrix by a unique mechanism. These events were not prevented by puromycin and hence were not dependent upon the synthesis of new enzymes. They were, however, energy-dependent.     

Carcinogenic N-hydroxylaminopurine derivatives do not act as base analog mutagens in Salmonella typhimurium

N-Hydroxylaminopurines are highly mutagenic for growing as well as resting Salmonella typhimurium strain TA100 and to a lesser extent for strain TA98. Aminopurines, under similar conditions, are not mutagenic. N-Methylhydroxylaminopurine, under similar conditions, exhibits only minimal activity. The results are taken to indicate that unlike non-hydroxylated aminopurines, N-hydroxylaminopurines exert their mutagenicity not by acting as base analogs but by direct covalent binding with DNA-guanine.     

Structural stability of soybean (Glycine max) α-amylase: properties of the unfolding transition studied with fluorescence and CD spectroscopy

Stability and unfolding of mammalian and microbial α-amylases have been intensively investigated. However, there is only limited information available on the structural stability of plant α-amylases, namely of the two isoenzymes from barley AMY1 and AMY2, of the α-amylase from mung bean (Vigna radiata), and of the α-amylase from malted sorghum (Sorghum bicolor). We report here the stability of soyabean α-amylase (GMA), against elevated temperatures and chemical denaturants (GndHCl) by employing circular dichroism and fluorescence spectroscopy. Since it is well-known that calcium ions play a crucial role for enzymatic activity and stability of a-amylases, we performed our studies with calcium bound and calcium free GMA. The thermal unfolding transition temperature decreased from 72°C for calcium saturated samples to 57°C for the case of calcium depleted GMA. Similarly, the GndHCl transition concentration was lowered from 0.70 M for calcium bound GMA to 0.41 M in the absence of calcium. Thermal unfolding of GMA irreversible due to aggregation of the unfolded state. GMA unfolded in 6 M GndHCl shows high degree of reversibility after diluting the unfolded enzyme in native buffer containing 7 M glycerol. Furthermore, the refolded enzyme showed 93% of activity.     

Morphologische Untersuchungen von Putenherzen nach Aufnahme von Fusarientoxinen durch das Futter

100 turkey poults (1 day of age) were housed in 16 boxes, each containing 6–7 animals. In each case 4 boxes constituted 4 feeding groups. One was the control group and the other three received a feed containing different quantities of the mycotoxin moniliformin (0.8; 1.6; 2.4 mg/kg) and beauvericin (0.8; 1.7; 2.5 mg/kg). The animals were fed for 12 weeks and then slaughtered. Pieces of the heart were examined by routine histology. The microscopical evaluation showed cell infiltration into the heart muscle and alterations of the heart muscle. However, a relation could be detected between the mycotoxin concentration in the feed and the frequency and the quality of heart alterations.

Presented at the 25^th Mykotoxin Workshop in Giessen, Germany, May 19–21, 2003     

Methapyrilene: DNA as a possible target

The structural features contributing to the potential carcinogenicity, DNA-reactivity and genotoxicity of methapyrilene and its non-carcinogenic congener pyrilamine were examined. The analyses suggest that the former has the potential for DNA-reactivity, a property which is absent from the latter.