Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.     

Preliminary observations concerning the effect of dopamine on uranyl nitrate induced renal failure

Summary Dopamine infusion, when commenced 24 h after the insult, was ineffective in modifying the course of uranyl nitrate induced renal failure in rabbits.Acknowledgments. This study was supported in part by the Lillian and Charles Duncan Research Grant for the Investigation of Factors Affecting Atherogenesis. The dopamine was provided by Arnar-Stone Laboratories, Inc.     

cGMP-dependent protein kinase enhances Ca2+ current and potentiates the serotonin-induced Ca2+ current increase in snail neurones

Protein phosphorylation catalysed by cyclic AMP-dependent, Ca2+/calmodulin-dependent and Ca2+/diacylglycerol-dependent protein kinases is important both in the modulation of synaptic transmission and in the regulation of neuronal membrane permeability (for reviews see refs 5-7). However, there has previously been no evidence for the involvement of cyclic GMP-dependent protein kinase (cGMP-PK) in the regulation of neuronal function. Serotonin induces an increase of Ca2+ current in a group of identified ventral neurones of the snail Helix aspersa. This effect is probably mediated by cGMP because it is mimicked by the intracellular injection of cGMP or the application of zaprinast, an inhibitor of cGMP-dependent phosphodiesterase. We have now found that the effect of either serotonin or zaprinast on the Ca2+ current is potentiated by the intracellular injection of cGMP-PK. Moreover, the intracellular injection of activated cGMP-PK (cGMP-PK + 1 microM cGMP) greatly enhances the Ca2+ current of the identified ventral neurones seen in the absence of serotonin. These results indicate that cGMP-PK has a physiological role in the control of the membrane permeability of these neurones.     

A micrococcal nuclease homologue in RNAi effector complexes

RNA interference (RNAi) regulates gene expression by the cleavage of messenger RNA, by mRNA degradation and by preventing protein synthesis. These effects are mediated by a ribonucleoprotein complex known as RISC (RNA-induced silencing complex). We have previously identified four Drosophila components (short interfering RNAs, Argonaute 2 (ref. 2), VIG and FXR) of a RISC enzyme that degrades specific mRNAs in response to a double-stranded-RNA trigger. Here we show that Tudor-SN (tudor staphylococcal nuclease)--a protein containing five staphylococcal/micrococcal nuclease domains and a tudor domain--is a component of the RISC enzyme in Caenorhabditis elegans, Drosophila and mammals. Although Tudor-SN contains non-canonical active-site sequences, we show that purified Tudor-SN exhibits nuclease activity similar to that of other staphylococcal nucleases. Notably, both purified Tudor-SN and RISC are inhibited by a specific competitive inhibitor of micrococcal nuclease. Tudor-SN is the first RISC subunit to be identified that contains a recognizable nuclease domain, and could therefore contribute to the RNA degradation observed in RNAi.     

The matches,achieved by natural selection,between biological capacities and their natural loads

Natural selection tends to eliminate unutilized capacities because of their costs. Hence we ask how large are the reserve capacities by which biological capacities exceed natural loads, and how closely are related biological capacities matched to each other. Measured capacities (V_max values) of small intestinal brush-border nutrient transporters are typically around twice their natural loads (dietary intakes of their substrates); the ratio is higher for a transporter of a hyperessential nutrient. Preliminary evidence suggests matching of capacities between different steps in carbohydrate metabolism, and between the intestine, liver, kidneys, and spleen. Symmorphosis — the postulated matching of capacities to each other and to loads — is a testable hypothesis of economic design, useful in detecting and explaining cases of apparently uneconomic design.     

Photoperiodically induced delayed insect metamorphosis: a larval oligopause inDiatraea saccharalis

Summary Sugarcane borers enter a state of delayed metamorphosis when exposed to a 12-h photophase at 21°C. Larval feeding, growth, and molting continues but pupation is suppressed under these conditions.     

Assessing high compositional differences of beetle assemblages across vertical woodland strata in the New Forest,Hampshire, England

Closed-canopy woodlands are complex ecosystems with strong vertical environmental stratification. The degree to which this vertical stratification has led to compartmentalisation in invertebrate assemblages in temperate woodlands has been researched to a limited extent, yet there are still gaps in our understanding. Here, we used five different sampling methods to sample beetles across vertical strata of nine woodland sites in the New Forest National Park, Hampshire, England. The sampling methods yielded 2412 individuals across 157 species, of which 46 were significant indicator species for one stratum or a combination of strata. Multivariate analysis of composition showed a strong separation at a subfamily level between strata, with many only found in a single stratum. This suggests a strongly compartmentalised vertical stratification of the beetle assemblages at both species and higher taxonomic levels. Our results display that multiple strata need to be sampled to obtain true estimates of overall beetle species richness in woodlands and forests. Limitations in using a single sampling method and biases using mixed sampling method protocols across a vertical transect are also discussed.     

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.