Host-selective toxins produced by <Emphasis Type="Italic">Stagonospora nodorum</Emphasis> confer disease susceptibility in adult wheat plants under field conditions

Stagonospora nodorum, causal agent of Stagonospora nodorum blotch (SNB), is a destructive pathogen of wheat worldwide. As is true for many necrotrophic host–pathogen systems, the wheat-S. nodorum system is complex and resistance to SNB is usually quantitatively inherited. We recently showed that S. nodorum produces at least four proteinaceous host-selective toxins that interact with dominant host sensitivity/susceptibility gene products to induce SNB in seedlings. Here, we evaluated a population of wheat recombinant inbred lines that segregates for Tsn1, Snn2, and Snn3, which confer sensitivity to the toxins SnToxA, SnTox2, and SnTox3, respectively, to determine if compatible host–toxin interactions are associated with adult plant susceptibility to SNB foliar disease under field conditions. Artificial inoculation of the population in 2 years and two locations with a fungal isolate known to produce SnToxA and SnTox2 indicated that compatible SnToxA–Tsn1 and SnTox2–Snn2 interactions accounted for as much as 18 and 15% of the variation in disease severity on the flag leaf, respectively. As previously reported for seedlings, the effects of these two interactions in conferring adult plant susceptibility were largely additive. Additional adult plant resistance QTLs were identified on chromosomes 1B, 4B, and 5A, of which, the 1B and 5A QTLs were previously reported to be associated with seedling resistance to SNB. Therefore, in this population, some of the same QTLs are responsible for seedling and adult plant resistance/susceptibility. This is the first report showing that host-selective toxins confer susceptibility of adult plants to SNB, further substantiating the importance of compatible toxin–host interactions in the wheat-S. nodorum pathosystem. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture.     

The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy

RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNFalpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies.     

Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin

Normal cellular functions of hamartin and tuberin, encoded by the TSC1 and TSC2 tumor suppressor genes, are closely related to their direct interactions. However, the regulation of the hamartin-tuberin complex in the context of the physiologic role as tumor suppressor genes has not been documented. Here we show that insulin or insulin growth factor (IGF) 1 stimulates phosphorylation of tuberin, which is inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 but not by the mitogen-activated protein kinase inhibitor PD98059. Expression of constitutively active PI3K or active Akt, including Akt1 and Akt2, induces tuberin phosphorylation. We further demonstrate that Akt/PKB associates with hamartin-tuberin complexes, promoting phosphorylation of tuberin and increased degradation of hamartin-tuberin complexes. The ability to form complexes, however, is not blocked. Akt also inhibits tuberin-mediated degradation of p27(kip1), thereby promoting CDK2 activity and cellular proliferation. Our results indicate that tuberin is a direct physiological substrate of Akt and that phosphorylation of tuberin by PI3K/Akt is a major mechanism controlling hamartin-tuberin function.     

Nonequilibrium dynamics of social groups: insights from foraging Argentine ants

Summary We studied disturbance patterns in groups of feeding Argentine ants, Linepithema humile. All disturbances were caused by the ants themselves, without application of exogenous disturbances. The overall pattern, which consisted of a power law distribution of disturbance avalanche sizes, each of which was initiated by a single wandering ant, is similar to patterns characteristic of self-organized critical systems. In addition, we observed variation among individuals in response to disturbance according to their level of satiation. Ants with distended gasters (indicative of volume of food uptake) resumed feeding less rapidly than their thinner counterparts, and were more likely to leave food sources altogether. Although these disturbances reduce food collection because feeding ants are interrupted, they are minimal and may enable ant groups to balance collectively the advantage of rapid alarm communication with the costs of interrupted foraging from trivial disturbances.Received 18 September 2003; revised 21 November 2003; accepted 4 December 2003.     

Mental status of females with an FMR1 gene full mutation.

The cloning of the FMR1 gene enables molecular diagnosis in patients and in carriers (male and female) of this X-linked mental retardation disorder. Unlike most X-linked disorders, a considerable proportion of the female carriers of a full mutation of the FMR1 gene is affected. In this study, the intelligence quotients (IQs) were ascertained by the Wechsler Adult Intelligence Scale in 33 adult females with a full mutation, with 28 first-degree adult female relatives (mainly sisters) without a full mutation as controls. Seventy-one percent of the females with a full mutation had IQ scores below 85. In paired analysis, no significant correlation could be detected between the IQs of the females with a full mutation and those of their first-degree female relatives, reflecting a dominant effect of the FMR1 gene full mutation in the mental development of females. Considering females with a full mutation only, we observed a significant relation between the proportion of normal FMR1 alleles on the active X chromosome and IQ. We present a model to explain this relationship.     

New polymorphic DNA marker close to the fragile site FRAXA

DNA from a human-hamster hybrid cell line, 908-K1B17, containing a small terminal portion of the long arm of the human X chromosome as well as the pericentric region of 19q was used as starting material for the isolation of an X-chromosome-specific DNA segment, RN1 (DXS369), which identifies a XmnI RFLP. Linkage analysis in fragile X families resulted in a maximum lod score of 15.3 at a recombination fraction of 0.05 between RN1 and fra(X). Analysis of recombinations around the fra(X) and distal to DXS105. Analysis of the marker content of hybrid cell line 908K1B17 suggests the localization of RN1 between DXS98 and fra(X). Heterozygosity of DXS369 is approximately 50%, which extends the diagnostic potential of RFLP analysis in fragile X families significantly.     

Regional localization of a beta-galactosidase locus on human chromosome 22.

Human white blood cells with an X/22 translocation [46, XX, t(X;22)(q23;q13)] were fused with Chinese hamster cells. The isolated hybrids were analyzed for human chromosomes and 21 enzyme markers. An electrophoretic technique for studying the beta-galactosidase isoenzymes in man-Chinese hamster hybrid cells was developed. Immunological studies showed that the beta-galactosidase marker studied in these hybrids did contain immunological determinants of human origin. Furthermore the results provided evidence that a locus for beta-galactosidase is situated on chromosome 22 distal to the breakpoint in q13.     

Functional significance of alpha-stimulation and alpha-blockade on responses to cardiac nerve stimulation in anesthetized dogs

Experiments were conducted to determine if α-stimulants could inhibit responses to sympathetic nerve stimulation $\text{via}$ a feedback inhibition loop mediated by prejunctional α-receptors. Responses to cardiac nerve stimulation in anesthetized dogs were compared before, during the peak effect of a drug infusion, and during a second drug infusion subsequent to the administration of phentolamine (5 mg/kg i.v.). The drugs infused were norepinephrine, phenylephrine, clonidine, naphazoline - all α-stimulants - and guanethidine. All drugs caused marked elevations of blood pressure, an indication of α-stimulation, but only guanethidine caused significant blockade of responses to sympathetic nerve stimulation. In addition, phentolamine, an α-receptor blocker, and desipramine, an inhibitor of amine uptake, did not potentiate responses to sympathetic nerve stimulation. These results do not support the hypothesis that sympathetic nerves are under a functionally significant feedback loop mediated by α-receptors.     

Parameter drift stabilizes long-range extinction forecasts

Estimates of the reliability of population viability analysis (PVA), accounting for uncertainties in model parameters, often arrive at confidence intervals for extinction probability so wide as to be almost meaningless. This lack of precision is a consequence of extreme sensitivity to average linear growth rate, when predicting to a distant time horizon. Longer‐term trends or drift in parameter values (a form of ‘reddened’ environmental variability) will also affect the accuracy of such forecasts. This letter reports how, contrary to intuition, introducing such a component of variability may improve the precision of extinction forecasts. The paradoxical result arises because the dependence of extinction probability on growth rate is weakened, and shifted onto other parameters (e.g. diffusion strength) where dependence is less sensitive. This offers hope that, with reasonable knowledge of environmental stochasticity, it may still be meaningful to carry out longer range PVAs.