Rybp interacts with Hippi and enhances Hippi-mediated apoptosis

Rybp (DEDAF) has been shown to interact with DED-containing proteins and to encode pro-apoptotic functions. Here we characterize a novel interaction between Rybp and Hippi, a protein implicated in neuronal apoptosis as well as in the pathogenesis of Huntington’s disease. Rybp can synergize with Hippi to enhance Caspase 8-mediated apoptosis and also appears to be essential for Hippi-mediated apoptosis. Moreover, Rybp may mediate or regulate the interaction between Hippi and Caspase 8. Finally, Rybp and Hippi co-localize in a subset of neurons in the developing mouse brain. Together, these findings suggest that Rybp and Hippi may functionally interact in the apoptotic processes that accompany normal murine neural development.     

Stoichiometric patterns in foliar nutrient resorption across multiple scales

? Nutrient resorption is a fundamental process through which plants withdraw nutrients from leaves before abscission. Nutrient resorption patterns have the potential to reflect gradients in plant nutrient limitation and to affect a suite of terrestrial ecosystem functions. ? Here, we used a stoichiometric approach to assess patterns in foliar resorption at a variety of scales, specifically exploring how N?:?P resorption ratios relate to presumed variation in N and/or P limitation and possible relationships between N?:?P resorption ratios and soil nutrient availability. ? N?:?P resorption ratios varied significantly at the global scale, increasing with latitude and decreasing with mean annual temperature and precipitation. In general, tropical sites (absolute latitudes 相似文献   

Host invasion by Batrachochytrium dendrobatidis: fungal and epidermal ultrastructure in model anurans

The chytridiomycete fungus Batrachochytrium dendrobatidis (Bd) colonizes mouthparts of amphibian larvae and superficial epidermis of post-metamorphic amphibians, causing the disease chytridiomycosis. Fungal growth within host cells has been documented by light and transmission electron microscopy; however, entry of the fungus into host cells has not. Our objective was to document how Bd enters host cells in the wood frog Lithobates sylvaticus, a species at high mortality risk for chytridiomycosis, and the bullfrog L. catesbeianus, a species at low mortality risk for chytridiomycosis. We inoculated frogs and documented infection with transmission electron microscopy. Zoospores encysted on the skin surface and produced morphologically similar germination tubes in both host species that penetrated host cell membranes and enabled transfer of zoospore contents into host cells. Documenting fungal and epidermal ultrastructure during host invasion furthers our understanding of Bd development and the pathogenesis of chytridiomycosis.     

Visibility of the urethral meatus and risk of urinary tract infections in uncircumcised boys

Background:

Uncircumcised boys are at higher risk for urinary tract infections than circumcised boys. Whether this risk varies with the visibility of the urethral meatus is not known. Our aim was to determine whether there is a hierarchy of risk among uncircumcised boys whose urethral meatuses are visible to differing degrees.

Methods:

We conducted a prospective cross-sectional study in one pediatric emergency department. We screened 440 circumcised and uncircumcised boys. Of these, 393 boys who were not toilet trained and for whom the treating physician had requested a catheter urine culture were included in our analysis. At the time of catheter insertion, a nurse characterized the visibility of the urethral meatus (phimosis) using a 3-point scale (completely visible, partially visible or nonvisible). Our primary outcome was urinary tract infection, and our primary exposure variable was the degree of phimosis: completely visible versus partially or nonvisible urethral meatus.

Results:

Cultures grew from urine samples from 30.0% of uncircumcised boys with a completely visible meatus, and from 23.8% of those with a partially or nonvisible meatus (p = 0.4). The unadjusted odds ratio (OR) for culture growth was 0.73 (95% confidence interval [CI] 0.35–1.52), and the adjusted OR was 0.41 (95% CI 0.17–0.95). Of the boys who were circumcised, 4.8% had urinary tract infections, which was significantly lower than the rate among uncircumcised boys with a completely visible urethral meatus (unadjusted OR 0.12 [95% CI 0.04–0.39], adjusted OR 0.07 [95% CI 0.02–0.26]).

Interpretation:

We did not see variation in the risk of urinary tract infection with the visibility of the urethral meatus among uncircumcised boys. Compared with circumcised boys, we saw a higher risk of urinary tract infection in uncircumcised boys, irrespective of urethral visibility.Urinary tract infections are one of the most common serious bacterial infections in young children.^1–6 Prompt diagnosis is important, because children with urinary tract infection are at risk for bacteremia⁶ and renal scarring.^1,7 Uncircumcised boys have a much higher risk of urinary tract infection than circumcised boys,^{1,3,4,6,8–12} likely as a result of heavier colonization under the foreskin with pathogenic bacteria, which leads to ascending infections.^13,14 The American Academy of Pediatrics recently suggested that circumcision status be used to select which boys should be evaluated for urinary tract infection.¹ However, whether all uncircumcised boys are at equal risk for infection, or whether the risk varies with the visibility of the urethral opening, is not known. It has been suggested that a subset of uncircumcised boys with a poorly visible urethral opening are at increased risk of urinary tract infection,^15–17 leading some experts to consider giving children with tight foreskins topical cortisone or circumcision to prevent urinary tract infections.^13,18–21We designed a study to challenge the opinion that all uncircumcised boys are at increased risk for urinary tract infections. We hypothesized a hierarchy of risk among uncircumcised boys depending on the visibility of the urethral meatus, with those with a partially or nonvisible meatus at highest risk, and those with a completely visible meatus having a level of risk similar to that of boys who have been circumcised. Our primary aim was to compare the proportions of urinary tract infections among uncircumcised boys with a completely visible meatus with those with a partially or nonvisible meatus.     

Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf

Legionella pneumophila is an intracellular bacterium that causes an acute form of pneumonia called Legionnaires' disease. After infection of human macrophages, the Legionella-containing phagosome (LCP) avoids fusion with the lysosome allowing intracellular replication of the bacterium. In macrophages derived from most mouse strains, the LCP is delivered to the lysosome resulting in Legionella degradation and restricted bacterial growth. Mouse macrophages lacking the NLR protein Ipaf or its downstream effector caspase-1 are permissive to intracellular Legionella replication. However, the mechanism by which Ipaf restricts Legionella replication is not well understood. Here we demonstrate that the presence of flagellin and a competent type IV secretion system are critical for Legionella to activate caspase-1 in macrophages. Activation of caspase-1 in response to Legionella infection also required host Ipaf, but not TLR5. In the absence of Ipaf or caspase-1 activation, the LCP acquired endoplasmic reticulum-derived vesicles, avoided fusion with the lysosome, and allowed Legionella replication. Accordingly a Legionella mutant lacking flagellin did not activate caspase-1, avoided degradation, and replicated in wild-type macrophages. The regulation of phagosome maturation by Ipaf occurred within 2 h after infection and was independent of macrophage cell death. In vivo studies confirmed that flagellin and Ipaf play an important role in the control of Legionella clearance. These results reveal that Ipaf restricts Legionella replication through the regulation of phagosome maturation, providing a novel function for NLR proteins in host defense against an intracellular bacterium.     

Immune responses to an encapsulated allogeneic islet beta-cell line in diabetic NOD mice

Our goal is to develop effective islet grafts for treating type 1 diabetes. Since human islets are scarce, we evaluated the efficacy of a microencapsulated insulin-secreting conditionally transformed allogeneic β-cell line (βTC-tet) in non-obese diabetic mice treated with tetracycline to inhibit cell growth. Relatively low serum levels of tetracycline controlled proliferation of βTC-tet cells without inhibiting effective control of hyperglycemia in recipients. There was no significant host cellular reaction to the allografts or host cell adherence to microcapsules, and host cytokine levels were similar to those of sham-operated controls. We conclude that encapsulated allogeneic β-cell lines may be clinically relevant, because they effectively restore euglycemia and do not elicit a strong cellular immune response following transplantation. To our knowledge, this is the first extensive characterization of the kinetics of host cellular and cytokine responses to an encapsulated islet cell line in an animal model of type 1 diabetes.     

Rich Pickings Near Large Communal Roosts Favor ‘Gang’ Foraging by Juvenile Common Ravens,Corvus corax

Ravens (Corvus corax) feed primarily on rich but ephemeral carcasses of large animals, which are usually defended by territorial pairs of adults. Non-breeding juveniles forage socially and aggregate in communal winter roosts, and these appear to function as ‘information centers’ regarding the location of the rare food bonanzas: individuals search independently of one another and pool their effort by recruiting each other at roosts. However, at a large raven roost in Newborough on Anglesey, North Wales, some juveniles have been observed recently to forage in ‘gangs’ and to roost separately from other birds. Here we adapt a general model of juvenile common raven foraging behavior where, in addition to the typical co-operative foraging strategy, such gang foraging behavior could be evolutionarily stable near winter raven roosts. We refocus the model on the conditions under which this newly documented, yet theoretically anticipated, gang-based foraging has been observed. In the process, we show formally how the trade off between search efficiency and social opportunity can account for the existence of the alternative social foraging tactics that have been observed in this species. This work serves to highlight a number of fruitful avenues for future research, both from a theoretical and empirical perspective.     

Functional shifts in unvegetated,perhumid, recently-deglaciated soils do not correlate with shifts in soil bacterial community composition

Past work in recently deglaciated soils demonstrates that microbial communities undergo shifts prior to plant colonization. To date, most studies have focused on relatively ‘long’ chronosequences with the ability to sample plant-free sites over at least 50 years of development. However, some recently deglaciated soils feature rapid plant colonization and questions remain about the relative rate of change in the microbial community in the unvegetated soils of these chronosequences. Thus, we investigated the forelands of the Mendenhall Glacier near Juneau, AK, USA, where plants rapidly establish. We collected unvegetated samples representing soils that had been ice-free for 0, 1, 4, and 8 years. Total nitrogen (N) ranged from 0.00∼0.14 mg/g soil, soil organic carbon pools ranged from 0.6∼2.3 mg/g soil, and both decreased in concentration between the 0 and 4 yr soils. Biologically available phosphorus (P) and pH underwent similar dynamics. However, both pH and available P increased in the 8 yr soils. Nitrogen fixation was nearly undetectable in the most recently exposed soils, and increased in the 8 yr soils to ∼5 ng N fixed/cm²/h, a trend that was matched by the activity of the soil N-cycling enzymes urease and β-l,4-N-acetyl-glucosa-minidase. 16S rRNA gene clone libraries revealed no significant differences between the 0 and 8 yr soils; however, 8 yr soils featured the presence of cyanobacteria, a division wholly absent from the 0 yr soils. Taken together, our results suggest that microbes are consuming allochtonous organic matter sources in the most recently exposed soils. Once this carbon source is depleted, a competitive advantage may be ceded to microbes not reliant on in situ nutrient sources.     

Antioxidants decreases the intensification of low density lipoprotein in vivo peroxidation during therapy with statins

The oxidative modification of low density lipoprotein (LDL) is thought to play an important role in atherogenesis. Drugs of -hydroxy--methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) family are usually used as a very effective lipid-lowering preparations but they simultaneously block biosynthesis of both cholesterol and ubiquinone Q₁₀ (coenzyme Q), which is an intermediate electron carrier in the mitochondrial respiratory chain. It is known that reduced form of ubiquinone Q₁₀ acts in the human LDL as very effective natural antioxidant. Daily per os administration of HMG-CoA reductase inhibitor simvastatin to rats for 30 day had no effect on high-energy phosphates (adenosin triphosphate, creatine phosphate) content in liver but decreased a level of these substances in myocardium. We study the Cu²⁺-mediated susceptibility of human LDL to oxidation and the levels of free radical products of LDL lipoperoxidation in LDL particles from patients with atherosclerosis after 3 months treatment with natural antioxidants vitamin E as well as during 6 months administration of HMG-CoA reductase inhibitors such as pravastatin and cerivastatin in monotherapy and in combination with natural antioxidant ubiquinone Q₁₀ or synthetic antioxidant probucol in a double-blind placebo-controlled trials. The 3 months of natural antioxidant vitamin E administration (400 mg daily) to patients did not increase the susceptibility of LDL to oxidation. On the other hand, synthetic antioxidant probucol during long-time period of treatment (3–6 months) in low-dose (250 mg daily) doesn't change the lipid metabolism parameters in the blood of patients but their high antioxidant activity was observed. Really, after oxidation of probucol-contained LDL by C-15 animal lipoxygenase in these particles we identified the electron spin resonance signal of probucol phenoxyl radical that suggests the interaction of LDL-associated probucol with lipid radicals in vivo. We observed that 6 months treatment of patients with pravastatine (40 mg daily) or cerivastatin (0.4 mg daily) was followed by sufficiently accumulation of LDL lipoperoxides in vivo. In contrast, the 6 months therapy with pravastatin in combination with ubiquinone Q₁₀ (60 mg daily) sharply decreased the LDL initial lipoperoxides level whereas during treatment with cerivastatin in combination with probucol (250 mg daily) the LDL lipoperoxides concentration was maintained on an invariable level. Therefore, antioxidants may be very effective in the prevention of atherogenic oxidative modification of LDL during HMG-CoA reductase inhibitors therapy.