p110γ/δ Double-Deficiency Induces Eosinophilia and IgE Production but Protects from OVA-Induced Airway Inflammation

The catalytical isoforms p110γ and p110δ of phosphatidylinositide 3-kinase γ (PI3Kγ) and PI3Kδ play an important role in the pathogenesis of asthma. Two key elements in allergic asthma are increased levels of eosinophils and IgE. Dual pharmacological inhibition of p110γ and p110δ reduces asthma-associated eosinophilic lung infiltration and ameliorates disease symptoms, whereas the absence of enzymatic activity in p110γ^KOδ^D910A mice increases IgE and basal eosinophil counts. This suggests that long-term inhibition of p110γ and p110δ might exacerbate asthma. Here, we analysed mice genetically deficient for both catalytical subunits (p110γ/δ^-/-) and determined basal IgE and eosinophil levels and the immune response to ovalbumin-induced asthma. Serum concentrations of IgE, IL-5 and eosinophil numbers were significantly increased in p110γ/δ^-/- mice compared to single knock-out and wildtype mice. However, p110γ/δ^-/- mice were protected against OVA-induced infiltration of eosinophils, neutrophils, T and B cells into lung tissue and bronchoalveolar space. Moreover, p110γ/δ^-/- mice, but not single knock-out mice, showed a reduced bronchial hyperresponsiveness. We conclude that increased levels of eosinophils and IgE in p110γ/δ^-/- mice do not abolish the protective effect of p110γ/δ-deficiency against OVA-induced allergic airway inflammation.     

Land use,fallow period and the recovery of a Caatinga forest

Caatinga vegetation continues to be converted into mosaics of secondary forest stands, but the affect of this process on biodiversity has not yet been examined. We used 35 regenerating and old‐growth stands of Caatinga to examine the recovery of plant assemblages subsequent to slash‐and‐burn agriculture and cattle ranching/pasture in northeastern Brazil. Plant assemblages were contrasted in terms of community structure (stem density/basal area/species richness/diversity), functional (leaf habit/reproductive traits) and taxonomic composition. Soil attributes were also examined to infer potential drivers for cross‐habitat differences. As expected, plant assemblages clearly differed across a large set of community‐level attributes, including all trait categories relative to leaf habit and reproduction (pollination syndrome/floral color, size, type). Overall, old‐growth forest stands supported distinct and more diverse assemblages at the plot and habitat level; e.g., long‐lived tree species were almost exclusively found in old‐growth forest stands. For most attributes, plant assemblages subsequent to pasture exhibited intermediate values between those exhibited by old‐growth forest and those of agriculture‐related stands. Surprisingly, soils exhibited similar fertility‐related scores across habitats. Our results indicate that: (1) sprouting/resprouting represents an important mechanism of forest regeneration; (2) assemblage‐level attributes suggest recovery at distinct rates; (3) forest regeneration implies community‐level changes in both vegetative and reproductive functional attributes, including directional changes; (4) Caatinga is not able to completely recover in a period of 15‐yr following land abandonment; and (5) historical land use affects recovery rates and successional pathways/taxonomic trajectories. Seasonally dry tropical forests may intrinsically cover a wide range of patterns relative to successional model, recovery rates and successional pathways.     

Cyclic expression of the voltage‐gated potassium channel KV10.1 promotes disassembly of the primary cilium

The primary cilium, critical for morphogenic and growth factor signaling, is assembled upon cell cycle exit, but the links between ciliogenesis and cell cycle progression are unclear. K_V10.1 is a voltage‐gated potassium channel frequently overexpressed in tumors. We have previously reported that expression of K_V10.1 is temporally restricted to a time period immediately prior to mitosis in healthy cells. Here, we provide microscopical and biochemical evidence that K_V10.1 localizes to the centrosome and the primary cilium and promotes ciliary disassembly. Interference with K_V10.1 ciliary localization abolishes not only the effects on ciliary disassembly, but also K_V10.1‐induced tumor progression in vivo. Conversely, upon knockdown of K_V10.1, ciliary disassembly is impaired, proliferation is delayed, and proliferating cells show prominent primary cilia. Thus, modulation of ciliogenesis by K_V10.1 can explain the influence of K_V10.1 expression on the proliferation of normal cells and is likely to be a major mechanism underlying its tumorigenic effects.     

Effects of thermal water inhalation in chronic upper respiratory tract infections in elderly and young patients

Background

Chronic upper respiratory tract infections (cURTI) are very frequent illnesses which occur at any age of life. In elderly, cURTI are complicated by immunosenescence, with involvement of lung immune responsiveness.

Results

In the present study, 51 elderly (age range: 66–86) and 51 young (age range 24–58) cURTI patients underwent a single cycle (two weeks) of inhalatory therapy with salt-bromide-iodine thermal water in the thermal station “Margherita di Savoia” (Margherita di Savoia, BAT, Italy). Peripheral blood serum cytokines and clinical assessment were performed before therapy (T0) and after six months (T1) and 12 months (T2) from inhalatory treatment. In both elderly and young patients, at baseline an increased release of T helper (h)1-related cytokines [interleukin (IL)-2 and interferon-γ] and of Th2-related cytokine (IL-4) was documented. Inhalatory treatment reduced the excessive secretion of all the above-cited cytokines. IL-10 values were above normality at all times considered in both groups of patients. In addition, an increase in IL-17 and IL-21 serum levels following therapy was observed in both groups of patients. Pro-inflammatory cytokine (IL-1β, IL-6, IL-8 and tumor necrosis factor-α) baseline values were lower than normal values at T0 in both elderly and young cURTI patients. Their levels increased following inhalatory treatment.Clinically, at T2 a dramatic reduction of frequency of upper respiratory tract infections was recorded in both groups of patients.

Conclusion

Thermal water inhalation is able to modulate systemic immune response in elderly and young cURTI patients, thus reducing excessive production of Th1 and Th2-related cytokines, on the one hand. On the other hand, increased levels of IL-21 (an inducer of Th17 cells) and of IL-17 may be interpreted as a protective mechanism, which likely leads to neutrophil recruitment in cURTI patients. Also restoration of pro-inflammatory cytokine release following inhalatory therapy may result in microbe eradication. Quite importantly, the maintenance of high levels of IL-10 during the follow-up would suggest a consistent regulatory role of this cytokine in attenuating the pro-inflammatory arm of the immune response.

     

Identification of Polymorphisms in the Rabbit Growth Hormone Receptor (GHR) Gene and Association with Finishing Weight in a Commercial Meat Rabbit Line

A shortcut to identify DNA markers associated with economic traits is to use a candidate gene approach that is still useful in livestock species in which molecular tools and resources are not advanced or not well developed. Mutations in the growth hormone receptor (GHR) gene associated with production traits have been already described in several livestock species. For this reason GHR could be an interesting candidate gene in the rabbit. In this study we re-sequenced all exons and non-coding regions of the rabbit GHR gene in a panel of 10 different rabbits and identified 10 single nucleotide polymorphisms (SNPs). One of them (g.63453192C>G or c.106C>G), located in exon 3 was a missense mutation (p.L36V) substituting an amino acid in a highly conserved position across all mammals. This mutation was genotyped in 297 performance tested rabbits of a meat male line and association analysis showed that the investigated SNP was associated with weight at 70 days (P < 0.05). The most frequent genotype (GG) was in animals with higher weight at this age, suggesting that the high directional selection pressure toward this trait since the constitution of the genotyped line might have contributed to shape allele frequencies at this polymorphic site.