Genetic ablation of caveolin-2 sensitizes mice to bleomycin-induced injury

Caveolar domains act as platforms for the organization of molecular complexes involved in signal transduction. Caveolin proteins, the principal structural components of caveolae, have been involved in many cellular processes. Caveolin-1 (Cav-1) and caveolin-2 (Cav-2) are highly expressed in the lung. Cav-1-deficient mice (Cav-1^−/−) and Cav-2-deficient mice (Cav-2^−/−) exhibit severe lung dysfunction attributed to a lack of Cav-2 expression. Recently, Cav-1 has been shown to regulate lung fibrosis in different models. Here, we show that Cav-2 is also involved in modulation of the fibrotic response, but through distinct mechanisms. Treatment of wild-type mice with the pulmonary fibrosis-inducer bleomycin reduced the expression of Cav-2 and its phosphorylation at tyrosine 19. Importantly, Cav-2^−/− mice, but not Cav-1^−/− mice, were more sensitive to bleomycin-induced lung injury in comparison to wild-type mice. Bleomycin-induced lung injury was characterized by alveolar thickening, increase in cell density, and extracellular matrix deposition. The lung injury observed in bleomycin-treated Cav-2^−/− mice was not associated with alterations in the TGF-β signaling pathway and/or in the ability to produce collagen. However, apoptosis and proliferation were more prominent in lungs of bleomycin-treated Cav-2^−/− mice. Since Cav-1^−/− mice also lack Cav-2 expression and show a different outcome after bleomycin treatment, we conclude that Cav-1 and Cav-2 have distinct roles in bleomycin induced-lung fibrosis, and that the balance of both proteins determines the development of the fibrotic process.     

Genetic linkage analysis of the murine developmental mutant velvet coat (Ve) and the distal chromosome 15 developmental genes Hox-3.1, Rar-g, Wnt-1, and Krt-2.

We have identified restriction fragment length polymorphisms between Mus musculus and Mus spretus for the Chromosome 15 loci Hox-3, Wnt-1, Krt-2, Rar-g, and Ly-6. We followed the inheritance of these alleles in interspecific genetic test crosses between velvet coat (Ve) heterozygotes and M. spretus. The results suggest a gene order and recombination distances (in cM) of Ly-6-22-Wnt-1-2-Ve/Krt-2/Rar-g-3-Hox-3. No recombination was found between Ve, Krt-2, and Rar-g. The data also provide evidence for the hypothesis of a large-scale genomic duplication involving homologous gene pairs on mouse Chromosomes 15 and 11.     

Improved processes for the production and isolation of dynemicin A and large-scale fermentation in a 10000-liter fermentor

Summary Supplementing the culture ofMicromonospora chersina sp. nov. No. M956-1 with NaI (0.5 mg/l) enhanced the production of dynemicin A by 35-fold in shake flask culture. Homogeneous dynemicin A was obtained from the whole broth extract by Dicalite chromatography, Sephadex LH-20 chromatography and vacuum liquid chromatography. Gram quantities of dynemicin A were obtained from the fermentation ofM. chersina sp. nov. No. M956-1 in a 10000-liter fermentor.     

A leucine----proline mutation in the H1 subdomain of keratin 1 causes epidermolytic hyperkeratosis.

Epidermolytic hyperkeratosis is an autosomal dominant disorder affecting the structural integrity of the suprabasal layers of human epidermis. We have recently documented in one family linkage of the disease phenotype to the cluster of type II keratins. We have now identified a leucine----proline amino acid substitution in the conserved H1 subdomain of keratin 1 that is present only in affected family members. Using a quantitative assay and electron microscopy with synthetic peptides, we show that, whereas the wild-type H1 peptide rapidly disassembles preformed keratin filaments in vitro, the mutant peptide does this far less efficiently. Therefore the mutation in keratin 1 is likely to cause defective keratin filaments and hence a defective cytoskeleton in the epidermal cells in vivo.     

Two distinct conformational states define the interaction of human RAD51‐ATP with single‐stranded DNA

An essential mechanism for repairing DNA double‐strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein filament on single‐stranded DNA, promoting DNA‐strand exchange. Here, we study the interaction of hRAD51 with single‐stranded DNA using a single‐molecule approach. We show that ATP‐bound hRAD51 filaments can exist in two different states with different contour lengths and with a free‐energy difference of ~4 k_BT per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly‐competent ADP‐bound configuration. In agreement with the single‐molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51‐ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51‐ATP filaments can exist in two interconvertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange.     

Convergent evolution of agaonine and sycoecine (Agaonidae, Chalcidoidea) head shape in response to the constraints of host fig morphology

Abstract. Similar morphological adaptations have arisen independently across separate lineages within the fig wasps (Agaonidae, Chalcidoidea, Hymenoptera) in response to the extreme selective pressure provided by the morphological constraints of their host fig trees ( Ficus , Moraceae). Evidence is forwarded that supports the convergence of female head shape between two distinct fig wasp lineages, the Agaoninae (pollinators) and Sycoecinae (non-pollinators), utilizing the same host Ficus species (section Gagolychia ). In contrast to the vast majority of the non-pollinating fig wasps, that oviposit from the outside of the fig, the Agaoninae and Sycoecinae must negotiate the fig ostiole for internal oviposition, with the result that these independent lineages are simultaneously exposed to the selective pressure imposed by ostiolar morphology. Selection will favour a head shape that facilitates successful penetration of the fig cavity and this has resulted in the evolution of similar head shapes in the two lineages. Female head shape in both subfamilies was found to correlate with fig size, with elongate heads associated with large fig size. Given that ostiole bract arrangement is uniform within section Galoglychia , it appears that ostiole length may be the main factor contributing to head shape determination. The high degree of co-adaptation of head shape suggests that both the Sycoecinae and Agaoninae have coevolved with their host Ficus species.     

Alternative mating tactics and extreme male dimorphism in fig wasps

The dimorphisms in morphology and behaviour of male fig wasps are among the most extreme in the animal kingdom, and offer excellent opportunities to test the predictions of certain sexual selection models. Winged males resemble their conspecific females closely, but wingless males are so divergent in form that they have repeatedly been classified into different taxa. Wingless males mate within their natal fig fruits, whereas winged males disperse to mate. Individual species may have winged males, wingless males or both morphs. A key hypothesis proposes that sexual selection on male mating opportunities favours winged males in species with small broods and wingless males in species with large broods. Using data from 114 species in 33 genera, we show that both simple and formal comparative analyses support the correlated evolution of large brood size and male winglessness. Theoretical models further predict that, in male dimorphic species, the proportion of winged males should equal (in cases without local mate competition) or exceed (in cases with local mate competition) the proportion of females developing in fig fruits without wingless males. These predictions are met by eight out of nine male dimorphic species studied. Taken together, the patterns across all species, and between different male dimorphic species, strongly support sexual selection on mating opportunities as the major determinant of male morph ratios in fig wasps.