T1alpha,a lung type I cell differentiation gene,is required for normal lung cell proliferation and alveolus formation at birth

T1alpha, a differentiation gene of lung alveolar epithelial type I cells, is developmentally regulated and encodes an apical membrane protein of unknown function. Morphological differentiation of type I cells to form the air-blood barrier starts in the last few days of gestation and continues postnatally. Although T1alpha is expressed in the foregut endoderm before the lung buds, T1alpha mRNA and protein levels increase substantially in late fetuses when expression is restricted to alveolar type I cells. We generated T1alpha null mutant mice to study the role of T1alpha in lung development and differentiation and to gain insight into its potential function. Homozygous null mice die at birth of respiratory failure, and their lungs cannot be inflated to normal volumes. Distal lung morphology is altered. In the absence of T1alpha protein, type I cell differentiation is blocked, as indicated by smaller airspaces, many fewer attenuated type I cells, and reduced levels of aquaporin-5 mRNA and protein, a type I cell water channel. Abundant secreted surfactant in the narrowed airspaces, normal levels of surfactant protein mRNAs, and normal patterns and numbers of cells expressing surfactant protein-B suggest that differentiation of type II cells, also alveolar epithelial cells, is normal. Anomalous proliferation of the mesenchyme and epithelium at birth with unchanged numbers of apoptotic cells suggests that loss of T1alpha and/or abnormal morphogenesis of type I cells alter the proliferation rate of distal lung cells, probably by disruption of epithelial-mesenchymal signaling.     

Mammals evolve faster on smaller islands

Island mammals often display remarkable evolutionary changes in size and morphology. Both theory and empirical data support the hypothesis that island mammals evolve at faster rates than their mainland congeners. It is also often assumed that the island effect is stronger and that evolution is faster on the smallest islands. I used a dataset assembled from the literature to test these assumptions for the first time. I show that mammals on smaller islands do indeed evolve more rapidly than mammals on larger islands, and also evolve by a greater amount. These results fit well the theory of an evolutionary burst due to the opening of new ecological opportunities on islands. This evolutionary burst is expected to be the strongest on the smallest islands where the contrast between the island and the mainland environments is the most dramatic.     

Morphological evolution is accelerated among island mammals

Dramatic evolutionary changes occur in species isolated on islands, but it is not known if the rate of evolution is accelerated on islands relative to the mainland. Based on an extensive review of the literature, I used the fossil record combined with data from living species to test the hypothesis of an accelerated morphological evolution among island mammals. I demonstrate that rates of morphological evolution are significantly greater—up to a factor of 3.1—for islands than for mainland mammal populations. The tendency for faster evolution on islands holds over relatively short time scales—from a few decades up to several thousands of years—but not over larger ones—up to 12 million y. These analyses form the first empirical test of the long held supposition of accelerated evolution among island mammals. Moreover, this result shows that mammal species have the intrinsic capacity to evolve faster when confronted with a rapid change in their environment. This finding is relevant to our understanding of species' responses to isolation and destruction of natural habitats within the current context of rapid climate warming.     

The maximal body mass–area relationship in island mammals

Aim A positive power relationship between maximal body mass and land area has previously been reported of the form M_max ∝ Area^0.5 whilst allometric scaling theory predicts either M_max ∝ Area^1.33 or M_max ∝ Area¹. We provide an analysis of the maximal mass–area relationship for four island systems, to test the hypothesis that community relaxation following isolation converges in each case to a slope of Area^0.5. Location Islands of the Japanese archipelago, the western Mediterranean, the Sea of Cortés and Southeast Asia. Methods We calculated the relationship between island area and the maximal body mass of the largest mammal species on the island using linear regression models with log‐transformed variables, and tested the hypothesis that the slopes were not significantly different from 0.5. Results We found a slope of 0.47 within the Japanese archipelago, 0.42 for western Mediterranean islands, 0.73 for the Sea of Cortés islands and 0.50 for Southeast Asian islands. None of these slopes were significantly different from 0.5. Main conclusions Our results provide further empirical support for previous findings of a general maximal body mass–area relationship of M_max ∝ Area^0.5, but they deviate from theoretical predictions. We hypothesize that this mass–area relationship was the ultimate end point of community relaxation initiated by the isolation of the mammal communities. Maximal body mass on each island today probably reflects the interaction between energetic constraints, home range size and island area.     

Key developmental regulators change during hyperoxia-induced injury and recovery in adult mouse lung

Developmentally important genes have recently been linked to tissue regeneration and epithelial cell repair in neonatal and adult animals in several organs, including liver, skin, prostate, and musculature. We hypothesized that developmentally important genes play roles in lung injury repair in adult mice. Although there is considerable information known about these processes, the specific molecular pathways that mediate injury and regulate tissue repair are not fully elucidated. Using a hyperoxic injury model to study these mechanisms of lung injury and tissue repair, we selected the following genes based upon their known or putative roles in lung development and organogenesis: TTF-1, FGF9, FGF10, BMP4, PDGF-A, VEGF, Ptc, Shh, Sca-1, BCRP, CD45, and Cyclin-D2. Our findings demonstrate that several developmentally important genes (Sca-1, Shh, PDGF-A, VEGF, BCRP, CD45, BMP4, and Cyclin-D2) change during hyperoxic injury and normoxic recovery in mice, suggesting that adult lung may reactivate key developmental regulatory pathways for tissue repair. The mRNA for one gene (TTF-1), unchanged during hyperoxia, was upregulated late in recovery phase. These novel findings provide the basis for testing the efficacy of post-injury lung repair in animals genetically modified to inactivate or express individual molecules.     

Early sequence of events triggered by the interaction of Neisseria meningitidis with endothelial cells

Neisseria meningitidis is a bacterium responsible for severe sepsis and meningitis. Following type IV pilus‐mediated adhesion to endothelial cells, bacteria proliferating on the cellular surface trigger a potent cellular response that enhances the ability of adhering bacteria to resist the mechanical forces generated by the blood flow. This response is characterized by the formation of numerous 100 nm wide membrane protrusions morphologically related to filopodia. Here, a high‐resolution quantitative live‐cell fluorescence microscopy procedure was designed and used to study this process. A farnesylated plasma membrane marker was first detected only a few seconds after bacterial contact, rapidly followed by actin cytoskeleton reorganization and bulk cytoplasm accumulation. The bacterial type IV pili‐associated minor pilin PilV is necessary for the initiation of this cascade. Plasma membrane composition is a key factor as cholesterol depletion with methyl‐β‐cyclodextrin completely blocks the initiation of the cellular response. In contrast membrane deformation does not require the actin cytoskeleton. Strikingly, plasma membrane remodelling undermicrocolonies is also independent of common intracellular signalling pathways as cellular ATP depletion is not inhibitory. This study shows that bacteria‐induced plasma membrane reorganization is a rapid event driven by a direct cross‐talk between type IV pili and the plasma membrane rather than by the activation of an intracellular signalling pathway that would lead to actin remodelling.