Knockdown of flotillin-2 inhibits lung surfactant secretion by alveolar type II cells

Dear Editor,
Lung surfactant is stored in lamellar bodies and exocytosed following fusion of the lamellar bodies with the plasma membrane of alveolar type II （AT2） cells [1]. A number of proteins have been shown to be involved in surfactant secretion including SNAREs, NSF, α-SNAP and annexin A2 [2, 3]. Lipid rafts enriched in SNAREs are crucial for surfactant secretion [4].     

Enhancement of memory function in aged mice by a novel derivative of xanomeline

In age-related cognitive deficits and Alzheimer＇s disease （AD）, one of the most common pathological changes appears to be the loss of cholinergic neurons in the forebrain and the depletion of cortical cholinergic axons [1]. Accordingly, attempts have been made to generate therapies that aim to reverse the cognitive deficits associated with AD and aging by direct stimulation of mAChRs with specific agonists.     

Influence of pigment substitution on the electrochemical properties ofRhodobacter sphaeroides 601 reaction centers

With the help of pigment substitution, self-assembled monolayer film and square wave voltammetry, the influence of pigment substitution on the electrochemical properties ofRhodobacter sphaeroides 601 reaction centers was investigated. Results showed that the charge separation could also be driven by externally electric field, similar to the primary photochemical reaction in purple bacterial reaction center. On the surface of Au electrode, a self-assembled monolayer film (the RC-PDDA-DMSA film) was made up of 2,3-dimercaptosuccinic acid (DMSA), poly-dimethyldiallylammonium chloride (PDDA) and reaction center (RC). When square wave voltammetry was used to study the RC-PDDA-DMSA film, four redox pairs in the photochemical reaction of RC were observed by changing frequency. With nonlinear fitting, the standard potential of P/P⁺ and the corresponding electrode reaction rate constant were determined to be 0.522 V and 13.04 S^-1, respectively. It was found that the redox peak at −0.02 V changed greatly when bacteriopheophytin was substituted by plant pheophytin in the reaction center. Further studies indicated that this change resulted from the decrease in electron transfer rate between Bphe^-/Bphe (Phe^-/Phe) and Q_A ^-/Q_A after pigment substitution. After investigations of spectra and electrochemical properties of different RCs and comparisons of different function groups of pigments, it was indicated that the phytyl tail, similar to other substituted groups of pheophytin, affected the efficiencies of pigment substitution.     

Strain energy function for biological tissues

The purpose of this paper is to investigate a possible form of the elastic energy function for soft tissues, which can reproduce the characteristic feature as observed in experiments. The function is assumed to be the sum of the distortional and the dilatational strain energy. The relations between the axial stress and deformation in uniaxial tension are plotted.     

Phylogeny of the Trichostrongylina (Nematoda) inferred from 28S rDNA sequences

We produced a molecular phylogeny of species within the order Strongylida (bursate nematodes) using the D1 and D2 domains of 28S rDNA, with 23 new sequences for each domain. A first analysis using Caenorhabditis elegans as an outgroup produced a tree with low resolution in which three taxa (Dictyocaulus filaria, Dictyocaulus noerneri, and Metastrongylus pudendotectus) showed highly divergent sequences. In a second analysis, these three species and C. elegans were removed and an Ancylostomatina, Bunostomum trigonocephalum, was chosen (on the basis of previous morphological analyses) as the outgroup for an analysis of the phylogenetic relationships between and within the Strongylina (strongyles) and Trichostrongylina (trichostrongyles). A very robust tree was obtained. The Trichostrongylina were monophyletic, but the Strongylina were paraphyletic, though this requires confirmation. Within the Trichostrongylina, the three superfamilies defined from morphological characters are confirmed, with the Trichostrongyloidea sister group to a clade including the Molineoidea and Heligmosomoidea. Within the Trichostrongyloidea, the Cooperiidae, Trichostrongylidae, and Haemonchidae were polytomous, the Haemonchinae were monophyletic, but the Ostertagiinae were paraphyletic. The sister-group relationships between Molineoidea and Heligmosomoidea were unsuspected from previous morphological analysis. No unequivocal morphological synapomorphy could be found for the grouping Molineoidea + Heligmosomoidea, but none was found which contradicted it.     

Protein nitration in rat lungs during hyperoxia exposure: a possible role of myeloperoxidase

Several studies have suggested that exposure to hyperoxia causes lung injury through increased generation of reactive oxygen and nitrogen species. The present study was aimed to investigate the effects of hyperoxia exposure on protein nitration in lungs. Rats were exposed to hyperoxia (>95%) for 48, 60, and 72 h. Histopathological analysis showed a dramatic change in the severity of lung injury in terms of edema and hemorrhage between 48- and 60-h exposure times. Western blot for nitrotyrosine showed that several proteins with molecular masses of 29-66 kDa were nitrated in hyperoxic lung tissues. Immunohistochemical analyses indicate nitrotyrosine staining of alveolar epithelial and interstitial regions. Furthermore, immunoprecipitation followed by Western blot revealed the nitration of surfactant protein A and t1alpha, proteins specific for alveolar epithelial type II and type I cells, respectively. The increased myeloperoxidase (MPO) activity and total nitrite levels in bronchoalveolar lavage and lung tissue homogenates were observed in hyperoxic lungs. Neutrophils and macrophages isolated from the hyperoxia-exposed rats, when cocultured with a rat lung epithelial L2 cell line, caused a significant protein nitration in L2 cells. Inclusion of nitrite further increased the protein nitration. These studies suggest that protein nitration during hyperoxia may be mediated in part by MPO generated from activated phagocytic cells, and such protein modifications may contribute to hyperoxia-mediated lung injury.     

Algicidal activity and gliding motility of Saprospira sp. SS98-5

A marine bacterium, Saprospira sp. SS98-5, which was isolated from Kagoshima Bay, Japan, was able to kill and lyse the cells of the diatom Chaetoceros ceratosporum. The multicellular filamentous cells of this bacterium captured the diatom cells, formed cell aggregates, and lysed them in an enriched sea water (ESS) liquid medium. Strain SS98-5 also formed plaques on double layer agar plates incorporating diatom cells. The diatom cell walls were partially degraded at the contact sites with the bacteria, the bacteria invaded from there into the diatom cells, and then the diatom cells were completely lysed. The strain possessed gliding motility and grew as spreading colonies on ESS agar plates containing lower concentrations of polypeptone (below 0.1%) while forming nonspreading colonies on ESS agar plates containing 0.5% polypeptone. Electron micrographs of ultrathin sections demonstrated that microtubule-like structures were observable only in gliding motile cells. Both the gliding motility and the microtubule-like structures were diminished by the addition of podophyllotoxin, an inhibitor of microtubule assembly, suggesting that the microtubule-like structures observed in these bacterial cells are related to their gliding motility.     

Dominant cataracts result from incongruous mixing of wild-type lens connexins

Gap junctions are composed of proteins called connexins (Cx) and facilitate both ionic and biochemical modes of intercellular communication. In the lens, Cx46 and Cx50 provide the gap junctional coupling needed for homeostasis and growth. In mice, deletion of Cx46 produced severe cataracts, whereas knockout of Cx50 resulted in significantly reduced lens growth and milder cataracts. Genetic replacement of Cx50 with Cx46 by knockin rescued clarity but not growth. By mating knockin and knockout mice, we show that heterozygous replacement of Cx50 with Cx46 rescued growth but produced dominant cataracts that resulted from disruption of lens fiber morphology and crystallin precipitation. Impedance measurements revealed normal levels of ionic gap junctional coupling, whereas the passage of fluorescent dyes that mimic biochemical coupling was altered in heterozygous knockin lenses. In addition, double heterozygous knockout lenses retained normal growth and clarity, whereas knockover lenses, where native Cx46 was deleted and homozygously knocked into the Cx50 locus, displayed significantly deficient growth but maintained clarity. Together, these findings suggest that unique biochemical modes of gap junctional communication influence lens clarity and lens growth, and this biochemical coupling is modulated by the connexin composition of the gap junction channels.     

Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation

Cell-extracellular matrix adhesion is an important determinant of cell morphology. We show here that migfilin, a LIM-containing protein, localizes to cell-matrix adhesions, associates with actin filaments, and is essential for cell shape modulation. Migfilin interacts with the cell-matrix adhesion protein Mig-2 (mitogen inducible gene-2), a mammalian homolog of UNC-112, and the actin binding protein filamin through its C- and N-terminal domains, respectively. Loss of Mig-2 or migfilin impairs cell shape modulation. Mig-2 recruits migfilin to cell-matrix adhesions, while the interaction with filamin mediates the association of migfilin with actin filaments. Migfilin therefore functions as an important scaffold at cell-matrix adhesions. Together, Mig-2, migfilin and filamin define a connection between cell matrix adhesions and the actin cytoskeleton and participate in the orchestration of actin assembly and cell shape modulation.