p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation

Stem cell function is central for the maintenance of normal tissue homeostasis. Here we show that deletion of p38alpha mitogen-activated protein (MAP) kinase in adult mice results in increased proliferation and defective differentiation of lung stem and progenitor cells both in vivo and in vitro. We found that p38alpha positively regulates factors such as CCAAT/enhancer-binding protein that are required for lung cell differentiation. In addition, p38alpha controls self-renewal of the lung stem and progenitor cell population by inhibiting proliferation-inducing signals, most notably epidermal growth factor receptor. As a consequence, the inactivation of p38alpha leads to an immature and hyperproliferative lung epithelium that is highly sensitized to K-Ras(G12V)-induced tumorigenesis. Our results indicate that by coordinating proliferation and differentiation signals in lung stem and progenitor cells, p38alpha has a key role in the regulation of lung cell renewal and tumorigenesis.     

The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome

Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and Meckel (MKS) syndrome belong to the group of developmental autosomal recessive disorders that are associated with primary cilium dysfunction. Using SNP mapping, we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm) recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes with the protein products of both NPHP6 and NPHP4, known genes associated with MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In addition, the RPGRIP1L missense mutations found in CORS individuals diminishes the interaction between RPGRIP1L and nephrocystin-4. Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder.     

Proteorhodopsin phototrophy in the ocean.

Proteorhodopsin, a retinal-containing integral membrane protein that functions as a light-driven proton pump, was discovered in the genome of an uncultivated marine bacterium; however, the prevalence, expression and genetic variability of this protein in native marine microbial populations remain unknown. Here we report that photoactive proteorhodopsin is present in oceanic surface waters. We also provide evidence of an extensive family of globally distributed proteorhodopsin variants. The protein pigments comprising this rhodopsin family seem to be spectrally tuned to different habitats--absorbing light at different wavelengths in accordance with light available in the environment. Together, our data suggest that proteorhodopsin-based phototrophy is a globally significant oceanic microbial process.     

Trace metals especially Fe+++ as dietary factors for leafhoppers

Summary Some trace metals are required for development and reproduction, and therefore for continuous rearing of the aster leafhopper,Macrosteles fascifrons, on a holidic diet. Requirement for Fe⁺⁺⁺ becomes apparent immediately in the 1st generation; for Cu⁺⁺ and Zn⁺⁺, in the 3rd. The leafhopper has grown normally and continuously for 3 generations in the absence of manganese.We acknowledge the Minnesota Agricultural Experiment Station and the National Institute of Allergy and Infectious Diseases, USA, for financial supports.     

Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism

Many studies have supported a genetic etiology for autism. Here we report mutations in two X-linked genes encoding neuroligins NLGN3 and NLGN4 in siblings with autism-spectrum disorders. These mutations affect cell-adhesion molecules localized at the synapse and suggest that a defect of synaptogenesis may predispose to autism.     

Chromatographic evidence for murein from the bacteroid symbiotes ofPeriplaneta americana (L)

Zusammenfassung Papierchromatographisch wurde Murein in symbiontischen Bakteroiden derPeriplaneta americana nachgewiesen. Die Murein-Komponente Glukosamin und der Murein-Anzeiger Muramic-Säure wurden mittels Bakteroid-Hydrolysaten identifiziert. Das Vorhandensein von --Diaminopimelic-Säure jedoch konnte nicht einwandfrei festgestellt werden.

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This is paper No. 6175, Scientific Journal Series, Minnesota Agricultural Experiment Station, St. Paul (Minnesota, USA). The work was supported by U.S. Public Health Service Research Grant No. AI 00961, from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.     

Nuclear localization of aldosterone in rat brain cells assessed by autoradiography

Summary Autoradiographic studies with³H aldosterone demonstrate nuclear concentration of hormone in neurons of the hippocampus, septum, allocortical regionss and brain stem reticular formation and motor nuclei of cranial nerves and in the meninges. The results suggest that mineralocorticoids have wide ranging effects on different parts of the central nervous system.This work was supported by the Medical Research Council of Canada and by PHS grant NS09914. We thank Ms Brenda McClain for technical assistance.     

Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis

Intestinal homeostasis is critical for efficient energy extraction from food and protection from pathogens. Its disruption can lead to an array of severe illnesses with major impacts on public health, such as inflammatory bowel disease characterized by self-destructive intestinal immunity. However, the mechanisms regulating the equilibrium between the large bacterial flora and the immune system remain unclear. Intestinal lymphoid tissues generate flora-reactive IgA-producing B cells, and include Peyer's patches and mesenteric lymph nodes, as well as numerous isolated lymphoid follicles (ILFs). Here we show that peptidoglycan from Gram-negative bacteria is necessary and sufficient to induce the genesis of ILFs in mice through recognition by the NOD1 (nucleotide-binding oligomerization domain containing 1) innate receptor in epithelial cells, and beta-defensin 3- and CCL20-mediated signalling through the chemokine receptor CCR6. Maturation of ILFs into large B-cell clusters requires subsequent detection of bacteria by toll-like receptors. In the absence of ILFs, the composition of the intestinal bacterial community is profoundly altered. Our results demonstrate that intestinal bacterial commensals and the immune system communicate through an innate detection system to generate adaptive lymphoid tissues and maintain intestinal homeostasis.     

采用应变梯度硬化模型预测黄铜薄板微弯曲弯矩

通过黄铜板料微弯曲实验,发现其弯曲弯矩存在明显的尺寸效应现象,随板料厚度的减小,弯曲弯矩增大.采用经典塑性理论和不同的应变梯度理论对微弯曲弯矩进行了预测,对比分析结果表明：修正的Nix Gao模型的预测结果更接近于实验结果,并且得出了合理的内禀尺寸表达式;该内禀尺寸与材料的剪切模量、初始屈服极限、柏氏矢量和板料厚度方向上的孪晶数有关.