Control of type II transforming growth factor-beta receptor expression by integrin ligation

Ectopic expression of the alpha5 integrin subunit in cancer cells with little or no endogenous expression of this integrin often results in reduced proliferation as well as reduced malignancy. We now show that inhibition resulting from ectopic expression of alpha5 integrin is due to induction of autocrine negative transforming growth factor-beta (TGF-beta) activity. MCF-7 breast cancer cells do not express either alpha5 integrin or type II TGF-beta receptor and hence are unable to generate TGF-beta signal transduction. Ectopic expression of alpha5integrin expression enhanced cell adhesion to fibronectin, reduced proliferation, and increased the expression of type II TGF-beta receptor mRNA and cell surface protein. Receptor expression was increased to a higher level in alpha5 transfectants by growth on fibronectin-coated plates. Induction of type II TGF-beta receptor expression also resulted in the generation of autocrine negative TGF-beta activity because colony formation was increased after TGF-beta neutralizing antibody treatment. Transient transfection with a TGF-beta promoter response element in tandem with a luciferase cDNA into cells stably transfected with alpha5 integrin resulted in basal promoter activities 5-10-fold higher than those of control cells. Moreover, when alpha5 transfectants were treated with a neutralizing antibody to either TGF-beta or integrin alpha5, this increased basal promoter activity was blocked. Autocrine TGF-beta activity also induced 3-fold higher endogenous fibronectin expression in alpha5 transfectants relative to that of control cells. Re-expression of type II receptor by alpha5 transfection also restored the ability of the cells to respond to exogenous TGF-beta and led to reduced tumor growth in athymic nude mice. Taken together, these results show for the first time that TGF-beta type II receptor expression can be controlled by alpha5beta1 ligation and integrin signal transduction. Moreover, TGF-beta and integrin signal transduction appear to cooperate in their tumor-suppressive functions.     

Protocadherin 2C: a new member of the protocadherin 2 subfamily expressed in a redundant manner with OL-protocadherin in the developing brain.

Using cDNA of human protocadherin 2A (pc2A; originally known as protocadherin 2) as a probe, we cloned a new member of the protocadherin 2 subfamily from mouse brain cDNA libraries and named it protocadherin 2C (pc2C). It was similar to pc2A throughout its entire coding region, and its C-terminal region was highly conserved. The locus of the pc2C gene was on the mouse chromosome 18C where the pc2A gene is located, suggesting that genes of the pc2 subfamily form a gene cluster. The expression of pc2C was restricted to the nervous system, and the expression started in the embryonic stage and increased up to the adult stage. The expression pattern was quite similar to that of OL-protocadherin, a distinct class of protocadherin, although the timing and relative strength of expression were different. These results suggest that pc2C may be involved in neural development along with other classes of protocadherins.     

Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II.

Caspases are cysteine proteases that mediate programmed cell death in phylogenetically diverse multicellular organisms. We report here two kindreds with autoimmune lymphoproliferative syndrome (ALPS) type II, characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects, that harbor independent missense mutations in Caspase 10. These encode amino acid substitutions that decrease caspase activity and interfere with death receptor-induced apoptosis, particularly that stimulated by Fas ligand and TRAIL. These results provide evidence that inherited nonlethal caspase abnormalities cause pleiotropic apoptosis defects underlying autoimmunity in ALPS type II.     

贵阳孟关早三叠世安顺组的两个新遗迹属

记述２个新遗迹属──Ｂｉｃｏｎｃａｖｉｃｈｎｕｓ和Ｆａｓｃｉａｒｉｃｈｎｕｓ，并讨论了它们的形成方式和形成环境。化石产于贵阳市南约２０ｋｍ的孟关附近的下三叠统安顺组上部。     

Synthesis and characterization of three group 10 complexes containing nido-carborane diphosphine: [MCl(PPh3){7,8-(PPh2)2-7,8-C2B9H10}] (M = Ni, Pd, Pt)

Three group 10 complexes containing nido-carborane diphosphine, [NiCl(PPh₃){7,8-(PPh₂)₂-7,8-C₂B₉H₁₀}] (1), [PdCl(PPh₃){7,8-(PPh₂)₂-7,8-C₂B₉H₁₀}] · 1.25CH₂Cl₂ (2) and [PtCl(PPh₃){7,8-(PPh₂)₂-7,8-C₂B₉H₁₀}] · 2.5CH₂Cl₂ (3) have been synthesized by the reactions of [M(PPh₃)₂Cl₂] (M = Ni, Pd, Pt) with closo carborane diphosphine 1,2-(PPh₂)₂-1,2-C₂B₁₀H₁₀ in ethanol. For complex 3, it could also be obtained under solvothermal condition. All three complexes were characterized by elemental analysis, FT-IR, ¹H and ¹³C NMR spectroscopy and X-ray structure determination. Single crystal structures show that their structures are similar to each other. In each complex, the nido [7,8-(PPh₂)₂-7,8-C₂B₉H₁₀]⁻, which resulted from the degradation of the initial closo ligand 1,2-(PPh₂)₂-1,2-C₂B₁₀H₁₀ during the reaction process, was coordinated bidentately through the P atoms to M(II) ion, and this resulted in a stable five-membered chelating ring between the bis-diphosphine ligand and the metal. The coordination mode of the metal can be described as a slightly distorted square-planar, in which the remaining two positions were occupied by one Cl⁻ and one PPh₃ group.     

CD4 + CD25<Superscript>high</Superscript> Regulatory T Cell Numbers and FOXP3 mRNA Expression in Patients with Advanced Esophageal Cancer Before and After Chemotherapy

We evaluated the changes in CD4 + CD25^high regulatory T (Treg) cells and FOXP3 mRNA expression in patients with advanced esophageal cancer as well as its clinical significance. For this purpose, the frequencies of peripheral blood Treg cells in 68 patients with advanced esophageal cancer and 40 healthy controls were determined by flow cytometry, and FOXP3 mRNA expression in Treg cells of 40 patients was determined by RT–PCR. The data show that Treg cell numbers were significantly higher (P < 0.01) in esophageal cancer patients (1.82 ± 0.54% of CD4 + T cells) as compared with healthy controls (1.52 ± 0.70% of CD4⁺ T cells). Treg cell numbers in the patients were significantly higher (P < 0.05) before chemotherapy (1.82 ± 0.54% of CD4 + T cells) than after chemotherapy (1.66 ± 0.58% of CD4 + T cells). Expression of the FOXP3 mRNA in the patients was significantly lower (P < 0.05) after chemotherapy (0.266 ± 0.028% of CD4 + T cells) than before chemotherapy (0.318 ± 0.027% of CD4 + T cells). It was, therefore, concluded that Treg cell numbers as well as FOXP3 mRNA expression in advanced esophageal cancer patients were significantly decreased after chemotherapy. Notably, FOXP3 gene may thus be involved in regulating the numbers and function of Treg cells in advanced esophageal cancer patients receiving chemotherapy.     

Transition of basic protein during spermatogenesis of <Emphasis Type="Italic">Fenneropenaeus chinensis</Emphasis> (Osbeck, 1765)

According to the ultrastructural characteristic observation of the developing male germ cells, spermatogenesis of the crustacean shrimp, Fenneropenaeus chinensis, is classified into spermatogonia, primary spermatocytes, secondary spermatocyte, four stages of spermatids, and mature sperm. The basic protein transition during its spermatogenesis is studied by transmission electron microscopy of ammoniacal silver reaction and immunoelectron microscopical distribution of acetylated histone H4. The results show that basic protein synthesized in cytoplasm of spermatogonia is transferred into the nucleus with deposition on new duplicated DNA. In the spermatocyte stage, some nuclear basic protein combined with RNP is transferred into the cytoplasm and is involved in forming the cytoplasmic vesicle clumps. In the early spermatid, most of the basic protein synthesized in the new spermatid cytoplasm is transferred into the nucleus, and the chromatin condensed gradually, and the rest is shifted into the pre-acrosomal vacuole. In the middle spermatid, the nuclear basic protein linked with DNA is acetylated and transferred into the proacrosomal vacuole and assembled into the acrosomal blastema. At the late spermatid, almost all of the basic protein in the nucleus has been removed into the acrosome. During the stage from late spermatid to mature sperm, some de novo basic proteins synthesized in the cytoplasm belt transfer into the nucleus without a membrane and almost all deposit in the periphery to form a supercoating. The remnant histone H4 accompanied by chromatin fibers is acetylated in the center of the nucleus, leading to relaxed DNA and activated genes making the nucleus non-condensed.