p53 mutant mice that display early ageing-associated phenotypes.

The p53 tumour suppressor is activated by numerous stressors to induce apoptosis, cell cycle arrest, or senescence. To study the biological effects of altered p53 function, we generated mice with a deletion mutation in the first six exons of the p53 gene that express a truncated RNA capable of encoding a carboxy-terminal p53 fragment. This mutation confers phenotypes consistent with activated p53 rather than inactivated p53. Mutant (p53+/m) mice exhibit enhanced resistance to spontaneous tumours compared with wild-type (p53+/+) littermates. As p53+/m mice age, they display an early onset of phenotypes associated with ageing. These include reduced longevity, osteoporosis, generalized organ atrophy and a diminished stress tolerance. A second line of transgenic mice containing a temperature-sensitive mutant allele of p53 also exhibits early ageing phenotypes. These data suggest that p53 has a role in regulating organismal ageing.     

厌气反应器对基质扰乱的响应

5套 37℃的扰乱试验实施在 3台厌气完全混合反应器中。三反应器分别处理着以丙酸、丁酸和混合脂肪酸为基质的废水。扰乱由脉冲添加丙酸、丁酸或甲酸来建立。结果表示 ,扰乱立即导致了相应的酸和氢分压(pH2 )的浓度积累。但所有反应器能完全地恢复在 2 0 0h之内。混合液相中丙酸和丁酸的积累没有导致pH的重大变化。但是 ,PH2 的增加限制了丙酸和丁酸的转换 ;各自的阈值分别为 2 1× 10 - 4及 1 1× 10 - 3atm。异丁酸和二高分子羟基酸 ,valerate和caproate ,被检出存在于一些被扰乱的反应器流出水中。对于丁酸异构化pH2 的作用是非决定性的。实验数据的热力学分析表示 ,valerate和caproate的形成或归结于pH2 的增加或独立于pH2 的增加。在后者 ,形成直接地归结于混合液相中丙酸或丁酸的浓度增加。     

Cloning and sequence analysis of cDNA for bovine carboxypeptidase E

Carboxypeptidase E (enkephalin convertase) was first identified as the carboxypeptidase B-like enzyme involved in the biosynthesis of enkephalin in bovine adrenal chromaffin granules. A similar enzyme is present in many brain regions and in purified secretory granules from rat pituitary and rat insulinoma. Within the secretory granules, carboxypeptidase E (CPE) activity is found in both a soluble and a membrane-bound form, which differ slightly in relative molecular mass (Mr). Here, to investigate whether the CPE activities in the various tissues are produced from a single gene, purified CPE was partially sequenced and oligonucleotide probes were used to isolate a clone encoding CPE from a bovine pituitary complementary DNA library. This cDNA hybridizes to bovine pituitary poly(A)+ RNAs of approximately 3.3, 2.6 and 2.1 kilobases (kb), with the 3.3-kb messenger RNA the predominant species. The predicted amino-acid sequence of the cDNA clone contains the partially determined sequences of CPE, several pairs of basic amino acids and displays some homology with both carboxypeptidases A and B. Restriction analysis of bovine genomic DNA suggests only one gene for CPE. This is consistent with a broad role for CPE in the biosynthesis of many neuropeptides.     

影响聚丙烯酰胺在土壤和水分管理应用的因素

水溶性阴离子聚丙烯酰胺(PAMs)。因其影响土壤的分散、结絮和团聚作用，稳定土壤的结构争提高土壤的渗流，使得土壤地表水的径流、土壤侵蚀和板结程度降低到最小。已被应用于不同的农业目标来有效地控制土壤侵蚀、保护地下水水质和显著地降低动物废弃水中的细菌和养分含量。对影响PAM在土壤和水分管理应用的因素，从土壤和水特性包括土壤质地、溶解盐的浓度、有机质含量对PAM吸附的影响，PAM分子量及其电荷在土壤渗透作用中的作用等两方面进行了评述，介绍了PAM在土壤和水中降解与环境安全问题和今后研究的某些方向。参36。     

De novo hem- and lymphangiogenesis by endothelial progenitor and mesenchymal stem cells in immunocompetent mice

Cellular pro-angiogenic therapies may be applicable for the treatment of peripheral vascular diseases. Interactions between mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) may provide such a treatment option. With the exception of some studies in man, experiments have only been performed in immunodeficient mice and rats. We studied an immunocompetent syngeneic mouse model. We isolated MSCs from bone marrow and EPCs from the lung of adult C57/Bl.6 mice and co-injected them in Matrigel subcutaneously in adult C57/Bl.6 mice. We demonstrate development of both blood vessels and lymphatics. Grafted EPCs integrated into the lining of the two vessel types, whereas MSCs usually did not incorporate into the vessel wall. Injections of each separate cell type did not, or hardly, reveal de novo angiogenesis. The release of VEGF-A by MSCs has been shown before, but its inhibitors, e.g., soluble VEGF receptors, have not been studied. We performed qualitative and quantitative studies of the proteins released by EPCs, MSCs, and cocultures of the cells. Despite the secretion of VEGF inhibitors (sVEGFR-1, sVEGFR-2) by EPCs, VEGF-A was secreted by MSCs at bioavailable amounts (350 pg/ml). We confirm the secretion of PlGF, FGF-1, MCP-1, and PDGFs by EPCs/MSCs and suggest functions for VEGF-B, amphiregulin, fractalkine, CXCL10, and CXCL16 during MSC-induced hem- and lymphangiogenesis. We assume that lymphangiogenesis is induced indirectly by growth factors from immigrating leukocytes, which we found in close association with the lymphatic networks. Inflammatory responses to the cellular markers GFP and cell-tracker red (CMPTX) used for tracing of EPCs or MSCs were not observed. Our studies demonstrate the feasibility of pro-angiogenic/lymphangiogenic therapies in immunocompetent animals and indicate new MSC/EPC-derived angiogenic factors.     

Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression

Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency induces iron overload, whereas hepcidin excess induces anemia. Mutations in the gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload and correlate with low hepcidin levels, suggesting that hemojuvelin positively regulates hepcidin expression. Hemojuvelin is a member of the repulsive guidance molecule (RGM) family, which also includes the bone morphogenetic protein (BMP) coreceptors RGMA and DRAGON (RGMB). Here, we report that hemojuvelin is a BMP coreceptor and that hemojuvelin mutants associated with hemochromatosis have impaired BMP signaling ability. Furthermore, BMP upregulates hepatocyte hepcidin expression, a process enhanced by hemojuvelin and blunted in Hfe2-/- hepatocytes. Our data suggest a mechanism by which HFE2 mutations cause hemochromatosis: hemojuvelin dysfunction decreases BMP signaling, thereby lowering hepcidin expression.     

Bi-orientation of achiasmatic chromosomes in meiosis I oocytes contributes to aneuploidy in mice

The spindle assembly checkpoint guards against chromosomal missegregation but does not induce arrest in oocytes that contain a few achiasmatic chromosomes (univalents). We followed the fate of univalents in oocytes during the first meiotic division, and although these preserved a meiotic kinetochore structure, they were also bi-oriented in a mitotic manner. The hybrid chromosomal configuration attained by univalents allows them to evade the spindle assembly checkpoint and contribute to aneuploidy in oocytes.