Hemoglobin causes both endothelium-dependent and endothelium-independent contraction of the pig coronary arteries, independently of an inhibition of EDRF effects

Hemoglobin is widely used as an inhibitor of EDRF effects. Hemoglobin contracts pig coronary arteries in vitro. However, during this contraction, effects of substance P and bradykinin which act via the EDRF are not inhibited. This means that the hemoglobin contraction is not caused by inhibition of the EDRF. This contraction is caused by a substance released from the endothelium, and by eicosano?ds released from the smooth muscles.     

The melanocyte differentiation program predisposes to metastasis after neoplastic transformation

The aggressive clinical behavior of melanoma suggests that the developmental origins of melanocytes in the neural crest might be relevant to their metastatic propensity. Here we show that primary human melanocytes, transformed using a specific set of introduced genes, form melanomas that frequently metastasize to multiple secondary sites, whereas human fibroblasts and epithelial cells transformed using an identical set of genes generate primary tumors that rarely do so. Notably, these melanomas have a metastasis spectrum similar to that observed in humans with melanoma. These observations indicate that part of the metastatic proclivity of melanoma is attributable to lineage-specific factors expressed in melanocytes and not in other cell types analyzed. Analysis of microarray data from human nevi shows that the expression pattern of Slug, a master regulator of neural crest cell specification and migration, correlates with those of other genes that are important for neural crest cell migrations during development. Moreover, Slug is required for the metastasis of the transformed melanoma cells. These findings indicate that melanocyte-specific factors present before neoplastic transformation can have a pivotal role in governing melanoma progression.     

热输入对深海X70粗晶区组织和韧性的影响

为解决深海X70管线钢在实际焊接中粗晶区(CGHAZ)的脆化问题,在不同热循环工艺下对X70管线钢进行了热模拟研究。采用Gleeble-3800热模拟机模拟X70管线钢CGHAZ,研究CGHAZ在10～60 kJ/cm不同热输入(HI)条件下组织和韧性的变化规律,并通过光学显微镜(OM)、扫描电镜(SEM)和夏比冲击试验等手段表征CGHAZ的组织和韧性。结果表明,不同热输入下试验钢的组织主要由粒状贝氏体(GB)、贝氏体铁素体(BF)和马-奥组元(M-A组元)组成;当HI不断增大时,BF比例减少,GB比例增加,M-A组元粗化,冲击吸收能先升高再降低;当HI为20 kJ/cm时,BF和GB可获得优异组合,断口为韧性断裂,冲击吸收能达到173.8 J;当HI大于20 kJ/cm时,断口解离断裂,冲击吸收能下降明显,最低为18.8 J。因此,较低的热输入可提高CGHAZ的韧性,使X70管线钢具有高强度、高韧性和良好的焊接性。研究结果可为优化焊接工艺提供理论依据。     

临近空间等离子体鞘套对太赫兹波传播特性分析

针对高超声速飞行器在临近空间巡航时出现的通信"黑障"问题,根据RAM C提供的飞行试验数据,建立一维等离子体鞘套模型,通过数值计算分析了等离子体与太赫兹波的相互作用机理,并从等离子体厚度、等离子体电子密度、等离子体碰撞频率和太赫兹波入射角等条件得到了太赫兹波在等离子体鞘套中的传输特性曲线。仿真结果表明:把太赫兹波段作为临近空间平台通信,有利于解决"黑障"问题,其中在大气窗口0.22THz处的衰减均在30dB以下。此论证结果可为临近空间平台设计的高超声速飞行器选用通信频段时提供参考。     

Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype

Tetraodon nigroviridis is a freshwater puffer fish with the smallest known vertebrate genome. Here, we report a draft genome sequence with long-range linkage and substantial anchoring to the 21 Tetraodon chromosomes. Genome analysis provides a greatly improved fish gene catalogue, including identifying key genes previously thought to be absent in fish. Comparison with other vertebrates and a urochordate indicates that fish proteins have diverged markedly faster than their mammalian homologues. Comparison with the human genome suggests approximately 900 previously unannotated human genes. Analysis of the Tetraodon and human genomes shows that whole-genome duplication occurred in the teleost fish lineage, subsequent to its divergence from mammals. The analysis also makes it possible to infer the basic structure of the ancestral bony vertebrate genome, which was composed of 12 chromosomes, and to reconstruct much of the evolutionary history of ancient and recent chromosome rearrangements leading to the modern human karyotype.     

Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor.

A critical point during mammalian pregnancy is the implantation of the blastocyst when the embryo attaches to the wall of the uterus. The autonomously developing preimplantation embryo then becomes dependent on the maternal environment for its continued development. Little is known about the regulation of implantation, except that a complex interaction between peptide and steroid hormones synchronizes the preparation of the uterus for implantation with the development of the embryo. Whether the implantation event is under maternal or embryonic control is also unclear (reviewed in refs 1, 2). We have previously shown that a cytokine, leukaemia inhibitory factor (LIF), is expressed in the uterine endometrial glands specifically on the fourth day of pregnancy. This burst of expression is under maternal control and always precedes implantation of the blastocyst. Here we report that transient expression of LIF in mice is essential for implantation. Females lacking a functional LIF gene are fertile, but their blastocysts fail to implant and do not develop. The blastocysts, however, are viable and, when transferred to wild-type pseudopregnant recipients, they can implant and develop to term.     

Initial genome sequencing and analysis of multiple myeloma

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.     

A new member of the immunoglobulin superfamily--CTLA-4

The immunoglobulin superfamily is a group of proteins, each made of one or several domains sharing key structural features with either the variable (V) or the constant (C) immunoglobulin domains. It includes such functionally important members as the immunoglobulins themselves, major histocompatibility complex (MHC) class I and class II and T-cell receptor (TCR) molecules. Several members of this superfamily are expressed on lymphocytes where they are membrane-bound and capable of interactions with other members of the family, thus taking part in cell-cell recognition. In screening mouse cytolytic-T-cell-derived cDNA libraries, we came across cDNA clones defining a sequence, CTLA-4, which could encode a 223-amino-acid protein clearly belonging to the immunoglobulin superfamily. It consists of one V-like domain flanked by two hydrophobic regions, one of which has a structure suggestive of membrane anchoring. CTLA-4 is mainly expressed in activated lymphocytes and is coinduced with T-cell-mediated cytotoxicity in inducible models of this process. The mouse ctla-4 gene maps to band C of chromosome 1.