Mesenchymal stem cells within tumour stroma promote breast cancer metastasis

Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells.     

Generation of functional multipotent adult stem cells from GPR125+ germline progenitors

Adult mammalian testis is a source of pluripotent stem cells. However, the lack of specific surface markers has hampered identification and tracking of the unrecognized subset of germ cells that gives rise to multipotent cells. Although embryonic-like cells can be derived from adult testis cultures after only several weeks in vitro, it is not known whether adult self-renewing spermatogonia in long-term culture can generate such stem cells as well. Here, we show that highly proliferative adult spermatogonial progenitor cells (SPCs) can be efficiently obtained by cultivation on mitotically inactivated testicular feeders containing CD34+ stromal cells. SPCs exhibit testicular repopulating activity in vivo and maintain the ability in long-term culture to give rise to multipotent adult spermatogonial-derived stem cells (MASCs). Furthermore, both SPCs and MASCs express GPR125, an orphan adhesion-type G-protein-coupled receptor. In knock-in mice bearing a GPR125-beta-galactosidase (LacZ) fusion protein under control of the native Gpr125 promoter (GPR125-LacZ), expression in the testis was detected exclusively in spermatogonia and not in differentiated germ cells. Primary GPR125-LacZ SPC lines retained GPR125 expression, underwent clonal expansion, maintained the phenotype of germline stem cells, and reconstituted spermatogenesis in busulphan-treated mice. Long-term cultures of GPR125+ SPCs (GSPCs) also converted into GPR125+ MASC colonies. GPR125+ MASCs generated derivatives of the three germ layers and contributed to chimaeric embryos, with concomitant downregulation of GPR125 during differentiation into GPR125- cells. MASCs also differentiated into contractile cardiac tissue in vitro and formed functional blood vessels in vivo. Molecular bookmarking by GPR125 in the adult mouse and, ultimately, in the human testis could enrich for a population of SPCs for derivation of GPR125+ MASCs, which may be employed for genetic manipulation, tissue regeneration and revascularization of ischaemic organs.     

Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding

The mammalian hair follicle is a complex 'mini-organ' thought to form only during development; loss of an adult follicle is considered permanent. However, the possibility that hair follicles develop de novo following wounding was raised in studies on rabbits, mice and even humans fifty years ago. Subsequently, these observations were generally discounted because definitive evidence for follicular neogenesis was not presented. Here we show that, after wounding, hair follicles form de novo in genetically normal adult mice. The regenerated hair follicles establish a stem cell population, express known molecular markers of follicle differentiation, produce a hair shaft and progress through all stages of the hair follicle cycle. Lineage analysis demonstrated that the nascent follicles arise from epithelial cells outside of the hair follicle stem cell niche, suggesting that epidermal cells in the wound assume a hair follicle stem cell phenotype. Inhibition of Wnt signalling after re-epithelialization completely abrogates this wounding-induced folliculogenesis, whereas overexpression of Wnt ligand in the epidermis increases the number of regenerated hair follicles. These remarkable regenerative capabilities of the adult support the notion that wounding induces an embryonic phenotype in skin, and that this provides a window for manipulation of hair follicle neogenesis by Wnt proteins. These findings suggest treatments for wounds, hair loss and other degenerative skin disorders.     

Genome-wide expression dynamics of a marine virus and host reveal features of co-evolution

Interactions between bacterial hosts and their viruses (phages) lead to reciprocal genome evolution through a dynamic co-evolutionary process. Phage-mediated transfer of host genes--often located in genome islands--has had a major impact on microbial evolution. Furthermore, phage genomes have clearly been shaped by the acquisition of genes from their hosts. Here we investigate whole-genome expression of a host and phage, the marine cyanobacterium Prochlorococcus MED4 and the T7-like cyanophage P-SSP7, during lytic infection, to gain insight into these co-evolutionary processes. Although most of the phage genome was linearly transcribed over the course of infection, four phage-encoded bacterial metabolism genes formed part of the same expression cluster, even though they are physically separated on the genome. These genes--encoding photosystem II D1 (psbA), high-light inducible protein (hli), transaldolase (talC) and ribonucleotide reductase (nrd)--are transcribed together with phage DNA replication genes and seem to make up a functional unit involved in energy and deoxynucleotide production for phage replication in resource-poor oceans. Also unique to this system was the upregulation of numerous genes in the host during infection. These may be host stress response genes and/or genes induced by the phage. Many of these host genes are located in genome islands and have homologues in cyanophage genomes. We hypothesize that phage have evolved to use upregulated host genes, leading to their stable incorporation into phage genomes and their subsequent transfer back to hosts in genome islands. Thus activation of host genes during infection may be directing the co-evolution of gene content in both host and phage genomes.     

Control of vehicle platoons for highway safety and efficient utility: Consensus with communications and vehicle dynamics

Platoon formation of highway vehicles is a critical foundation for autonomous or semiautonomous vehicle control for enhanced safety,improved highway utility,increased fuel economy,and reduced emission toward intelligent transportation systems.Platoon control encounters great challenges from vehicle control,communications,team coordination,and uncertainties.This paper introduces a new method for coordinated control of platoons by using integrated network consensus decisions and vehicle control.To achieve suitable coordination of the team vehicles based on terrain and environmental conditions,the emerging technology of network consensus control is modified to a weighted and constrained consensus-seeking framework.Algorithms are introduced and their convergence properties are established.The methodology employs neighborhood information through on-board sensors and V2 V or V2 I communications,but achieves global coordination of the entire platoon.The ability of the methods in terms of robustness,disturbance rejection,noise attenuation,and cyber-physical interaction is analyzed and demonstrated with simulated case studies.     

Transplanted bone marrow regenerates liver by cell fusion

Results from several experimental systems suggest that cells from one tissue type can form other tissue types after transplantation. This could be due to the presence of multipotential or several types of adult stem cells in donor tissues, or alternatively, to fusion of donor and recipient cells. In a model of tyrosinaemia type I, mice with mutations in the fumarylacetoacetate hydrolase gene (Fah-/-) regain normal liver function after transplantation of Fah+/+ bone marrow cells, and form regenerating liver nodules with normal histology that express Fah. Here we show that these hepatic nodules contain more mutant than wild-type Fah alleles, and that their hepatocytes express both donor and host genes, consistent with polyploid genome formation by fusion of host and donor cells. Using bone marrow cells marked with integrated foamy virus vectors that express green fluorescent protein, we identify common proviral junctions in hepatic nodules and haematopoietic cells. We also show that the haematopoietic donor genome adopts a more hepatocyte-specific expression profile after cell fusion, as the wild-type Fah gene was activated and the pan-haematopoietic CD45 marker was no longer expressed.     

Microtopography of microbiotic crusts on the Colorado Plateau, and distribution of component organisms

We analyzed the microtopography of microbiotic soil crusts at 3 sites on the Colorado Plateau of southern Utah and investigated distributions of cyanobacteria and several lichens in distinctive microhabitats created by this topography. At all 3 sites the long axes of linear soil mounds were oriented nonrandomly in a NNW—SSE direction. The conspicuous and consistent orientation of soil mounds may result from a combination of physical and biotic processes. Subtle differences across sites in mound orientation and organismal distribution suggest that these variables may be useful in comparing disturbance histories of crusts retrospectively. Differences in colonization frequencies, abundances, and distributions of microorganisms comprising the crusts, as a function of mound aspect or exposure, suggest that these organisms are associated with particular aspects due to distinctive and favorable microhabitats on these exposures. Polysaccharide sheath material, deposited by cyanobacteria, and associated filaments occurred in greater quantities on ENE than WSW mound exposures, and cover by Collema spp. lichens exhibited the same pattern. Colonization of mounds by common lichen species occurred significantly more frequently on ENE than WSW mound aspects at 2 of 3 sites. In contrast, the 3 most common lichen species, aside from Collema spp., did not exhibit a tendency for greater cover on ENE than WSW mound aspects. Physiological differences between gelatinous cyanolichens and green-algal lichens may explain the different distributional patterns of Collema spp. and the 3 other lichens.     

烯-二炔”模型化合物前体：6-硫杂-13-氧杂双环［9．3．0］-3，8-十四二炔的合成

以顺 1,2 ,3,6 四氢邻苯二甲酸酐为原料 ,经还原 ,羟基保护 ,双键臭氧化开环 ,Wittig反应 ,双炔化 ,酯化 ,二醇化 ,二磺酸酯化 ,硫化 ,醇缩合共十步 ,合成了“烯 二炔”前体物 :6 硫杂 13 氧杂双环 [9.3.0 ] 3,8 十四二炔 .该合成法收率较高 ,反应条件温和 ,新化合物 ( 8) ,( 10 ) ,( 11)经元素分析 ,核磁 ,红外 ,质谱确证结构 .