Intense Flowing Hollow Cathode Lamp

An inexpensive, simple, and versatile hollow cathode lamp has been developed which produces intense ion resonance radiation of about 1 mW into 4π/25 sr. The lamp employs flowing helium gas to sustain the discharge. The construction permits a variety of cathode seed materials to be easily interchanged. The same lamp has been used as a source of ion resonance radiation for Ca, Ba, Zn, Mg, Sr, Yb, and Eu

Radiative Lifetimes And Alignment Depolarization Cross Sections For YbI And II By The Hanle Effect In A Flowing Helium System

The radiative lifetimes of the 17992-,25068-,28857-, 37414-, 40564-, and 44017-cm-1 neutral levels and the 30392-cm-1 ion level of Yb have been measured by the Hanle method in a fast-flowing He system. The lifetimes (in units of 10-9 sec) were found to be 820(20), 5.12(0.12), 14.4(0.4), 77.4(6.0), 9.32(0.6), 39.1(3.5), and 5.8(0.6), respectively. In a flowing system with He as a buffer gas the alignment depolarization cross sections with Yb were obtained and are reported here for the first time. They are (in units of 10-15 cm2) 5.0(1.0), 5.9(1.0), 5.9(1.2), 17.9(2.0), 28.2(3.0), 5.16(4.0), and 7.2(2.5), respectively. © 1976 The American Physical Society

Emerging single cell endothelial heterogeneity supports sprouting tumour angiogenesis and growth

Blood vessels supplying tumors are often dysfunctional and generally heterogeneous. The mechanisms underlying this heterogeneity remain poorly understood. Here, using multicolor lineage tracing, in vivo time-lapse imaging and single cell RNA sequencing in a mouse glioma model, we identify tumour-specific blood endothelial cells that originate from cells expressing the receptor for colony stimulating factor 1, Csf1r, a cytokine which controls macrophage biology. These Csf1r lineage endothelial cells (CLECs) form up to 10% of the tumour vasculature and express, besides classical blood endothelial cell markers, a gene signature that is distinct from brain endothelium but shares similarities with lymphatic endothelial cell populations. in silico analysis of pan-cancer single cell RNAseq datasets highlights the presence of a comparable subpopulation in the endothelium of a wide spectrum of human tumours. We show that CLECs actively contribute to sprouting and remodeling of tumour blood vessels and that selective depletion of CLECs reduces vascular branching and tumour growth. Our findings indicate that a non-tumour resident Csf1r-positive population is recruited to tumours, differentiates into blood endothelial cells to contribute to vascularization and, thereby, tumour growth

Expression of VjbR under Nutrient Limitation Conditions Is Regulated at the Post-Transcriptional Level by Specific Acidic pH Values and Urocanic Acid

VjbR is a LuxR homolog that regulates transcription of many genes including important virulence determinants of the facultative intracellular pathogen Brucella abortus. This transcription factor belongs to a family of regulators that participate in a cell-cell communication process called quorum sensing, which enables bacteria to respond to changes in cell population density by monitoring concentration of self produced autoinducer molecules. Unlike almost all other LuxR-type proteins, VjbR binds to DNA and activates transcription in the absence of any autoinducer signal. To investigate the mechanisms by which Brucella induces VjbR-mediated transcriptional activation, and to determine how inappropriate spatio-temporal expression of the VjbR target genes is prevented, we focused on the study of expression of vjbR itself. By assaying different parameters related to the intracellular lifestyle of Brucella, we identified a restricted set of conditions that triggers VjbR protein expression. Such conditions required the convergence of two signals of different nature: a specific pH value of 5.5 and the presence of urocanic acid, a metabolite involved in the connection between virulence and metabolism of Brucella. In addition, we also observed an urocanic acid, pH-dependent expression of RibH2 and VirB7, two additional intracellular survival-related proteins of Brucella. Analysis of promoter activities and determination of mRNA levels demonstrated that the urocanic acid-dependent mechanisms that induced expression of VjbR, RibH2, and VirB7 act at the post-transcriptional level. Taken together, our findings support a model whereby Brucella induces VjbR-mediated transcription by modulating expression of VjbR in response to specific signals related to the changing environment encountered within the host

G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells

<p>Abstract</p> <p>Background</p> <p>Tazarotene-induced gene 1 (TIG1) is a retinoid-inducible type II tumour suppressor gene. The B isoform of TIG1 (TIG1B) inhibits growth and invasion of cancer cells. Expression of TIG1B is frequently downregulated in various cancer tissues; however, the expression and activities of the TIG1A isoform are yet to be reported. Therefore, this study investigated the effects of the TIG1A and TIG1B isoforms on cell growth and gene expression profiles using colon cancer cells.</p> <p>Methods</p> <p>TIG1A and TIG1B stable clones derived from HCT116 and SW620 colon cancer cells were established using the GeneSwitch system; TIG1 isoform expression was induced by mifepristone treatment. Cell growth was assessed using the WST-1 cell proliferation and colony formation assays. RNA interference was used to examine the TIG1 mediating changes in cell growth. Gene expression profiles were determined using microarray and validated using real-time polymerase chain reaction, and Western blot analyses.</p> <p>Results</p> <p>Both TIG1 isoforms were expressed at high levels in normal prostate and colon tissues and were downregulated in colon cancer cell lines. Both TIG1 isoforms significantly inhibited the growth of transiently transfected HCT116 cells and stably expressing TIG1A and TIG1B HCT116 and SW620 cells. Expression of 129 and 55 genes was altered upon induction of TIG1A and TIG1B expression, respectively, in stably expressing HCT116 cells. Of the genes analysed, 23 and 6 genes were upregulated and downregulated, respectively, in both TIG1A and TIG1B expressing cells. Upregulation of the G-protein-coupled receptor kinase 5 (GRK5) was confirmed using real-time polymerase chain reaction and Western blot analyses in both TIG1 stable cell lines. Silencing of TIG1A or GRK5 expression significantly decreased TIG1A-mediated cell growth suppression.</p> <p>Conclusions</p> <p>Expression of both TIG1 isoforms was observed in normal prostate and colon tissues and was downregulated in colon cancer cell lines. Both TIG1 isoforms suppressed cell growth and stimulated GRK5 expression in HCT116 and SW620 cells. Knockdown of GRK5 expression alleviated TIG1A-induced growth suppression of HCT116 cells, suggesting that GRK5 mediates cell growth suppression by TIG1A. Thus, TIG1 may participate in the downregulation of G-protein coupled signaling by upregulating GRK5 expression.</p

Global Analysis of Quorum Sensing Targets in the Intracellular Pathogen Brucella melitensis 16 M

Many pathogenic bacteria use a regulatory process termed quorum sensing (QS) to produce and detect small diffusible molecules to synchronize gene expression within a population. In Gram-negative bacteria, the detection of, and response to, these molecules depends on transcriptional regulators belonging to the LuxR family. Such a system has been discovered in the intracellular pathogen Brucella melitensis, a Gram-negative bacterium responsible for brucellosis, a worldwide zoonosis that remains a serious public health concern in countries were the disease is endemic. Genes encoding two LuxR-type regulators, VjbR and BabR, have been identified in the genome of B. melitensis 16 M. A DeltavjbR mutant is highly attenuated in all experimental models of infection tested, suggesting a crucial role for QS in the virulence of Brucella. At present, no function has been attributed to BabR. The experiments described in this report indicate that 5% of the genes in the B. melitensis 16 M genome are regulated by VjbR and/or BabR, suggesting that QS is a global regulatory system in this bacterium. The overlap between BabR and VjbR targets suggest a cross-talk between these two regulators. Our results also demonstrate that VjbR and BabR regulate many genes and/or proteins involved in stress response, metabolism, and virulence, including those potentially involved in the adaptation of Brucella to the oxidative, pH, and nutritional stresses encountered within the host. These findings highlight the involvement of QS as a major regulatory system in Brucella and lead us to suggest that this regulatory system could participate in the spatial and sequential adaptation of Brucella strains to the host environment.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Skeletal Muscle Phenotypically Converts and Selectively Inhibits Metastatic Cells in Mice

Skeletal muscle is rarely a site of malignant metastasis; the molecular and cellular basis for this rarity is not understood. We report that myogenic cells exert pronounced effects upon co-culture with metastatic melanoma (B16-F10) or carcinoma (LLC1) cells including conversion to the myogenic lineage in vitro and in vivo, as well as inhibition of melanin production in melanoma cells coupled with cytotoxic and cytostatic effects. No effect is seen with non-tumorigenic cells. Tumor suppression assays reveal that the muscle-mediated tumor suppressor effects do not generate resistant clones but function through the down-regulation of the transcription factor MiTF, a master regulator of melanocyte development and a melanoma oncogene. Our findings point to skeletal muscle as a source of therapeutic agents in the treatment of metastatic cancers

Microplanning with Communicative Intentions: The SPUD System

The process of microplanning in Natural Language Generation (NLG) encompasses a range of problems in which a generator must bridge underlying domain-specific representations and general linguistic representations. These problems include constructing linguistic referring expressions to identify domain objects, selecting lexical items to express domain concepts, and using complex linguistic constructions to concisely convey related domain facts. In this paper, we argue that such problems are best solved through a uniform, comprehensive, declarative process. In our approach, the generator directly explores a search space for utterances described by a linguistic grammar. At each stage of search, the generator uses a model of interpretation, which characterizes the potential links between the utterance and the domain and context, to assess its progress in conveying domain-specific representations. We further address the challenges for implementation and knowledge representation in this approach. We show how to implement this approach effectively by using the lexicalized tree-adjoining grammar formalism (LTAG) to connect structure to meaning and using modal logic programming to connect meaning to context. We articulate a detailed methodology for designing grammatical and conceptua