100,118 research outputs found

    Membrane topology of the ArsB protein, the membrane subunit of an anion-translocating ATPase

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    The ars operon of the conjugative R-factor R773 encodes an oxyanion pump that catalyzes extrusion of arsenicals from cells of Escherichia coli. The oxyanion translocation ATPase is composed of two polypeptides, the catalytic ArsA protein and the intrinsic membrane protein, ArsB. The topology of regions of the ArsB protein in the inner membrane was determined using a variety of gene fusions. Random gene fusions with lacZ and phoA were generated using transposon mutagenesis. A series of gene fusions with blaM were constructed in vitro using a beta-lactamase fusion vector. To localize individual segments of the ArsB protein, a ternary fusion method was developed, where portions of the arsB gene were inserted in-frame between the coding regions for two heterologous proteins, in this case a portion of a newly identified arsD gene and the blaM sequence encoding the mature beta-lactamase. The location of a periplasmic loop was determined from V8 protease digestion of an ArsA-ArsB chimera. From analysis of data from 26 fusions, a topological model of the ArsB protein with 12 membrane-spanning regions is proposed

    The Novel ''Controlled Intermediate Nuclear Fusion'' and its Possible Industrial Realization as Predicted by Hadronic Mechanics and Chemistry

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    In this note, we propose, apparently for the first time, a new type of controlled nuclear fusion called "intermediate" because occurring at energies intermediate between those of the ''cold'' and ''hot'' fusions, and propose a specific industrial realization. For this purpose: 1) We show that known limitations of quantum mechanics, quantum chemistry and special relativity cause excessive departures from the conditions occurring for all controlled fusions; 2) We outline the covering hadronic mechanics, hadronic chemistry and isorelativity specifically conceived, constructed and verified during the past two decades for new cleans energies and fuels; 3) We identify seven physical laws predicted by the latter disciplines that have to be verified by all controlled nuclear fusions to occur; 4) We review the industrial research conducted to date in the selection of the most promising engineering realization as well as optimization of said seven laws; and 5) We propose with construction details a specific {\it hadronic reactor} (patented and international patents pending), consisting of actual equipment specifically intended for the possible industrial production of the clean energy released by representative cases of controlled intermediate fusions for independent scrutiny by interested colleagues.Comment: 32 pages, 5 figures. Journal of Applied Sciences, in pres

    Regional perturbation of gene transcription is associated with intrachromosomal rearrangements and gene fusion transcripts in high grade ovarian cancer.

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    Genomic rearrangements are a hallmark of cancer biology and progression, allowing cells to rapidly transform through alterations in regulatory structures, changes in expression patterns, reprogramming of signaling pathways, and creation of novel transcripts via gene fusion events. Though functional gene fusions encoding oncogenic proteins are the most dramatic outcomes of genomic rearrangements, we investigated the relationship between rearrangements evidenced by fusion transcripts and local expression changes in cancer using transcriptome data alone. 9,953 gene fusion predictions from 418 primary serious ovarian cancer tumors were analyzed, identifying depletions of gene fusion breakpoints within coding regions of fused genes as well as an N-terminal enrichment of breakpoints within fused genes. We identified 48 genes with significant fusion-associated upregulation and furthermore demonstrate that significant regional overexpression of intact genes in patient transcriptomes occurs within 1 megabase of 78 novel gene fusions that function as central markers of these regions. We reveal that cancer transcriptomes select for gene fusions that preserve protein and protein domain coding potential. The association of gene fusion transcripts with neighboring gene overexpression supports rearrangements as mechanism through which cancer cells remodel their transcriptomes and identifies a new way to utilize gene fusions as indicators of regional expression changes in diseased cells with only transcriptomic data

    Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

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    The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs) that can reduce the tumor mass. Dendritic cells (DCs) are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.Grants-in-Aid for Scientific Research from the Ministry of Education, Cultures, Sports, Science and Technology of Japan, Grant-in-Aid of the Japan Medical Association, Takeda Science Foundation, Pancreas Research Foundation of Japan, The Promotion and Mutual Aid Corporation for Private School of Japan and Foundation for Promotion of Cancer Researc

    The Amino Terminus of the Yeast F_1-ATPase β-Subunit Precursor Functions as a Mitochondrial Import Signal

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    The ATP2 gene of Saccharomyces cerevisiae codes for the cytoplasmically synthesized beta-subunit protein of the mitochondrial F1-ATPase. To define the amino acid sequence determinants necessary for the in vivo targeting and import of this protein into mitochondria, we have constructed gene fusions between the ATP2 gene and either the Escherichia coli lacZ gene or the S. cerevisiae SUC2 gene (which codes for invertase). The ATP2-lacZ and ATP2-SUC2 gene fusions code for hybrid proteins that are efficiently targeted to yeast mitochondria in vivo. The mitochondrially associated hybrid proteins fractionate with the inner mitochondrial membrane and are resistant to proteinase digestion in the isolated organelle. Results obtained with the gene fusions and with targeting-defective ATP2 deletion mutants provide evidence that the amino-terminal 27 amino acids of the beta-subunit protein precursor are sufficient to direct both specific sorting of this protein to yeast mitochondria and its import into the organelle. Also, we have observed that certain of the mitochondrially associated Atp2-LacZ and Atp2-Suc2 hybrid proteins confer a novel respiration-defective phenotype to yeast cells

    Association schemes from the action of PGL(2,q)PGL(2,q) fixing a nonsingular conic in PG(2,q)

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    The group PGL(2,q)PGL(2,q) has an embedding into PGL(3,q)PGL(3,q) such that it acts as the group fixing a nonsingular conic in PG(2,q)PG(2,q). This action affords a coherent configuration R(q)R(q) on the set L(q)L(q) of non-tangent lines of the conic. We show that the relations can be described by using the cross-ratio. Our results imply that the restrictions R+(q)R_{+}(q) and R(q)R_{-}(q) to the sets L+(q)L_{+}(q) of secant lines and to the set L(q)L_{-}(q) of exterior lines, respectively, are both association schemes; moreover, we show that the elliptic scheme R(q)R_{-}(q) is pseudocyclic. We further show that the coherent configuration R(q2)R(q^2) with qq even allow certain fusions. These provide a 4-class fusion of the hyperbolic scheme R+(q2)R_{+}(q^2), and 3-class fusions and 2-class fusions (strongly regular graphs) of both schemes R+(q2)R_{+}(q^2) and $R_{-}(q^2). The fusion results for the hyperbolic case are known, but our approach here as well as our results in the elliptic case are new.Comment: 33 page