1,793 research outputs found

    Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions

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    Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis

    A balanced Memristor-CMOS ternary logic family and its application

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    The design of balanced ternary digital logic circuits based on memristors and conventional CMOS devices is proposed. First, balanced ternary minimum gate TMIN, maximum gate TMAX and ternary inverters are systematically designed and verified by simulation, and then logic circuits such as ternary encoders, decoders and multiplexers are designed on this basis. Two different schemes are then used to realize the design of functional combinational logic circuits such as a balanced ternary half adder, multiplier, and numerical comparator. Finally, we report a series of comparisons and analyses of the two design schemes, which provide a reference for subsequent research and development of three-valued logic circuits.Comment: 15 pages, 30 figure

    A point mutation in the DNA-binding domain of HPV-2 E2 protein increases its DNA-binding capacity and reverses its transcriptional regulatory activity on the viral early promoter

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    <p>Abstract</p> <p>Background</p> <p>The human papillomavirus (HPV) E2 protein is a multifunctional DNA-binding protein. The transcriptional activity of HPV E2 is mediated by binding to its specific binding sites in the upstream regulatory region of the HPV genomes. Previously we reported a HPV-2 variant from a verrucae vulgaris patient with huge extensive clustered cutaneous, which have five point mutations in its E2 ORF, L118S, S235P, Y287H, S293R and A338V. Under the control of HPV-2 LCR, co-expression of the mutated HPV E2 induced an increased activity on the viral early promoter. In the present study, a series of mammalian expression plasmids encoding E2 proteins with one to five amino acid (aa) substitutions for these mutations were constructed and transfected into HeLa, C33A and SiHa cells.</p> <p>Results</p> <p>CAT expression assays indicated that the enhanced promoter activity was due to the co-expressions of the E2 constructs containing A338V mutation within the DNA-binding domain. Western blots analysis demonstrated that the transiently transfected E2 expressing plasmids, regardless of prototype or the A338V mutant, were continuously expressed in the cells. To study the effect of E2 mutations on its DNA-binding activity, a serial of recombinant E2 proteins with various lengths were expressed and purified. Electrophoresis mobility shift assays (EMSA) showed that the binding affinity of E2 protein with A338V mutation to both an artificial probe with two E2 binding sites or HPV-2 and HPV-16 promoter-proximal LCR sequences were significantly stronger than that of the HPV-2 prototype E2. Furthermore, co-expression of the construct containing A338V mutant exhibited increased activities on heterologous HPV-16 early promoter P97 than that of prototype E2.</p> <p>Conclusions</p> <p>These results suggest that the mutation from Ala to Val at aa 338 is critical for E2 DNA-binding and its transcriptional regulation.</p
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