Negative regulators of a growth factor-mediated signaling pathway in the nematode Caenorhabditis elegans

Vulval differentiation in C. elegans is mediated by an Epidermal growth factor (EGF)- EGF receptor (EGFR) signaling pathway. I have cloned unc-101, a negative regulator of vulval differentiation of the nematode C. elegans. unc-101 encodes a homolog of AP47, the medium chain of the trans-Golgi clathrin-associated protein complex. This identity was confirmed by cloning and comparing sequence of a C. elegans homolog of AP50, the medium chain of the plasma membrane clathrin-associated protein complex. I provided the first genetic evidence that the trans-Golgi clathrin-coated vesicles are involved in regulation of an EGF signaling pathway. Most of the unc-101 alleles are deletions or nonsense mutations, suggesting that these alleles severely reduce the unc-101 activity. A hybrid gene that contains parts of unc-101 and mouse AP4 7 rescued at least two phenotypes of unc-101 mutations, the Unc and the suppression of vulvaless phenotype of let-23(sy1) mutation. Therefore, the functions of AP47 are conserved between nematodes and mammals.

unc-101 mutations can cause a greater than wild-type vulval differentiation in combination with certain mutations in sli-1, another negative regulator of the vulval induction pathway. A mutation in a new gene, rok-1, causes no defect by itself, but causes a greater than wild-type vulval differentiation in the presence of a sli-1 mutation. The unc-101; rok-1; sli-1 triple mutants display a greater extent of vulval differentiation than any double mutant combinations of unc-101, rok-1 and sli-1. Therefore, rok-1 locus defines another negative regulator of the vulval induction pathway.

I analyzed a second gene encoding an AP47 homolog in C. elegans. This gene, CEAP47, encodes a protein 72% identical to both unc-101 and mammalian AP47. A hybrid gene containing parts of unc-101 and CEAP47 sequences can rescue phenotypes of unc-101 mutants, indicating that UNC- 101 and CEAP47 proteins can be redundant if expressed in the same set of cells.

Negative refractive index in a four-level atomic system

We propose a scheme for realizing negative refractive index in a four-level atomic system. It is shown that such a system can simultaneously exhibit negative permittivity and negative permeability in an optical frequency range. Furthermore, by analysing the dispersion property of the left-handed material, we find that the probe beam can be controlled from superluminal to subluminal or vice versa via choosing appropriate parameters.

Phase control of switching from positive to negative index material in a four-level atomic system

Electric and magnetic responses of the medium to the probe field are analysed in a four-level loop atomic system by taking into account the relative phase of the applied fields. An interesting phenomenon is found: under suitable conditions, a change of the refractive index from positive to negative can occur by modulating the relative phase of the applied fields. Then the medium can be switched from a positive index material to a negative index material in our scheme. In addition, a negative index material can be realized in different frequency regions by adjusting the relative phase. It may give us a convenient way to obtain the desired material with positive or negative index.

Negative regulation of transcription factors by Srb10 cyclin-dependent kinase

The ubiquitin-dependent proteolytic pathway plays an important role in a broad array of cellular processes, inducting cell cycle control and transcription. Biochemical analysis of the ubiquitination of Sic1, the B-type cyclin-dependent kinase (CDK) inhibitor in budding yeast helped to define a ubiquitin ligase complex named SCF^cdc4 (for Skp1, Cdc53/cullin, F-box protein). We found that besides Sic1, the CDK inhibitor Far1 and the replication initiation protein Cdc6 are also substrates of SCF^cdc4 in vitro. A common feature in the ubiquitination of the cell cycle SCF^cdc4 substrates is that they must be phosphorylated by the major cell cycle CDK, Cdc28. Gcn4, a transcription activator involved in the general control of amino acid biosynthesis, is rapidly degraded in an SCF^cdc4-dependent manner in vivo. We have focused on this substrate to investigate the generality of the SCF^cdc4 pathway. Through biochemical fractionations, we found that the Srb10 CDK phosphorylates Gcn4 and thereby marks it for recognition by SCF^cdc4 ubiquitin ligase. Srb10 is a physiological regulator of Gcn4 stability because both phosphorylation and turnover of Gcn4 are diminished in srb10 mutants. Furthermore, we found that at least two different CDKs, Pho85 and Srb10, conspire to promote the rapid degradation of Gcn4 in vivo. The multistress response transcriptional regulator Msn2 is also a substrate for Srb10 and is hyperphosphorylated in an Srb10-dependent manner upon heat stress-induced translocation into the nucleus. Whereas Msn2 is cytoplasmic in resting wild type cells, its nuclear exclusion is partially compromised in srb10 mutant cells. Srb10 has been shown to repress a subset of genes in vivo, and has been proposed to inhibit transcription via phosphorylation of the C-terminal domain of RNA polymerase II. Our results suggest a general theme that Srb10 represses the transcription of specific genes by directly antagonizing the transcriptional activators.

Electromagnetically induced negative refractive index in a V-type four-level atomic system

We propose a scheme for realizing negative refractive index in a V-type four-level atomic system. It is shown that the negative refractive index can be achieved in a wide frequency band based on the effect of quantum coherence. It is also found that the frequency band of negative refractive index and the absorption property of left-handed material are manipulated by the pump and control fields. Furthermore, left-handed material with reduced absorption is possible by choosing appropriate parameters. (c) 2006 Elsevier B.V. All rights reserved.

Anomalous behaviour of photorefractive grating erasure owing to existence of both negative and positive carriers

In LiNbO3:Fe, anomalous behaviour of grating erasure is observed with different wavelenghts, i.e. rapid grating erasure in the short wavelength range, which deviates from the results predicted by the electron transport band model. The deviation is related to the coexistance of electrons and holes in photorefraction, and charge-transfer process including electrons and hole has been proposed. The electron and hole contributions to photo-excitation coefficient S of the Fe centre on the wavelength.

An investigation of the reaction negative K¯p → K¯π⁺ at P_(lab) = 2 Gev/c

The reaction K^-p→K^-π⁺n has been studied for incident kaon momenta of 2.0 GeV/c. A sample of 19,881 events was obtained by a measurement of film taken as part of the K-63 experiment in the Berkeley 72 inch bubble chamber.

Based upon our analysis, we have reached four conclusions. (1) The magnitude of the extrapolated Kπ cross section differs by a factor of 2 from the P-wave unitarity prediction and the K⁺n results; this is probably due to absorptive effects. (2) Fits to the moments yield precise values for the Kπ S-wave which agree with other recent statistically accurate experiments. (3) An anomalous peak is present in our backward K^-p→(π+n) K^- u-distribution. (4) We find a non-linear enhancement due to interference similiar to the one found by Bland et al. (Bland 1966).

Negative refraction in a honeycomb-lattice photonic crystal

In this paper we theoretically investigate a photonic crystal with dielectric rods in a honeycomb lattice. Two left-handed frequency regions are found in the second and third photonic band by using the plane wave expansion method to analyze the photonic band structure and equifrequency contours. Subwavelength imaging by the photonic crystal flat lens are systematically studied by numerical simulations using the multiple scattering method. Different from the photonic crystals with noncircular dielectric rods in air, this structure is almost isotropic at the optimal frequency for superlensing. As a comparison, flat slab focusing is also demonstrated at other frequencies in the two left-handed regions. (c) 2006 Elsevier Ltd. All rights reserved.

A sexualidade dos adolescentes que (con)vivem com HIV: implicações para as práticas de cuidado de enfermeiros

Este estudo objetivou compreender a vivência e a sexualidade dos adolescentes que (con)vivem com HIV e indicar possibilidades para as práticas de cuidado realizados pelos enfermeiros. Trata-se de um estudo de natureza descritiva, com abordagem qualitativa, com aproximação na hermenêutica dialética. Foram estudados 20 adolescentes com HIV atendidos em um Hospital Universitário do Rio de Janeiro. Foi utilizada como técnica de coleta de dados entrevistas semi-estruturadas e dois instrumentos de coleta: um questionário de caracterização dos sujeitos e um roteiro temático que guiou as entrevistas. As entrevistas foram gravadas e os conteúdos transcritos e analisados conforme a técnica de análise de conteúdo temática. O resultado evidenciou que o significado da saúde para os sujeitos, numa análise geral, está associado à qualidade de vida e necessidade de manutenção de hábitos saudáveis. Sobre o HIV, destacou-se o desconhecimento sobre o vírus e os modos de transmissão. A vivência com o HIV é marcada predominantemente por sentimentos negativos como medo e sofrimento relacionados com preconceito, estigma e discriminação. Os adolescentes associam a sexualidade ao ato sexual ou orientação sexual. A sexualidade para os adolescentes que adquiriram o vírus através da transmissão sexual também está relacionada às dificuldades com a mesma após a descoberta. Já os adolescentes contaminados por transmissão vertical tiveram como elementos mais presentes a aceitação e conformação da doença. Observar-se a falta de percepção dos adolescentes em relação às práticas de cuidados realizadas pelos enfermeiros, direcionados para minimizar suas necessidades Conclui-se, então, as técnicas de análise utilizadas foram pertinentes, pois permitiram identificar as vivências e os sentidos da sexualidade dos adolescentes que (con)vivem com HIV e a importância das práticas de cuidados de enfermeiros. Este estudo servirá para reflexão crítica para profissionais de saúde, principalmente, enfermeiros, através da identificação e percepção das demandas dos adolescentes com HIV para desenvolver estratégias visando as peculiaridades e necessidades destes adolescentes.