Laminin 10/11: an alternative adhesive ligand for epidermal keratinocytes with a functional role in promoting proliferation and migration

We have investigated the expression and function of the isoforms of laminin bearing the alpha(5) chain, i.e. laminin-10/11 in neonatal and adult human skin. By immunostaining human skin derived from a variety of anatomic sites, we found that the laminin-alpha(5) chain is expressed abundantly in the basement membrane underlying the interfollicular epidermis and the blood vessels in the dermis. Interestingly, while the expression level of the well-studied laminin-5 isoform did not change significantly with age, laminin-10/11 (a5 chain) appeared to decrease in the basement membrane underlying the epidermis, in adult skin. In contrast, the levels of laminin-10/11 in the basement membrane underlying blood vessels remained unchanged in neonatal vs. adult skin. Importantly, in vitro cell adhesion assays demonstrated that laminin-10/11 is a potent adhesive substrate for both neonatal and adult keratinocytes and that this adhesion is mediated by the alpha(3)beta(1), and alpha(6)beta(4) integrins. Adhesion assays performed with fractionated basal keratinocytes showed that stem cells, transit amplifying cells and early differentiating cells all adhere to purified laminin-10/11 via these receptors. Further, laminin-10/11 provided a proliferative signal for neonatal foreskin keratinocytes, adult breast skin keratinocytes, and even a human papillomavirus type-18 transformed tumorigenic keratinocyte cell line in vitro. Finally, laminin-10/11 was shown to stimulate keratinocyte migration in an in vitro wound healing assay. These results provide strong evidence for a functional role for laminin-10/11 in epidermal proliferation during homeostasis, wound healing and neoplasia.

9,10-Dihydroxy-1,8-cineole (1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octane-10,11-diol)

The title compound (3) has been synthesized and its presence sought in the urinary metabolites of the brushtail possum. © CSIRO 2001

Hydrolytic kinetic resolution of terminal mono- and bis-epoxides in the synthesis of insect pheromones: routes to (-)-(R)- and (+)-(S)-10-methyldodecyl acetate, (-)-(R)-10-methyl-2-tridecanone, (-)-(R)-(Z)-undec-6-en-2-ol (Nostrenol), (-)-(1R,7R)-1,7-dime

Hydrolytic kinetic resolution (HKR) of functionalised epoxides using (salen)Co(OAc) complexes provides enantiomerically enriched epoxides and diols, which have been transformed into important insect sex pheromones. In this general approach, (-)-(R)- and (+)-(S)-10-methyldodecyl acetates from the smaller tea tortrix moth were obtained, as was (-)-(R)-10-methyltridecan-2-one from the southern corn rootworm. The (S)-epoxide obtained from undec-1-en-6-yne was transformed to (-)-(R)-(Z)-undec-6-en-2-ol (Nostrenol) from ant-lions. HKR of appropriate bisepoxides was also investigated, and transformations of the resulting bisepoxides and epoxydiols provided (-)-(1R,7R)-1,7-dimethylnonylpropanoate from corn rootworms, (-)-(6R,12R)-6,12-dimethylpentadecan-2-one from the female banded cucumber beetle, and (-)-(2S,11S)-2,11-diacetoxytridecane and (+)-(2S,12S)-2,12-diacetoxytridecane from female pea-midges. (C) 2002 Elsevier Science Ltd. All rights reserved.

Occult Axillary Lymph Node Metastases in Breast Cancer Do Matter: Results of 10-Year Survival Analysis

Axillary lymph node status is one of the most powerful prognostic factors for patients with breast cancer and is often critical in stratifying patients into adjuvant treatment regimens. In 203 apparently node-negative cases of breast cancer, a combination of immunohistochemical staining and step-sectioning identified occult metastases in 25% of cases. Ten-year follow-up information is available for these patients. Histologic features of the primary tumor and immunohistochemical staining for estrogen receptor, progesterone receptor, Her-2, and p53 were also evaluated. With multivariate analysis, both occult metastases and higher histologic grade of the primary tumor were independent predictors of disease-free survival. Histologic grade was the only significant independent predictor of overall survival. Estrogen receptor, progesterone receptor, Her-2, and p53 status did not predict the presence of metastases or survival when all tumor types were considered together. Metastases >0.5 mm significantly predicted a poorer disease-free survival when invasive ductal carcinomas were considered alone. Histologic grade was significantly associated with disease-free survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients. The presence of occult metastases approached significance for overall survival in the premenopausal and perimenopausal patients but not in the postmenopausal patients.

Longitudinal study of veterinarians from entry to the veterinary course to 10 years after graduation: attitudes to work, career and profession

Objective To describe the attitudes of veterinarians to their work, career and profession during the 10 years after graduation. Design Longitudinal study of students who started their course at The University of Queensland in 1985 and 1986, and who completed questionnaires in their first and fifth year as students, and after one, five and 10 years as veterinarians. Methods Data from 129 (96%) questionnaires completed after 10 years as a veterinarian were coded numerically then analysed, together with data from previous questionnaires, with SAS System 7 for Windows 95. Results After 10 years, almost all respondents were either very glad they had done the veterinary course (57%) or generally glad, though with some misgivings (37%). Despite this, only 55% would definitely become a veterinarian if they 'had to do it over again'. The responses for about one-third were different from those given five years earlier. The views of many were related to the level of support and encouragement received in their first job after graduation. There were 42% who were working less than half-time as veterinarians, and their main reasons were, in order, raising children, long hours of work, attitudes of bosses and clients, and poor pay. A majority was concerned about the ethics and competence of some colleagues, and almost all believed that consideration of costs must influence the type of treatment animals receive. Conclusions Most veterinarians were glad to have done the veterinary course, but for about one-quarter their career had not lived up to expectations and almost half would not do it again in another incarnation. Stress, hours of work, difficulties in balancing personal life with career and low income were important concerns for many. Low income may contribute to the low number of males entering the veterinary profession.

4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes from the cane beetle Antitrogus parvulus - Cuticular hydrocarbons with unprecedented structure and stereochemistry

[GRAPHICS] The major cuticular hydrocarbons from the cane beetle species Antitrogus parvulus were deduced to be 4,6,8,10,16,18-hexa- and 4,6,8,10,16-pentamethyldocosanes 2 and 3, respectively. Isomers of 2,4,6,8-tetramethylundecanal 27, 36, and 37, derived from 2,4,6-trimethylphenol, were coupled with the phosphoranes 28 and 29 to furnish alkenes and, by reduction, diastereomers of 2 and 3. Chromatographic and spectroscopic comparisons confirmed 2 as either 6a or 6b and 3 as either 34a or 34b.

Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10

Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. ReIB activation is required for myeloid DC differentiation. Here, we show that antigen-exposed DCs in which ReIB function is inhibited lack cell surface CD40, prevent priming of immunity, and suppress previously primed immune responses. DCs generated from CD40-deficient mice similarly confer suppression. Regulatory CD4(+) T cells induced by the DCs transfer antigen-specific Infectious tolerance to primed recipients in an interleukin10-dependent fashion. Thus CD40, regulated by ReIB activity, determines the consequences of antigen presentation by myeloid DCs. These observations have significance for autoimmune immunotherapy and suggest a mechanism by which peripheral tolerance might be constitutively maintained by RelB(-) CD40(-) DCs.

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Priming to Ag can inhibit subsequent induction of an immune response to a new epitope incorporated into that Ag, a phenomenon referred to as original antigenic sin. In this study, we show that prior immunity to a virus capsid can inhibit subsequent induction of the IFN-gamma effector T cell response to a novel CD8-restricted antigenic epitope associated with the virus capsid. Inhibition does not involve Ab to the virus capsid, as it is observed in animals lacking B cells. CD8-restricted virus-specific T cell responses are not required, as printing to virus without CTL induction is associated with inhibition. However, IL-10(-/-) mice, in contrast to IL-10(+/+) mice, generate CD8 T cell and Ab responses to novel epitopes incorporated into a virus capsid, even when priming to the capsid has resulted in high titer Ab to the capsid. Furthermore, capsid-primed mice, unable to mount a response to a novel epitope in the capsid protein, are nevertheless able to respond to the same novel epitope delivered independently of the capsid. Thus, inhibition of responsiveness to a novel epitope in a virus-primed animal is a consequence of secretion of IL-10 in response to presented Ag, which inhibits local generation of new CD8 IFN-gamma-secreting effector T cells. Induction of virus- or tumor Ag-specific CD8 effector T cells in the partially Ag-primed host may thus be facilitated by local neutralization of IL-10.

A????es premiadas no 10?? Concurso Inova????o na Gest??o P??blica Federal

A publica????o apresenta o relato das 20 experi??ncias premiadas no 10?? Concurso Inova????o na Gest??o P??blica Federal e ?? uma importante fonte de refer??ncia de solu????es concretas para problemas enfrentados no dia-a-dia da administra????o p??blica. Nesta publica????o, o leitor encontrar?? iniciativas inovadoras nas seguintes ??reas: articula????o de parcerias, avalia????o de desempenho institucional, avalia????o e monitoramento de pol??ticas p??blicas, estabelecimento de padr??es de atendimento de servi??os, gerenciamento de pessoas e capacita????o, gerenciamento de informa????es, implementa????o de melhoria cont??nua, planejamento e gest??o estrat??gica, simplifica????o e agiliza????o de procedimentos

Texto para discuss??o 10: qual Estado?

A Constitui????o de 1988 modelou um Estado nacional grande e fr??gil. Constitucionalmente, grande empreendedor econ??mico e banqueiro, mas fr??gil porque sem condi????es para insistir no rumo estatizante anterior, contr??rio ?? tend??ncia vigente no atual crep??sculo dos ide??rios coletivistas. Constitucionalmente, grande respons??vel pela felicidade social do povo, mas fr??gil porque a Uni??o (a grande protagonista do Estado brasileiro) ?? prejudicada pelas sangrias e vincula????es que a constrangem, pelo desequil??brio entre autoridade e responsabilidade dos Poderes, pelas imperfei????es da Federa????o e pelas mazelas do servi??o p??blico. Os resultados s??o insufici??ncias claras no que ?? inerente ao Estado nacional: seguran??a e defesa, infra-estrutura transregional (energia, transportes, comunica????es), algumas responsabilidades sociais (previd??ncia b??sica, sa??de, educa????o, saneamento, habita????o), rela????es internacionais, ci??ncia e tecnologia e poder normativo, fiscalizador, mediador e sinalizador de rumos s??cio-econ??micos (sinaliza????o exigente de instrumentos de est??mulo que dependem de recursos).

M??dulo 10 - habilita????o dos interessados: curso legisla????o aplicada ?? log??stica de suprimentos lei n?? 8.666/93, preg??o e registro de pre??os

Este documento trata de: aspectos conceituais da lei: finalidade, import??ncia e hierarquia da lei; no????es gerais da lei de licita????es - Lei n?? 8.666/93; tipos de licita????o: menor pre??o, melhor t??cnica, t??cnica e pre??o e maior lance ou oferta; modalidades de licita????o: concorr??ncia, tomada de pre??os, convite, concurso e leil??o; exce????es ?? obrigatoriedade de licita????o: dispensa e inexigibilidade; regime de execu????o indireta; comiss??o de licita????o; etapas do processo licitat??rio: edital, procedimentos/documentos do certame, registro cadastral, habilita????o dos interessados, julgamento e encerramento; preg??o; registro de pre??os