Liver colonization competence governs colon cancer metastasis.

Tumors that metastasize do so to preferred target organs. To explain this apparent specificity, Paget, > 100 years ago, formulated his seed and soil hypothesis; i.e., the cells from a given tumor would "seed'' only favorable "soil'' offered by certain groups. The hypothesis implies that cancer cells must find a suitable "soil'' in a target organ--i.e., one that supports colonization--for metastasis to occur. We demonstrate in this report that ability of human colon cancer cells to colonize liver tissue governs whether a particular colon cancer is metastatic. In the model used in this study, human colon tumors are transplanted into the nude mouse colon as intact tissue blocks by surgical orthotopic implantation. These implanted tumors closely simulate the metastatic behavior of the original human patient tumor and are clearly metastatic or nonmetastatic to the liver. Both classes of tumors were equally invasive locally into tissues and blood vessels. However, the cells from each class of tumor behave very differently when directly injected into nude mouse livers. Only cells from metastasizing tumors are competent to colonize after direct intrahepatic injection. Also, tissue blocks from metastatic tumors af fixed directly to the liver resulted in colonization, whereas no colonization resulted from nonmetastatic tumor tissue blocks even though some growth occurred within the tissue block itself. Thus, local invasion (injection) and even adhesion to the metastatic target organ (blocks) are not sufficient for metastasis. The results suggest that the ability to colonize the liver is the governing step in the metastasis of human colon cancer.

Parvovirus B19 promoter at map unit 6 confers autonomous replication competence and erythroid specificity to adeno-associated virus 2 in primary human hematopoietic progenitor cells.

The pathogenic human parvovirus B19 is an autonomously replicating virus with a remarkable tropism for human erythroid progenitor cells. Although the target cell specificity for B19 infection has been suggested to be mediated by the erythrocyte P-antigen receptor (globoside), a number of nonerythroid cells that express this receptor are nonpermissive for B19 replication. To directly test the role of expression from the B19 promoter at map unit 6 (B19p6) in the erythroid cell specificity of B19, we constructed a recombinant adeno-associated virus 2 (AAV), in which the authentic AAV promoter at map unit 5 (AAVp5) was replaced by the B19p6 promoter. Although the wild-type (wt) AAV requires a helper virus for its optimal replication, we hypothesized that inserting the B19p6 promoter in a recombinant AAV would permit autonomous viral replication, but only in erythroid progenitor cells. In this report, we provide evidence that the B19p6 promoter is necessary and sufficient to impart autonomous replication competence and erythroid specificity to AAV in primary human hematopoietic progenitor cells. Thus, expression from the B19p6 promoter plays an important role in post-P-antigen receptor erythroid-cell specificity of parvovirus B19. The AAV-B19 hybrid vector system may also prove to be useful in potential gene therapy of human hemoglobinopathies.

An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae.

Competence for genetic transformation in Streptococcus pneumoniae has been known for three decades to arise in growing cultures at a critical cell density, in response to a secreted protease-sensitive signal. We show that strain CP1200 produces a 17-residue peptide that induces cells of the species to develop competence. The sequence of the peptide was found to be H-Glu-Met-Arg-Leu-Ser-Lys-Phe-Phe-Arg-Asp-Phe-Ile-Leu-Gln-Arg- Lys-Lys-OH. A synthetic peptide of the same sequence was shown to be biologically active in small quantities and to extend the range of conditions suitable for development of competence. Cognate codons in the pneumococcal chromosome indicate that the peptide is made ribosomally. As the gene encodes a prepeptide containing the Gly-Gly consensus processing site found in peptide bacteriocins, the peptide is likely to be exported by a specialized ATP-binding cassette transport protein as is characteristic of these bacteriocins. The hypothesis is presented that this transport protein is encoded by comA, previously shown to be required for elaboration of the pneumococcal competence activator.

Role of pili and the phase-variable PilC protein in natural competence for transformation of Neisseria gonorrhoeae.

The Gram-negative bacterial pathogen Neisseria gonorrhoeae is naturally competent for transformation with species-related DNA. We show here that two phase-variable pilus-associated proteins, the major pilus subunit (pilin, or PilE) and PilC, a factor known to function in the assembly and adherence of gonococcal pili, are essential for transformation competence. The PilE and PilC proteins are necessary for the conversion of linearized plasmid DNA carrying the Neisseria-specific DNA uptake signal into a DNase-resistant form. The biogenesis of typical pilus fibers is neither essential nor sufficient for this process. DNA uptake deficiency of defined piliated pilC1,2 double mutants can be complemented by expression of a cloned pilC2 gene in trans. The PilC defect can also be restored by the addition of purified PilC protein, or better, pili containing PilC protein, to the mutant gonococci. Our data suggest that the two phase-variable Pil proteins act on the bacterial cell surface and cooperate in DNA recognition and/or outer membrane translocation.

Competence for collagenase gene expression by tissue fibroblasts requires activation of an interleukin 1 alpha autocrine loop.

The enzyme collagenase (EC 3.4.24.7), a key mediator in biological remodeling, can be induced in early-passage fibroblasts by a wide variety of agents and conditions. In contrast, at least some primary tissue fibroblasts are incompetent to synthesize collagenase in response to many of these stimulators. In this study, we investigate mechanisms controlling response to two of the conditions in question: (i) trypsin or cytochalasin B, which disrupt actin stress fibers, or (ii) phorbol 12-myristate 13-acetate (PMA), which activates growth factor signaling pathways. We demonstrate that collagenase expression stimulated by trypsin or cytochalasin B is regulated entirely through an autocrine cytokine, interleukin 1 alpha (IL-1 alpha). The IL-1 alpha intermediate also constitutes the major mechanism by which PMA stimulates collagenase expression, although a second signaling pathway(s) contributes to a minor extent. Elevation of the IL-1 alpha level in response to stimulators is found to be sustained by means of an autocrine feedback loop in early-passage fibroblast cultures. In contrast, fibroblasts freshly isolated from the tissue are incompetent to activate and sustain the IL-1 alpha feedback loop, even though they synthesize collagenase in response to exogenous IL-1. We conclude that this is the reason why tissue fibroblasts are limited, in comparison with subcultured fibroblasts, in their capacity to synthesize collagenase. Activation of the IL-1 alpha feedback loop, therefore, seems likely to be an important mechanism by which resident tissue cells adopt the remodeling phenotype.

Competence profile differences among graduates from different academic subject fields: implications for improving students’ education

The aim of a university education is the intellectual development of citizens, and the training of professionals for their subsequent entry into the workforce. However, this entry into the workforce, following the theoretical education usually provided by the university, implies that students have to manage this difficult transition by themselves. Society, in a continual process of transformation, requires of universities that they adjust, adapting the education they offer to comply with the demands of society and the workplace. Socio-emotional skills would seem to have influence predicting professional performance. These skills also influence job-finding and employability. Consequently, providing teachers with an education in socioemotional competences is becoming a necessary task within universities, and the majority of teaching staff consider these skills to be fundamental to the personal and socio-emotional development of students. The objective of our proposed work is to establish the characteristic profile of competences of a sample of teachers in training, and compare it with the competences profile of graduate students belonging to the fields of law sciences, social sciences, humanities, science and technology, and health. Starting from results, implications will be derived for the development of generic competences of socio-emotional type in the framework of the European Frame of Higher Education.

Differences in exposure to occupational health risks in Spanish and foreign-born workers in Spain (Itsal Project)

Migrant workers usually show higher rates of work-related health problems than natives. However, little information is available about their exposure to occupational risks. We describe self-reported working exposure in Spanish and foreign-born workers. A cross-sectional survey was conducted as part of the ITSAL Project. Data on sociodemographic and self-reported occupational exposure in 1,841 foreign-born and 509 Spanish workers were collected through face-to-face interviews. Prevalence and adjusted odds ratios-aOR- (by age, education, type of contract) were calculated. Foreign-born men in non-services sectors and those in manual occupations perceived exposure to occupational risks with lower prevalence than Spanish workers. Foreign-born women reported higher prevalence of exposure than Spanish female workers. By occupation, foreign-born female workers were more likely than Spanish workers to report working many hours/day (aOR2.68; 95 % CI 1.06–6.78) and exposure to extreme temperatures (aOR2.19; 95 % CI 1.10–4.38). Some groups of migrant workers may need increased protection regarding some occupational exposures.

Prevalence of exposure to occupational risks during preganancy in Spain

Objectives. We describe reported exposures to main categories of occupational agents and conditions in Spanish pregnant workers. Methods. Women were recruited at 12th week of pregnancy from main public gynaecological consults to be included in the INMA Spanish cohorts study (n = 2,058). Through personal interviews with structured questionnaires, information on working situation and working conditions during pregnancy was obtained. Results. Fifty percent of the women reported frequent exposure to physical load (standing, heavy lifting) and 45 % reported exposure to three or more indicators of job strain. Exposure to at least one physical agent (noise, vibrations, etc.) affected 25 % of the women. Exposure to chemicals was reported by 20 % of the women, mostly including solvents and cleaning products. Eight percent of the women worked at night shifts. Job strain was more prevalent in office workers and industrial operators. Industrial workers showed the highest prevalence of exposure to chemical and physical pollutants. Conclusions. Our data suggest that working conditions of pregnant women may need increased control in Spain.

Environmental and Occupational Optometry. Lesson 2 (Course 2013-2014)

Tema 2. Actividad voluntaria nº 2.

Environmental and Occupational Optometry. Lesson 3 (Course 2013-2014)

Tema 3. Actividad evaluable nº 2.

Environmental and Occupational Optometry. Lesson 4 (Course 2013-2014)

Tema 4. Actividad voluntaria nº 2.

Environmental and Occupational Optometry. Lesson 5 (Course 2013-2014)

Tema 5. Actividad voluntaria nº 3.

Environmental and Occupational Optometry. Lesson 6 (Course 2013-2014)

Tema 6: Diseño del entorno visual. Actividad propuesta no. 3.