Development and validation of a framework for the assessment of school curricula on the presence of evolutionary concepts (FACE).

Evolution is a key concept of biology, fundamental to understand the world and address important societal problems, but research studies show that it is still not widely understood and accepted. Several factors are known to influence evolution acceptance and understanding, but little information is available regarding the impacts of the curriculum on these aspects. Very few curricula have been examined to assess the coverage of biological evolution. The available studies do not allow comparative analyses, due to the different methodologies employed by the authors. However, such an analysis would be useful for research purposes and for the development of appropriate educational policies to address the problem of a lack of evolution acceptance in some countries. In this paper we describe the steps through which we developed a valid and reliable instrument for curricula analysis known as FACE: "Framework to Assess the Coverage of biological Evolution by school curricula." This framework was developed based on the "Understanding Evolution Conceptual Framework" (UECF). After an initial pilot study, our framework was reformulated based on identified issues and experts' opinions. To generate validity and reliability evidence in support of the framework, it was applied to four European countries' curricula. For each country, a team of a minimum of two national and two foreign coders worked independently to assess the curriculum using this framework for content analysis. Reliability evidence was estimated using Krippendorf's alpha and resulted in appropriate values for coding the examined curricula. Some issues that coders faced during the analysis were discussed and, to ensure better reliability for future researchers, additional guidelines and one extra category were included in the framework. The final version of the framework includes six categories and 34 subcategories. FACE is a useful tool for the analysis and the comparison of curricula and school textbooks regarding the coverage of evolution, and such results can guide curricula development.

Phenotype of non-c.907_909delGAG mutations in TOR1A: DYT1 dystonia revisited.

BACKGROUND: In addition to the most frequent TOR1A/DYT1 mutation (c.907_909delGAG), a growing number of TOR1A sequence variants are found in dystonia patients. For most, functional characterization has demonstrated pathogenicity at different levels, implying that TOR1A genetic testing should not be limited to screening for c.907_909delGAG. METHODS: We tested 461 Serbian patients with isolated or combined dystonia for changes in the TOR1A gene and performed a systematic literature review of the clinical characteristics of patients carrying TOR1A mutations other than c.907_909delGAG. RESULTS: One likely pathogenic TOR1A mutation (c.385G>A, p.Val129Ile) was detected in an adult-onset cervical dystonia patient. This change is in proximity to the previously reported p.Glu121Lys mutation and predicted to decrease the stability of TOR1A-encoded protein TorsinA. CONCLUSIONS: Our patient and three other reported carriers of non-c.907_909delGAG-mutations within the first three exons of TOR1A showed similar phenotypes of adult-onset focal or segmental cervical dystonia. This observation raises the possibility of genotype-phenotype correlations in DYT1 and indicates that the clinical spectrum of this type of dystonia might be broader then previous classic descriptions.

GPR54 (KISS1R) transactivates EGFR to promote breast cancer cell invasiveness.

Kisspeptins (Kp), peptide products of the Kisspeptin-1 (KISS1) gene are endogenous ligands for a G protein-coupled receptor 54 (GPR54). Previous findings have shown that KISS1 acts as a metastasis suppressor in numerous cancers in humans. However, recent studies have demonstrated that an increase in KISS1 and GPR54 expression in human breast tumors correlates with higher tumor grade and metastatic potential. At present, whether or not Kp signaling promotes breast cancer cell invasiveness, required for metastasis and the underlying mechanisms, is unknown. We have found that kisspeptin-10 (Kp-10), the most potent Kp, stimulates the invasion of human breast cancer MDA-MB-231 and Hs578T cells using Matrigel-coated Transwell chamber assays and induces the formation of invasive stellate structures in three-dimensional invasion assays. Furthermore, Kp-10 stimulated an increase in matrix metalloprotease (MMP)-9 activity. We also found that Kp-10 induced the transactivation of epidermal growth factor receptor (EGFR). Knockdown of the GPCR scaffolding protein, ß-arrestin 2, inhibited Kp-10-induced EGFR transactivation as well as Kp-10 induced invasion of breast cancer cells via modulation of MMP-9 secretion and activity. Finally, we found that the two receptors associate with each other under basal conditions, and FRET analysis revealed that GPR54 interacts directly with EGFR. The stability of the receptor complex formation was increased upon treatment of cells by Kp-10. Taken together, our findings suggest a novel mechanism by which Kp signaling via GPR54 stimulates breast cancer cell invasiveness.

Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium.

Epidemiological and experimental data point to involvement of oxygen derived radicals in the pathogenesis of gynecological disorders, as well as in cancer development. The objective of the present study was to examine changes in activities and levels of copper/zinc superoxide dismutase (CuZnSOD) and lipid hydroperoxides (LOOH) in blood and endometrial tissue of patients diagnosed with uterine myoma, endometrial polypus, hyperplasia simplex, hyperplasia complex and adenocarcinoma endometrii. The results of our study have shown decreased SOD activities and unchanged SOD protein level in blood of all examined patients in comparison to healthy subjects. Decrease of both SOD activity and level was found in endometrium of patients with hyperplasia simplex, hyperplasia complex and adenocarcinoma in comparison to women with polypus or myoma. LOOH level was elevated in both tissues of patients with hyperplasia or adenocarcinoma in comparison to healthy subjects or patients with benign diagnosis. Our findings suggest that the decrease in SOD activity and level, as well as the increase in LOOH level, in patients with gynecological disorders, render these patients more susceptible to oxidative damage caused by reactive oxygen species (ROS). An imbalance in ROS formation and SOD level may be important in the pathogenesis and/or perpetuation of tissue damage in gynecological patients. Since evidence suggests that SOD may be a therapy target for cancer treatment, our findings provide a basis for further research and options for clinical applications.

Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium

Epidemiological and experimental data point to involvement of oxygen derived radicals in the pathogenesis of gynecological disorders, as well as in cancer development. The objective of the present study was to examine changes in activities and levels of copper/zinc superoxide dismutase (CuZnSOD) and lipid hydroperoxides (LOOH) in blood and endometrial tissue of patients diagnosed with uterine myoma, endometrial polypus, hyperplasia simplex, hyperplasia complex and adenocarcinoma endometrii. The results of our study have shown decreased SOD activities and unchanged SOD protein level in blood of all examined patients in comparison to healthy subjects. Decrease of both SOD activity and level was found in endometrium of patients with hyperplasia simplex, hyperplasia complex and adenocarcinoma in comparison to women with polypus or myoma. LOOH level was elevated in both tissues of patients with hyperplasiaor adenocarcinoma in comparison to healthy subjects or patients with benign diagnosis. Our findings suggest that the decrease in SOD activity and level, as well as the increase in LOOH level, in patients with gynecological disorders, render these patients more susceptible to oxidative damage caused by reactive oxygen species (ROS). An imbalance in ROS formation and SOD level may be important in the pathogenesis and/or perpetuation of tissue damage in gynecological patients. Since evidence suggests that SOD may be a therapy target for cancer treatment, our findings provide a basis for further research and options for clinical applications.

Resultados epidemiológicos e experimentais apontam para o envolvimento dos radicais derivados do oxigênio na patogênese das moléstias ginecológicas, assim como no desenvolvimento do câncer. O objetivo do presente estudo foi o de examinar as alterações nas atividades e níveis de Cu/Zn superóxido dismutase (CuZnSOD) e hidroperóxidos lipídicos (LOOH)no sangue e tecido endometrial de pacientes diagnosticados com mioma uterino, pólipo endometrial, hiperplasia simplex, hiperplasia complex e adenocarcinoma do endométrio. Os resultados de nosso estudo mostraram atividades de SOD diminuídas e nível de SOD proteína inalterado no sangue de todos os pacientes examinados em comparação a indivíduos saudáveis. Diminuição de ambos, atividade de SOD e nível protéico, foram encontrados no endométrio de pacientes com hiperplasia simplex, hiperplasia complex e adenocarcinoma em comparação às mulheres com pólipos e/ou mioma. O nível de LOOH estava elevado em ambos os tecidos de pacientes com hyperplasia e adenocarcinoma em comparação a indivíduos saudáveis ou pacientes com diagnóstico benigno. Nossos resultados sugerem que um decréscimo na atividade e nível protéico de SOD, assim como um incremento no nível de LOOH, em pacientes com desordens ginecológicas, tornam esses pacientes mais susceptíveis ao dano oxidativo causado pelas espécies reativas de oxigênio (ROS). Um desequilíbrio na formação de ROS e no nível de SOD pode ser importante na patogênese e/ou perpetuação do dano tecidual em pacientes ginecológicos. Desde que existe evidência de que SOD pode ser um alvo para terapia de câncer, nossos resultados fornecem uma base para futura pesquisa e opções para aplicações clínicas.

[Inherited colour vision deficiencies--from Dalton to molecular genetics].

In recent years, great advances have been made in our understanding of the molecular basis of colour vision defects, as well as of the patterns of genetic variation in individuals with normal colour vision. Molecular genetic analyses have explained the diversity of types and degrees of severity in colour vision anomalies, their frequencies, pronounced individual variations in test results, etc. New techniques have even enabled the determination of John Dalton's real colour vision defect, 150 years after his death. Inherited colour vision deficiencies most often result from the mutations of genes that encode cone opsins. Cone opsin genes are linked to chromosomes 7 (the S or "blue" gene) and X (the L or "red" gene and the M or "green" gene). The L and M genes are located on the q arm of the X chromosome in a head-to-tail array, composed of 2 to 6 (typically 3) genes--a single L is followed by one or more M genes. Only the first two genes of the array are expressed and contribute to the colour vision phenotype. The high degree of homology (96%) between the L and M genes predisposes them to unequal recombination, leading to gene deletion or the formation of hybrid genes (comprising portions of both the L and M genes), explaining the majority of the common red-green colour vision deficiencies. The severity of any deficiency is influenced by the difference in spectral sensitivity between the opsins encoded by the first two genes of the array. A rare defect, S monochromacy, is caused either by the deletion of the regulatory region of the array or by mutations that inactivate the L and M genes. Most recent research concerns the molecular basis of complete achromatopsia, a rare disorder that involves the complete loss of all cone function. This is not caused by mutations in opsin genes, but in other genes that encode cone-specific proteins, e.g. channel proteins and transducin.