Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology

Searching for Speciation Genes: Molecular Evidence for Selection Associated with Colour Morphotypes in the Caribbean Reef Fish Genus Hypoplectrus

Closely related species that show clear phenotypic divergence, but without obvious geographic barriers, can provide opportunities to study how diversification can occur when opportunities for allopatric speciation are limited. We examined genetic divergence in the coral reef fish genus Hypoplectrus (family: Serranidae), which comprises of 10–14 morphotypes that are distinguished solely by their distinct colour patterns, but which show little genetic differentiation. Our goal was to detect loci that show clear disequilibrium between morphotypes and across geographical locations. We conducted Amplified Fragment Length Polymorphism molecular analysis to quantify genetic differentiation among, and selection between, morphotypes. Three loci were consistently divergent beyond neutral expectations in repeated pair-wise morphotype comparisons using two different methods. These loci provide the first evidence for genes that may be associated with colour morphotype in the genus Hypoplectrus

Aleitamento e hábitos orais deletérios em respiradores orais e nasais Breast-feeding and deleterious oral habits in mouth and nose breathers

OBJETIVO: A amamentação promove vários benefícios na criança, entre eles o favorecimento da respiração nasal. Neste estudo verificou-se a relação do padrão respiratório com o histórico de aleitamento e hábitos orais deletérios. FORMA DE ESTUDO: clínico com coorte transversal. MATERIAL E MÉTODO: A população foi constituída por 62 crianças, de 3 anos e 3 meses a 6 anos e 11 meses, as quais foram submetidas à avaliação otorrinolaringológica, para definição dos grupos respiradores nasais e orais e entrevista fonoaudiológica. A avaliação otorrinolaringológica constituiu-se dos seguintes exames: rinoscopia anterior, oroscopia e exame radiológico. Os pais das crianças foram questionados em relação à forma (natural e/ou artificial), e ao período de aleitamento, além da presença de hábitos orais deletérios (sucção e mordida). O teste Exato de Fisher foi utilizado para comparar os grupos em relação à presença ou ausência de hábitos e diferentes períodos de aleitamento. RESULTADOS: O período de aleitamento materno foi maior nos respiradores nasais concentrando-se no período de 3 a 6 meses de idade. Quanto ao uso de mamadeira, os resultados mostraram que a maioria das crianças de ambos os grupos utilizou-se deste tipo de aleitamento nos primeiros anos de vida, não apresentando diferença estatística entre os grupos (p=0.58). A presença de hábitos orais deletérios ocorreu de maneira marcante nos respiradores orais, evidenciando diferença estatisticamente significativa, entre os grupos, para os hábitos de sucção (p=0.004) e hábitos de mordida (p=0.0002). CONCLUSÃO: As crianças respiradoras orais apresentaram um menor período de aleitamento materno e um histórico de hábitos orais presentes comparadas às crianças respiradoras nasais.<br>AIM: Breast-feeding promotes several benefits in childhood, among them favoring the nasal breathing. In the present study, the relationship between breathing pattern and the history of breast-feeding and of deleterious oral habits was determined. STUDY DESIGN: clinical with transversal cohort. MATERIAL AND METHOD: The study population consisted of 62 children ranging in age from 3 years and 3 months to 6 years and 11 months who were submitted to otorhinolaryngologic evaluation to determine nasal and mouth breathers and to a speech language pathologic interview. The otorhinolaryngologic evaluation involved the following exams: anterior rhinoscopy, oroscopy and radiologic examination. The parents of the children were questioned about the form of feeding (natural and/or artificial), the duration of breast-feeding and the presence of deleterious oral habits (suction and biting). The Fisher exact test was used to compare groups regarding the presence and absence of habits and the different periods of breast-feeding. RESULTS: The breast-feeding period was longer among nasal breathers and was concentrated in the period between 3 and 6 months of age. Regarding the use of bottle, the results showed that most of the children in both groups used this type of feeding during the first years of life, with no significant difference between groups (p=0.58). There was a marked presence of deleterious oral habits among mouth breathers, with a statistically significant difference between groups regarding suction (p=0.004) and biting habits (p=0.0002). CONCLUSION: Mouth breathing children were breast-fed for a shorter period of time and had a history of deleterious oral habits compared to nose breathers

Loss of function effect of RET mutations causing Hirschsprung disease

15nononeWe have introduced three Hirschsprung (HSCR) mutations localized in the tyrosine kinase domain of RET into the RET/PTC2 chimaeric oncogene which is capable of transforming NIH3T3 mouse fibroblasts and of differentiating pC12 rat pheochromocytoma cells. The three HSCR mutations abolished the biological activity of RET/PTC2 in both cell types and significantly decreased its tyrosine phosphorylation. By contrast, a rare polymorphism in exon 18 does not alter the transforming capability of RET/PTC2 or its tyrosine phosphorylation. These data suggest a loss of function effect of HSCR mutations which might act through a dominant negative mechanism. Our model system is therefore capable of discriminating between causative HSCR mutations and rare polymorphisms in the tyrosine kinase domain of RET.nonePASINI, B; BORRELLO, M.G. ; GRECO, A.; BONGARZONE, I.; YIN, L.; MONDELLINI, P.; ALBERTI, L.; MIRANDA, C.; ARIGHI, E.; BOCCIARDI, R.; SERI, M.; BARONE, V. ; RADICE, M.T. ; ROMEO, G.; PIEROTTI, M.A.Pasini, B; Borrello, M. G.; Greco, A.; Bongarzone, I.; Yin, L.; Mondellini, P.; Alberti, L.; Miranda, C.; Arighi, E.; Bocciardi, R.; Seri, M.; Barone, V.; Radice, M. T.; Romeo, G.; Pierotti, M. A

Renaturing science : the role of childhoodnature in science for the anthropocene

This chapter proposes that there is a need to examine childhoodnature experiences and the way in which these might be influential in shaping an agenda for science and science education in the Anthropocene. A renaturing of science places a much greater emphasis on, and recognition of, the interdependency and relational nature of the natural world in which humans are inextricably embedded and suggests the need for the development of a strong ecological identity (Thomashow, Ecological identity: Becoming a reflective environmentalist. MIT Press, Cambridge, MA, 1996). This suggests that there is a need for increased availability of childhoodnature experiences and a focus on the quality of those experiences, as well as the need to explore further lifelong opportunities for developing innate biophilic (Wilson, Biophilia. Harvard University Press, Cambridge, MA, 1984) tendencies. The chapter examines the childhoodnature experiences of beginning undergraduate university students and how these influence their current relationship to the natural world. Literature suggests that the strength of a person’s nature relatedness can have an impact on the way they view the natural world and can, subsequently, influence the actions they take toward that natural world. This chapter describes a mixed-methods approach used to examine beginning university students’ childhoodnature experiences and how those experiences may have influenced their sense of nature connectedness. Data gathered indicates that there are statistically significant correlations between childhoodnature experiences and current sense of nature connectedness, although the qualitative data suggests that the form of those experiences may be of critical importance. Evidence from the study presented here suggests that exposure to childhoodnature, while necessary, is not sufficient in itself, and further research is required into the nature and quality of childhoodnature experiences. This concurs with previous studies, e.g., Vadala, Bixler, and James (J Environ Educ 39:3–18, 2007), which found that it was the particular qualities of the childhoodnature experience that appeared to play a significant part in shaping future interests, attitudes, and values