Novel pathogenic mutations and skin biopsy analysis in Knobloch syndrome

Purpose: To facilitate future diagnosis of Knobloch syndrome (KS) and better understand its etiology, we sought to identify not yet described COL18A1 mutations in KS patients. In addition, we tested whether mutations in this gene lead to absence of the COL18A1 gene product and attempted to better characterize the functional effect of a previously reported missense mutation. Methods: Direct sequencing of COL18A1 exons was performed in KS patients from four unrelated pedigrees. We used immunofluorescent histochemistry in skin biopsies to evaluate the presence of type XVIII collagen in four KS patients carrying two already described mutations: c. 3277C>T, a nonsense mutation, and c. 3601G>A, a missense mutation. Furthermore, we determined the binding properties of the mutated endostatin domain p.A1381T (c.3601G>A) to extracellular matrix proteins using ELISA and surface plasmon resonance assays. Results: We identified four novel mutations in COL18A1, including a large deletion involving exon 41. Skin biopsies from KS patients revealed lack of type XVIII collagen in epithelial basement membranes and blood vessels. We also found a reduced affinity of p.A1381T endostatin to some extracellular matrix components. Conclusions: COL18A1 mutations involved in Knobloch syndrome have a distribution bias toward the coding exons of the C-terminal end. Large deletions must also be considered when point mutations are not identified in patients with characteristic KS phenotype. We report, for the first time, lack of type XVIII collagen in KS patients by immunofluorescent histochemistry in skin biopsy samples. As a final point, we suggest the employment of this technique as a preliminary and complementary test for diagnosis of KS in cases when mutation screening either does not detect mutations or reveals mutations of uncertain effect, such as the p.A1381T change.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) - CEPIDConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq

Healthy ageing, appetite, frailty and sarcopenia: a brief overview

In many societies the population is getting older, such that in some western countries it is expected that those over 80 years of age will make up 30% of the population (1-2). In the modern era, due to improved health and better medical support/treatment, many people may spend as many years retired as they did working. Unfortunately, as one ages, the burden of disease increases (2.9 million people in England have >1 long-term condition), longevity is compromised by disability; therefore the drive must be to add life to years rather than just years to life. When people live long, the media often asks “what is the success associated with longevity or successful (healthy) ageing?” Is it a success to live a long life, or is successful ageing the key? Healthy ageing, is defined as a state, where the effect of frailty, sarcopenia, disease and disability have been minimised. Farpour et al (3) discuss the effect that aging has on Iranian people, and Liang et al discuss the findings of a systematic review looking at traditional Chinese’ medicine and subhealth (4), which could be aligned to prefrailty. In 2015 the WHO defined Health as “a state of complex physical, mental and social well-being and not merely absence of disease” (5). Healthy ageing was also defined as “the process of developing and maintaining the functional ability that enables well-being in older age”. Rowe and Khan (1987) commented that to age successfully one must avoid disease, remain engaged with life and maintain a high level of physical and cognitive function (6). Healthy ageing is, therefore, a complex interplay between physical, cognitive and social factors, and perhaps is dependent on how we individually respond to the internal and external forces at play (table 1). The definition of what is normal and what is abnormal is fraught with difficulty; what is acceptable and what is not? There is a risk that where normative parameters (for younger adults) are exceeded there will be a medicalisation of “older age”! What ultimately matters is the preservation of functional ability, which the majority (75%) of very old people are able to do and live relatively independent lives (6). This paper will discuss the interdependency between healthy ageing, appetite, frailty and sarcopenia and their impact on functional ability

Ciências biológicas – uma forma de integrar e construir a prática experimental

Trabalho apresentado no 31º SEURS - Seminário de Extensão Universitária da Região Sul, realizado em Florianópolis, SC, no período de 04 a 07 de agosto de 2013 - Universidade Federal de Santa Catarina.Há muitos anos, o ensino médio das escolas públicas, vem sendo deixado de lado, enfrentando com isso uma série de dificuldades, dentre elas podemos citar a estrutura predial e laboratorial, que em muitos casos são precários. Podemos destacar ainda a falta de oportunidade/incentivo a qualificação dos professores e a precária (ou ausente) realização de práticas científicas com os estudantes. Partindo deste contexto, encontramos um ensino que na grande maioria dos casos é puramente teórico. Dessa forma nos propomos, por meio do presente projeto, realizar com alunos do ensino médio das escolas parceiras seminários, práticas em laboratório e oficinas didáticas em ciências biológicas; cursos de terapias integrativas e complementares e inserção de alunos interessados e selecionados em projetos de pesquisa nas áreas de ciências biológicas e saúde, os quais estão sendo realizados na unidade de saúde do município de uma das escolas parceiras. As parcerias foram firmadas no ano 2012 com duas escolas que já vinham participando do projeto em 2011 e 2012 e com uma nova escola que integrou o projeto em 2013. Até o momento realizamos algumas atividades práticas nos laboratórios da UFFS e estamos organizando os cursos de terapias integrativas para ministrar aos professores e alunos do 3º ano do ensino médio do município onde estão sendo realizados os projetos de pesquisa. Os seminários, oficinas de materiais didáticos e atividades laboratoriais versam sobre assuntos abordados nos três anos do ensino médio. As escolas vêm relatando que as atividades estão auxiliando de forma significativa o processo de aprendizagem dos alunos participantes

Mutations in collagen 18A1 (COL18A1) and their relevance to the human phenotype

Collagen XVIII, a proteoglycan, is a component of basement membranes (BMs). There are three distinct isoforms that differ only by their N-terminal, but with a specific pattern of tissue and developmental expression. Cleavage of its C-terminal produces endostatin, an inhibitor of angiogenesis. In its N-terminal, there is a frizzled motif which seems to be involved in Wnt signaling. Mutations in this gene cause Knobloch syndrome KS), an autosomal recessive disorder characterized by vitreoretinal and macular degeneration and occipital encephalocele. This review discusses the effect of both rare and polymorphic alleles in the human phenotype, showing that deficiency of one of the collagen XVIII isoforms is sufficient to cause KS and that null alleles causing deficiency of all collagen XVIII isoforms are associated with a more severe ocular defect. This review besides illustrating the functional importance of collagen XVIII in eye development and its structure maintenance throughout life, it also shows its role in other tissues and organs, such as nervous system and kidney

O ENSINO DE CIÊNCIAS BIOLÓGICAS - UMA EXPERIÊNCIA TEÓRICO-PRÁTICA COM ALUNOS DO ENSINO MÉDIO DE ESCOLAS PÚBLICAS

Resumo: Este trabalho foi uma iniciativa do projeto “Ciências Biológicas – Uma Forma de Integrar e Construir a Prática Experimental”, cuja ação de destaque foi o incentivo ao ensino de Ciências Biológicas para alunos de ensino médio de dois municípios. Foram oferecidas aulas teóricas e práticas em laboratórios da Universidade Federal da Fronteira Sul (UFFS), promovendo o contato de alunos e professores de escolas públicas com a universidade. Neste contexto, foi possível aproximá-los de atividades, materiais e equipamentos de prática científica e de ensino nas áreas de Ciências Biológicas, visando melhorias das condições de aprendizagem e estimulando os jovens dessas escolas para a participação no meio acadêmico-científico, aumentando a interação universidade/escola pública. Foram atendidas 15 turmas, totalizando cerca de 320 estudantes, que presenciaram as aulas de “Microscopia, células e tecidos”, “Tipagem sanguínea” e “Biodecomposição de alimentos orgânicos”. Esse trabalho possibilitou que os alunos tivessem contato prévio com o mundo das ciências e os incentivou para ingressar na universidade. Já os professores que acompanharam os alunos se sentiram instigados a manter a criatividade em sala de aula. Para os acadêmicos envolvidos, o projeto possibilitou o crescimento pessoal, instigando os mesmos a desenvolver aptidões, além do que lhes é ensinado em sala de aula. Palavras-chave: Práticas laboratoriais, ensino-aprendizagem, escola pública, extensão universitária.   The teaching of Biological Sciences - a theoretical and practical experience with students of high public schools Abstract: This article promotes the project ‘Ciências Biológicas – Uma Forma de Integrar e Construir a Prática Experimental’ (Biological Sciences – a way to integrate and to build experimental practices).  This initiative encouraged the teaching of biological sciences to high school students of two municipalities. Theoretical and practical classes were offered in the university labs of Universidade Federal Fronteira Sul –UFFS (Chapecó, Santa Catarina State, Brazil) in order to promote the contact of students and teachers of public schools with the university. In this context, it was possible to put the students in contact with procedures, equipments scientific and teaching practices in the areas of Biological Sciences. These activities aimed at improving learning and stimulating the students from the schools in which were part of the academic and scientific community, and as a result, to promote the interaction between university and public schools. Fifteen student groups took part in the project, which totaled around 320 students who had lessons on microscopy, cells and tissues, blood typing and biological decomposition of organic food. This project encouraged students that had a previous contact with the world of science to enter university. In addition, the teachers who accompanied the students were encouraged to continue being creative in their classes. For the undergraduate students involved, the project enabled personal growth and encouraged them to develop skills beyond what they were taught in the classroom. Key-words: Laboratory Practices, Teaching and Learning, Public School, University Extension.   La enseñanza de Ciencias Biológicas - una experiencia teórica y práctica con los estudiantes de la escuela secundaria en escuelas públicas Resumen: En este artículo, se hace un relato de un trabajo que tuvo una iniciativa del proyecto ‘Ciências Biológicas – Uma Forma de Integrar e Construir a Prática Experimental’ (Ciencias Biológicas – Una Forma de Integrar y Construir la Práctica Experimental), cuya acción principal fue el incentivo a la enseñanza de Ciencias Biológicas para alumnos de enseñanza media de dos municipios. Se les ofreció clases teóricas y prácticas en los laboratorios de la Universidade Federal da Fronteira Sul – UFFS (Santa Catarina, sur de Brasil) promoviendo el contacto de alumnos y profesores de escuelas públicas con la universidad. En este espacio, fue posible aproximarlos a actividades, materiales y equipamientos de la práctica científica y de la enseñanza en las áreas de Ciencias Biológicas, buscando mejorías en las condiciones de aprendizaje y estimular los jóvenes de esas escuelas a la participación en el medio académico-científico, aumentando la interacción universidad/escuela pública. Han sido atendidos 15 grupos y cerca de 320 estudiantes, que fueron testigos de las lecciones de “Microscopía, células y tejidos”, “Tipo sanguíneo”, y “Biodescomposición de alimentos orgánicos”. Ese trabajo ha posibilitado que los alumnos tuvieran un contacto previo con el mundo de las ciencias y los ha incentivado a ingresar a la universidad. Por otro lado, los docentes que han acompañado a los alumnos se han sentido instigados a mantener la creatividad en las clases. Para los académicos involucrados, el proyecto ha posibilitado el crecimiento personal, instigándolos a crear aptitudes, más allá de lo que les es enseñado en el salón de clase. Palabras-clave: Extensión Universitaria, Popularización de la Ciencia, Escuela Secundaria, Enseñanza Científica

O ENSINO DE CIÊNCIAS BIOLÓGICAS - UMA EXPERIÊNCIA TEÓRICO-PRÁTICA COM ALUNOS DO ENSINO MÉDIO DE ESCOLAS PÚBLICAS

Resumo: Este trabalho foi uma iniciativa do projeto “Ciências Biológicas – Uma Forma de Integrar e Construir a Prática Experimental”, cuja ação de destaque foi o incentivo ao ensino de Ciências Biológicas para alunos de ensino médio de dois municípios. Foram oferecidas aulas teóricas e práticas em laboratórios da Universidade Federal da Fronteira Sul (UFFS), promovendo o contato de alunos e professores de escolas públicas com a universidade. Neste contexto, foi possível aproximá-los de atividades, materiais e equipamentos de prática científica e de ensino nas áreas de Ciências Biológicas, visando melhorias das condições de aprendizagem e estimulando os jovens dessas escolas para a participação no meio acadêmico-científico, aumentando a interação universidade/escola pública. Foram atendidas 15 turmas, totalizando cerca de 320 estudantes, que presenciaram as aulas de “Microscopia, células e tecidos”, “Tipagem sanguínea” e “Biodecomposição de alimentos orgânicos”. Esse trabalho possibilitou que os alunos tivessem contato prévio com o mundo das ciências e os incentivou para ingressar na universidade. Já os professores que acompanharam os alunos se sentiram instigados a manter a criatividade em sala de aula. Para os acadêmicos envolvidos, o projeto possibilitou o crescimento pessoal, instigando os mesmos a desenvolver aptidões, além do que lhes é ensinado em sala de aula. Palavras-chave: Práticas laboratoriais, ensino-aprendizagem, escola pública, extensão universitária.   The teaching of Biological Sciences - a theoretical and practical experience with students of high public schools Abstract: This article promotes the project ‘Ciências Biológicas – Uma Forma de Integrar e Construir a Prática Experimental’ (Biological Sciences – a way to integrate and to build experimental practices).  This initiative encouraged the teaching of biological sciences to high school students of two municipalities. Theoretical and practical classes were offered in the university labs of Universidade Federal Fronteira Sul –UFFS (Chapecó, Santa Catarina State, Brazil) in order to promote the contact of students and teachers of public schools with the university. In this context, it was possible to put the students in contact with procedures, equipments scientific and teaching practices in the areas of Biological Sciences. These activities aimed at improving learning and stimulating the students from the schools in which were part of the academic and scientific community, and as a result, to promote the interaction between university and public schools. Fifteen student groups took part in the project, which totaled around 320 students who had lessons on microscopy, cells and tissues, blood typing and biological decomposition of organic food. This project encouraged students that had a previous contact with the world of science to enter university. In addition, the teachers who accompanied the students were encouraged to continue being creative in their classes. For the undergraduate students involved, the project enabled personal growth and encouraged them to develop skills beyond what they were taught in the classroom. Key-words: Laboratory Practices, Teaching and Learning, Public School, University Extension.   La enseñanza de Ciencias Biológicas - una experiencia teórica y práctica con los estudiantes de la escuela secundaria en escuelas públicas Resumen: En este artículo, se hace un relato de un trabajo que tuvo una iniciativa del proyecto ‘Ciências Biológicas – Uma Forma de Integrar e Construir a Prática Experimental’ (Ciencias Biológicas – Una Forma de Integrar y Construir la Práctica Experimental), cuya acción principal fue el incentivo a la enseñanza de Ciencias Biológicas para alumnos de enseñanza media de dos municipios. Se les ofreció clases teóricas y prácticas en los laboratorios de la Universidade Federal da Fronteira Sul – UFFS (Santa Catarina, sur de Brasil) promoviendo el contacto de alumnos y profesores de escuelas públicas con la universidad. En este espacio, fue posible aproximarlos a actividades, materiales y equipamientos de la práctica científica y de la enseñanza en las áreas de Ciencias Biológicas, buscando mejorías en las condiciones de aprendizaje y estimular los jóvenes de esas escuelas a la participación en el medio académico-científico, aumentando la interacción universidad/escuela pública. Han sido atendidos 15 grupos y cerca de 320 estudiantes, que fueron testigos de las lecciones de “Microscopía, células y tejidos”, “Tipo sanguíneo”, y “Biodescomposición de alimentos orgánicos”. Ese trabajo ha posibilitado que los alumnos tuvieran un contacto previo con el mundo de las ciencias y los ha incentivado a ingresar a la universidad. Por otro lado, los docentes que han acompañado a los alumnos se han sentido instigados a mantener la creatividad en las clases. Para los académicos involucrados, el proyecto ha posibilitado el crecimiento personal, instigándolos a crear aptitudes, más allá de lo que les es enseñado en el salón de clase. Palabras-clave: Extensión Universitaria, Popularización de la Ciencia, Escuela Secundaria, Enseñanza Científica

Astrocyte morphology after ischemic and hemorrhagic experimental stroke has no influence on the different recovery patterns

Stroke, broadly subdivided into ischemic and hemorrhagic subtypes, is a serious health-care problem worldwide. Previous studies have suggested ischemic and hemorrhagic stroke could present different functional recovery patterns. However, little attention has been given to this neurobiological finding. Coincidently, astrocyte morphology could be related to improved sensorimotor recovery after skilled reaching training and modulated by physical exercise and environmental enrichment. Therefore, it is possible that astrocyte morphology might be linked to differential recovery patterns between ischemic and hemorrhagic stroke. Thus, we decided to compare long-term GFAP-positive astrocyte morphology after ischemic (IS, n = 5), hemorrhagic (HS, n = 5) and sham (S, n = 5) stroke groups (induced by endothelin-1, collagenase type IV-S and salina, respectively). Our results showed ischemic and hemorrhagic stroke subtypes induced similar long-term GFAP-positive astrocyte plasticity (P > 0.05) for all evaluated measures (regional and cellular optical density; astrocytic primary processes ramification and length; density of GFAP positive astrocytes) in perilesional sensorimotor cortex and striatum. These interesting negative results discourage similar studies focused on long-term plasticity of GFAP-positive astrocyte morphology and recovery comparison of stroke subtypes