Gene structure, transcripts and calciotropic effects of the PTH family of peptides in Xenopus and chicken

<p>Abstract</p> <p>Background</p> <p>Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) belong to a family of endocrine factors that share a highly conserved N-terminal region (amino acids 1-34) and play key roles in calcium homeostasis, bone formation and skeletal development. Recently, PTH-like peptide (PTH-L) was identified in teleost fish raising questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation. This study investigated PTH family evolution in vertebrates with special emphasis on <it>Xenopus </it>and chicken.</p> <p>Results</p> <p>The PTH-L gene is present throughout the vertebrates with the exception of placental mammals. Gene structure of PTH and PTH-L seems to be conserved in vertebrates while PTHrP gene structure is divergent and has acquired new exons and alternative promoters. Splice variants of PTHrP and PTH-L are common in <it>Xenopus </it>and chicken and transcripts of the former have a widespread tissue distribution, although PTH-L is more restricted. PTH is widely expressed in fish tissue but from <it>Xenopus </it>to mammals becomes largely restricted to the parathyroid gland. The N-terminal (1-34) region of PTH, PTHrP and PTH-L in <it>Xenopus </it>and chicken share high sequence conservation and the capacity to modify calcium fluxes across epithelia suggesting a conserved role in calcium metabolism possibly via similar receptors.</p> <p>Conclusions</p> <p>The parathyroid hormone family contains 3 principal members, PTH, PTHrP and the recently identified PTH-L. In teleosts there are 5 genes which encode PTHrP (2), PTH (2) and PTH-L and in tetrapods there are 3 genes (PTHrP, PTH and PTH-L), the exception is placental mammals which have 2 genes and lack PTH-L. It is hypothesized that genes of the PTH family appeared at approximately the same time during the vertebrate radiation and evolved via gene duplication/deletion events. PTH-L was lost from the genome of eutherian mammals and PTH, which has a paracrine distribution in lower vertebrates, became the product of a specific endocrine tissue in Amphibia, the parathyroid gland. The PTHrP gene organisation diverged and became more complex in vertebrates and retained its widespread tissue distribution which is congruent with its paracrine nature.</p

Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states

<p>Abstract</p> <p>Background</p> <p>Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression.</p> <p>Methods</p> <p>To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR.</p> <p>Results</p> <p>Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes.</p> <p>Conclusion</p> <p>Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states.</p

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Atuação da cirurgia plástica no tratamento de feridas complexas

OBJETIVO: Relatar a atuação da Cirurgia Plástica no tratamento das feridas complexas em hospital terciário, analisando suas características, tipos de lesões e condutas adotadas, com ênfase no tratamento cirúrgico. MÉTODOS: Análise retrospectiva dos pacientes com feridas complexas atendidos pela Cirurgia Plástica em hospital terciário, através dos pedidos de consulta, em um período de cinco anos (2006 a 2010). A coleta dos dados foi obtida a partir de atendimentos realizados, avaliações seriadas e registros do prontuário médico. RESULTADOS: Foram atendidos 1927 pacientes (32 consultas/mês), com média de idade de 46,3 anos, predominando o sexo masculino (62%). As especialidades cirúrgicas solicitaram 1076 consultas (56%) e as clínicas, 851 (44%). A distribuição por tipo de ferida demonstrou predomínio das úlceras por pressão (635/33%), das feridas traumáticas (570/30%), cirúrgicas complicadas (305/16%) e necrotizantes (196/10%), sendo o restante representado por vasculite (83/4%), úlceras venosas (79/4%), diabéticas (41/2%) e pós-radiação (18/1%). O tratamento foi operatório em 1382 pacientes (72%) e não-operatório em 545 casos (28%). Nos pacientes operados, realizaram-se 3029 operações, predominando os desbridamentos (1988/65%) e enxertias de pele (619/21%) associadas ou não com a terapia por pressão negativa (vácuo), seguido pelos retalhos pediculados (237/8%), reimplantes digitais (81/3%), retalhos microcirúrgicos (66/2%) e outros procedimentos (38/1%). CONCLUSÃO: O cirurgião plástico demonstrou ter importante atuação no tratamento das feridas complexas por adotar o tratamento cirúrgico mais precocemente, colaborando para a efetiva resolução dos casos

A deficiência de vitamina A em crianças no Brasil e no mundo Vitamin A deficiency among children in Brazil and worldwide

O presente artigo expõe, com base em uma revisão de literatura dos últimos dez anos, aspectos relevantes da Deficiência de Vitamina A (DVA) em crianças no Brasil e no mundo. Apresenta a DVA no contexto da deficiência clínica e subclínica, com ênfase na caracterização desta como problema de saúde pública. A DVA foi diagnosticada em crianças de várias regiões do Brasil, principalmente no Sudeste e Nordeste; entretanto, não foram encontrados estudos relativos a sinais clínicos. Mundialmente, as maiores prevalências de DVA foram registradas em países da África como Mali, Etiópia e Nigéria, sendo que os sinais clínicos estiveram presentes, principalmente, em regiões da Ásia e África. Os estudos apontam a DVA como problema de saúde pública em crianças, principalmente nas regiões mais pobres do globo.<br>Based on a ten-year literature review, this paper describes important aspects of Vitamin A Deficiency (VAD) among children in Brazil and worldwide. It presents VAD within a clinical and sub-clinical deficiency context, emphasizing this as a public health issue. VAD has been diagnosed in children from several parts of Brazil, especially in the Southeast and Northeast. Worldwide, the highest VAD prevalence is found in parts of parts of Africa: Mali, Ethiopia and Nigeria, and clinical indications noted especially in parts of Asia and Africa. However, no studies of clinical indications were located. Studies point to VAD as a public health issue among children, particularly in the poorest parts of the world