O lugar e a especificidade da educação na filosofia prática de Kant

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Electrical and mechanical effects of hyoscine butylbromide on the human stomach: a non-invasive approach

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Acheiropodia is caused by a genomic deletion in C7orf2, the human orthologue of the Lmbr1 gene

Acheiropodia is an autosomal recessive developmental disorder presenting with bilateral congenital amputations of the upper and lower extremities and aplasia of the hands and feet. This severely handicapping condition appears to affect only the extremities, with no other systemic manifestations reported. Recently, a locus for acheiropodia was mapped on chromosome 7q36. Herein we report the narrowing of the critical region for the acheiropodia gene and the subsequent identification of a common mutation in C7orf2-the human orthologue of the mouse Lmbr1 gene-that is responsible for the disease. Analysis of five families with acheiropodia, by means of 15 polymorphic markers, narrowed the critical region to 1.3 cM, on the basis of identity by descent, and to <0.5 Mb, on the basis of physical mapping. Analysis of C7orf2, the human orthologue of the mouse Lmbr1 gene, identified a deletion in all five families, thus identifying a common acheiropodia mutation. The deletion was identified at both the genomic-DNA and mRNA level. It leads to the production of a C7orf2 transcript lacking exon 4 and introduces a premature stop codon downstream of exon 3. Given the nature of the acheiropodia phenotype, it appears likely that the Lmbr1 gene plays an important role in limb development.

Characterization and oxygen binding properties of des-Arg human hemoglobin

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags

Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two million expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define approximate to23,500 genes, of which only approximate to1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes reveals that <1% do not have corresponding ESTs, indicating that the representation of genes associated with commonly studied tumors is high. The careful recording of the origin of all ESTs we have produced has enabled detailed definition of where the genes they represent are expressed in the human body. More than 100,000 ESTs are available for seven tissues, indicating a surprising variability of gene usage that has led to the discovery of a significant number of genes with restricted expression, and that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous germline variants (although the one-pass nature of the data necessitates careful validation) and many alternatively spliced transcripts. Although widely exploited by the scientific community, vindicating our totally open source policy, the EST data generated still provide extensive information that remains to be systematically explored, and that may further facilitate progress toward both the understanding and treatment of human cancers.

A microscopic survey of the human temporomandibular joint disc

The articular disc of the temporomandibular joint was studied in a foetuses and children group (GI), a dentate group of adults (GII) and an edentulous, elderly group of humans (GIII) by light microscopy. The main, constituent bundles of type I collagen fibres are stratified and are orientated sagittally, transversely and obliquely in the middle portion of the disc. In the thick, posterior portion, transverse bundles constitute the main feature. In the anterior portion of the disc, the fibres are sagittally and obliquely orientated. Type III. collagen fibres, intermingled with type I collagen fibres are present in all groups. The disc is cellular in nature in foetuses and children becoming more fibrous with age. Chondroid cells are observed in all portions of the discs in groups GII and GIII. Elastic fibres are numerous in GI discs and decrease in number in the disc with age. These fibres lie parallel to the collagen fibres in all three portions of the three groups.

Evaluation of Paracoccidioides brasiliensis exoantigen in the detection of delayed dermal hypersensitivity in experimental and human paracoccidioidomycosis

The exoantigen of Paracoccidioides brasiliensis standardized by Camargo et al. [1] (AgR) was used to evaluate the in vivo and in vitro cell immune response of experimental animals and of patients with paracoccidioidomycosis (PBM). Fava Netto antigen (AgF) was tested in parallel as a control antigen. The study was conducted with mice and guinea pigs infected with P. brasiliensis or immunized with its fungal antigens, on patients with PBM and on their respective control groups. The cell immune response was analysed by skin tests, and by the macrophage and leucocyte migration inhibition tests (MMIT and LMIT) in the animals and in the patients, respectively. The skin test with AgR as paracoccidioidin was positive in infected or immunized mice and guinea pigs and negative in control animals. The skin tests with AgR (24 h) showed 96.7% positivity in patients with PBM and were negative in control individuals. Histopathological study of the in vivo tests in the different experimental models was consistent with a delayed hypersensitivity response (DHR). Immunohistochemical study of the skin tests of PBM patients demonstrated a predominance of T lymphocytes, confirming the nature of a DHR to the fungal antigens. The in vitro cell immune response showed variable results for the various experimental models, i.e. significant rates of MMIT in immunized mice, a tendency to positivity in infected guinea pigs, and the absence of migration inhibition in PBM patients. Taken together, the data indicate that the AgR is efficient as paracoccidioidin in the evaluation of DHR in PBM, with an optimum time of reading the test of 24 h.

Morphological aspects of the mid-palatal suture in the human foetus: A light and scanning electron microscopy study

Morphological features of the mid-palatal suture were studied in human foetuses from 4 to 9 months of intra-uterine life. The foetuses were divided into three age groups, GI (16-23 weeks), GII (24-31 weeks) and GIII (32-39 weeks). The mid-palatal suture in GI foetuses is rectilineal in form with a wide space between the palatal processes of the maxilla. The suture has a sinuous nature in GII and GIII foetuses due to growth of the bone processes crossing the mid-line. A wide zone of cellular proliferation observed in GI narrows in GII and GIII foetuses. The imbricating nature of the suture in GII and GIII is caused by bone growth adjacent to the mid-palatal suture. Sharpey's fibres, emerging from the bone processes, run to the median region of the mid-palatal suture and are observed from GI foetuses onwards. The collagen fibres of the mid-palatal suture are orientated transversely under the oral epithelium and exhibit a regular meshwork with a predominance of sagittal fibres in the median region of the suture. These fibres are orientated transversely and obliquely at the junction with the nasal septum.

Pro- and anti-inflammatory cytokines produced by human monocytes challenged in vitro with Paracoccidioides brasiliensis

Monocytes and macrophages play a central role in innate and adaptive immune response against systemic fungal infections. Imbalances in suppressor or stimulatory cytokine secretion caused by these cells may influence disease development, microorganism death, and the nature of the adaptive immune response. This study analyzed the monocyte cytokine profiles of healthy individuals challenged with high and low virulent strains of P. brasiliensis and mRNA cytokine expression kinetics by reverse transcription polymerase chain reaction (RT-PCR). Peripheral blood monocytes from healthy volunteers were cultured in vitro with and without virulent (Pb18) or low virulence (Pb265) strains from P. brasiliensis viable yeast cells. Interleukin-1 beta (IL-1β), IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta (TGF-β1) were measured in culture supernatants by enzyme immunoassay (ELISA), and mRNA cytokine expression was determined by RT-PCR at 0, 4, 8, 12, 18 and 48 hr. Both P. brasiliensis strains induced monocyte production of IL-1β, IL-6, IL-10 and TNF-α. Pb18 induced higher levels of IL-1β, IL-6, and IL-10 than Pb265. IL-8 and TGF-β1 levels were not significantly different from those cultured without stimulus. The mRNA cytokine expression was similar to supernatant cytokines measured by ELISA. In vitro monocyte challenge with virulent P. brasiliensis strain induces earlier and higher levels of pro- and anti-inflammatory cytokines than low virulence strain.

Exploring the multifactorial nature of autism through computational systems biology: Calcium and the Rho GTPase RAC1 under the spotlight

Autism is a neurodevelopmental disorder characterized by impaired social interaction and communication accompanied with repetitive behavioral patterns and unusual stereotyped interests. Autism is considered a highly heterogeneous disorder with diverse putative causes and associated factors giving rise to variable ranges of symptomatology. Incidence seems to be increasing with time, while the underlying pathophysiological mechanisms remain virtually uncharacterized (or unknown). By systematic review of the literature and a systems biology approach, our aims were to examine the multifactorial nature of autism with its broad range of severity, to ascertain the predominant biological processes, cellular components, and molecular functions integral to the disorder, and finally, to elucidate the most central contributions (genetic and/or environmental) in silico. With this goal, we developed an integrative network model for gene-environment interactions (GENVI model) where calcium (Ca2+) was shown to be its most relevant node. Moreover, considering the present data from our systems biology approach together with the results from the differential gene expression analysis of cerebellar samples from autistic patients, we believe that RAC1, in particular, and the RHO family of GTPases, in general, could play a critical role in the neuropathological events associated with autism. © 2013 Springer Science+Business Media New York.

Human dental enamel and dentin structural effects after Er:yag laser irradiation

Ideally projected to be applied on soft tissues, infrared lasers were improved by restorative dentistry to be used in hard dental tissues cavity preparations-namely enamel and dentin. This paper evidentiates the relevant aspects of infrared Erbium laser's action mechanism and its effects, and characterizes the different effects deriving from the laser's beams emission. The criteria for use and selection of optimal parameters for the correct application of laser systems and infuence of supporting factors on the process, such as water amount and its presence in the ablation process, protection exerted by the plasma shielding and structural factors, which are indispensable in dental tissues cavity preparation related to restorative technique, are subordinated to optical modifcations caused by the interaction of the energy dissipated by these laser light emission systems in the targeted tissue substrate. Clinical relevance: Differences in the action of infrared Erbium laser system in regard to the nature of the ablation process and variations on the morphological aspects observed in the super-fcial structure of the target tissue irradiated, may be correlated to the structural optical modifcations of the substrate produced by an interaction of the energy propagated by laser systems.

Khoisan hunter-gatherers have been the largest population throughout most of modern-human demographic history

The Khoisan people from Southern Africa maintained ancient lifestyles as hunter-gatherers or pastoralists up to modern times, though little else is known about their early history. Here we infer early demographic histories of modern humans using whole-genome sequences of five Khoisan individuals and one Bantu speaker. Comparison with a 420 K SNP data set from worldwide individuals demonstrates that two of the Khoisan genomes from the Ju/'hoansi population contain exclusive Khoisan ancestry. Coalescent analysis shows that the Khoisan and their ancestors have been the largest populations since their split with the non-Khoisan population similar to 100-150 kyr ago. In contrast, the ancestors of the non-Khoisan groups, including Bantu-speakers and non-Africans, experienced population declines after the split and lost more than half of their genetic diversity. Paleoclimate records indicate that the precipitation in southern Africa increased similar to 80-100 kyr ago while west-central Africa became drier. We hypothesize that these climate differences might be related to the divergent-ancient histories among human populations.