AVALIAÇÃO DA COMPRESSÃO DA IMAGEM DIGITAL DA TELERRADIOGRAFIA LATERAL NA REPRODUTIBILIDADE DA MARCAÇÃO DE PONTOS CEFALOMÉTRICOS

A imagem digital adquirida pelo sistema da placa de fósforo foto ativada é visualizada no monitor do computador em um formato denominado DICOM. Este formato ocupa muito espaço para armazenamento, o que dificulta o arquivamento e transmissão da imagem pela Internet. O objetivo deste estudo foi avaliar a influência da compressão JPEG, nos Fatores de Qualidade 100, 80 e 60 na reprodutibilidade da marcação de pontos cefalométricos em imagens de telerradiografias em norma lateral comparadas com o formato DICOM. A amostra consistiu de 120 imagens de telerradiografias em norma lateral obtidas a partir de 30 indivíduos, dos quais se obteve uma radiografia digital no formato DICOM. Essas imagens foram convertidas para o formato JPEG. Após o cegamento e randomização da amostra, três Ortodontistas calibrados marcaram a localização de 12 pontos cefalométricos em cada imagem utilizando o sistema de coordenadas X e Y. Esse procedimento foi repetido após 1 mês. A reprodutibilidade intra e inter observador foi calculada usando o teste de correlação intraclasse. Para comparação entre os grupos de compressão e DICOM na reprodutibilidade de marcação dos pontos utilizou se a Análise de Variância (ANOVA) a um critério para medidas repetidas. Os resultados mostraram que as marcações dos pontos cefalométricos foram bastante reprodutíveis, exceto para o ponto Órbita na coordenada X. Os diferentes formatos de arquivo mostraram estatisticamente iguais para cada ponto e eixo aferido. As compressões JPEG estudadas das imagens de telerradiografias em norma lateral não tiveram efeito na reprodutibilidade da marcação dos pontos cefalométricos testados.

AVALIAÇÃO DA REPRODUTIBILIDADE DE PONTOS CEFALOMÉTRICOS NAS TELERRADIOGRAFIAS DIGITAIS EM NORMA LATERAL NOS FORMATOS DICOM, TIFF E JPEG

A imagem radiográfica digital adquirida pelo sistema de placa de fósforo foto ativada é normalmente visualizada no monitor do computador no formato DICOM, caracterizado pela alta resolução das imagens. Como este formato ocupa muito espaço para armazenamento, as imagens digitais são submetidas a uma compressão, que otimiza a capacidade de espaço dos computadores e reduz o tempo de transmissão pela Internet. O objetivo desse estudo foi avaliar a influência da compressão TIFF e JPEG na reprodutibilidade intra e interexaminador da marcação de pontos cefalométricos em imagens de telerradiografias em norma lateral comparadas com o formato DICOM. A amostra consistiu de 90 imagens de telerradiografias obtidas a partir de 30 indivíduos, dos quais se obteve uma radiografia digital exibida no formato DICOM. Estas imagens foram convertidas para os formatos JPEG, com Fator de Qualidade 80 e TIFF. Após o cegamento e randomização da amostra, três ortodontistas calibrados marcaram a localização de 15 pontos cefalométricos em cada imagem utilizando o sistema de coordenadas x e y. Os resultados mostraram que as marcações dos pontos cefalométricos apresentaram concordância de reprodutibilidade tanto intra como interexaminador, exceto para os pontos Go, Po, Or, B e Pog . Os diferentes formatos de arquivo mostraram resultados estatisticamente semelhantes para cada ponto e eixo aferido. As compressões JPEG e TIFF estudadas não tiveram efeito, em imagens de telerradiografias em norma lateral, na reprodutibilidade intra e interexaminadores da marcação dos pontos cefalométricos testados.(AU)

AVALIAÇÃO DA REPRODUTIBILIDADE DE PONTOS CEFALOMÉTRICOS NAS TELERRADIOGRAFIAS DIGITAIS EM NORMA LATERAL NOS FORMATOS DICOM, TIFF E JPEG

A imagem radiográfica digital adquirida pelo sistema de placa de fósforo foto ativada é normalmente visualizada no monitor do computador no formato DICOM, caracterizado pela alta resolução das imagens. Como este formato ocupa muito espaço para armazenamento, as imagens digitais são submetidas a uma compressão, que otimiza a capacidade de espaço dos computadores e reduz o tempo de transmissão pela Internet. O objetivo desse estudo foi avaliar a influência da compressão TIFF e JPEG na reprodutibilidade intra e interexaminador da marcação de pontos cefalométricos em imagens de telerradiografias em norma lateral comparadas com o formato DICOM. A amostra consistiu de 90 imagens de telerradiografias obtidas a partir de 30 indivíduos, dos quais se obteve uma radiografia digital exibida no formato DICOM. Estas imagens foram convertidas para os formatos JPEG, com Fator de Qualidade 80 e TIFF. Após o cegamento e randomização da amostra, três ortodontistas calibrados marcaram a localização de 15 pontos cefalométricos em cada imagem utilizando o sistema de coordenadas x e y. Os resultados mostraram que as marcações dos pontos cefalométricos apresentaram concordância de reprodutibilidade tanto intra como interexaminador, exceto para os pontos Go, Po, Or, B e Pog . Os diferentes formatos de arquivo mostraram resultados estatisticamente semelhantes para cada ponto e eixo aferido. As compressões JPEG e TIFF estudadas não tiveram efeito, em imagens de telerradiografias em norma lateral, na reprodutibilidade intra e interexaminadores da marcação dos pontos cefalométricos testados.(AU)

Reexamination of the mechanism of hydroxyl radical adducts formed from the reaction between familial amyotrophic lateral sclerosis-associated Cu,Zn superoxide dismutase mutants and H2O2

Amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of motor neurons in the spinal cord and motor cortex. Mutations to Cu,Zn superoxide dismutase (SOD) linked with familial ALS are reported to increase hydroxyl radical adduct formation from hydrogen peroxide as measured by spin trapping with 5,5′-dimethyl-1-pyrrolline N-oxide (DMPO). In the present study, we have used oxygen-17-enriched water and H2O2 to reinvestigate the mechanism of DMPO/⋅OH formation from the SOD and SOD mutants. The relative ratios of DMPO/⋅17OH and DMPO/⋅16OH formed in the Fenton reaction were 90% and 10%, respectively, reflecting the ratios of H217O2 to H216O2. The reaction of the WT SOD with H217O2 in bicarbonate/CO2 buffer yielded 63% DMPO/⋅17OH and 37% DMPO/⋅16OH. Similar results were obtained from the reaction between familial ALS SOD mutants and H217O2: DMPO/⋅17OH (64%); DMPO/⋅16OH (36%) from A4V and DMPO/⋅17OH (62%); and DMPO/⋅16OH (38%) from G93A. These results were confirmed further by using 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide spin trap, a phosphorylated analog of DMPO. Contrary to earlier reports, the present results indicate that a significant fraction of DMPO/⋅OH formed during the reaction of SOD and familial ALS SOD mutants with H2O2 is derived from the incorporation of oxygen from water due to oxidation of DMPO to DMPO/⋅OH presumably via DMPO radical cation. No differences were detected between WT and mutant SODs, neither in the concentration of DMPO/⋅OH or DEPMPO/⋅OH formed nor in the relative incorporation of oxygen from H2O2 or water.

Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex

The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.

Lateral magma flow in mafic sill complexes

We benefitted from discussions with many Earth scientists in different disciplines over the years; we particularly thank Ken Thomson, Donny Hutton, Brian O’Driscoll, Mike Petronis, Ken McDermott, Derek Keir, Ben van Wyk de Vries, and Davie Brown for their insights. We thank Schlumberger for software and data provision, and Department of Communications, Energy, and Natural Resources (Petroleum Affairs Division) in Ireland, Geoscience Australia, and PGS (Petroleum Geo-Services) for provision of seismic data. This work was completed as part of Magee’s Junior Research Fellowship funded by Imperial College London. Muirhead acknowledges support from Fulbright New Zealand and the Ministry of Science and Innovation. We thank Shan de Silva for his editorial handling of the manuscript and Tyrone Rooney, Agust Gudmundsson, and Mattia Pistone for the time and effort they put in to their constructive reviews

Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant

Mutations in superoxide dismutase 1 (SOD1; EC 1.15.1.1) are responsible for a proportion of familial amyotrophic lateral sclerosis (ALS) through acquisition of an as-yet-unidentified toxic property or properties. Two proposed possibilities are that toxicity may arise from imperfectly folded mutant SOD1 catalyzing the nitration of tyrosines [Beckman, J. S., Carson, M., Smith, C. D. & Koppenol, W. H. (1993) Nature (London) 364, 584] through use of peroxynitrite or from peroxidation arising from elevated production of hydroxyl radicals through use of hydrogen peroxide as a substrate [Wiedau-Pazos, M., Goto, J. J., Rabizadeh, S., Gralla, E. D., Roe, J. A., Valentine, J. S. & Bredesen, D. E. (1996) Science 271, 515–518]. To test these possibilities, levels of nitrotyrosine and markers for hydroxyl radical formation were measured in two lines of transgenic mice that develop progressive motor neuron disease from expressing human familial ALS-linked SOD1 mutation G37R. Relative to normal mice or mice expressing high levels of wild-type human SOD1, 3-nitrotyrosine levels were elevated by 2- to 3-fold in spinal cords coincident with the earliest pathological abnormalities and remained elevated in spinal cord throughout progression of disease. However, no increases in protein-bound nitrotyrosine were found during any stage of SOD1-mutant-mediated disease in mice or at end stage of sporadic or SOD1-mediated familial human ALS. When salicylate trapping of hydroxyl radicals and measurement of levels of malondialdehyde were used, there was no evidence throughout disease progression in mice for enhanced production of hydroxyl radicals or lipid peroxidation, respectively. The presence of elevated nitrotyrosine levels beginning at the earliest stages of cellular pathology and continuing throughout progression of disease demonstrates that tyrosine nitration is one in vivo aberrant property of this ALS-linked SOD1 mutant.

Conservation of the Drosophila lateral inhibition pathway in human lung cancer: A hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression

The achaete-scute genes encode essential transcription factors in normal Drosophila and vertebrate nervous system development. Human achaete-scute homolog-1 (hASH1) is constitutively expressed in a human lung cancer with neuroendocrine (NE) features, small cell lung cancer (SCLC), and is essential for development of the normal pulmonary NE cells that most resemble this neoplasm. Mechanisms regulating achaete-scute homolog expression outside of Drosophila are presently unclear, either in the context of the developing nervous system or in normal or neoplastic cells with NE features. We now provide evidence that the protein hairy-enhancer-of-split-1 (HES-1) acts in a similar manner as its Drosophila homolog, hairy, to transcriptionally repress achaete-scute expression. HES-1 protein is detected at abundant levels in most non-NE human lung cancer cell lines which lack hASH1 but is virtually absent in hASH1-expressing lung cancer cells. Moreover, induction of HES-1 in a SCLC cell line down-regulates endogenous hASH1 gene expression. The repressive effect of HES-1 is directly mediated by binding of the protein to a class C site in the hASH1 promoter. Thus, a key part of the process that determines neural fate in Drosophila is conserved in human lung cancer cells. Furthermore, modulation of this pathway may underlie the constitutive hASH1 expression seen in NE tumors such as SCLC, the most virulent human lung cancer.

Postnatal mouse subventricular zone neuronal precursors can migrate and differentiate within multiple levels of the developing neuraxis

The mammalian subventricular zone (SVZ) of the lateral wall of the forebrain ventricle retains a population of proliferating neuronal precursors throughout life. Neuronal precursors born in the postnatal and adult SVZ migrate to the olfactory bulb where they differentiate into interneurons. Here we tested the potential of mouse postnatal SVZ precursors in the environment of the embryonic brain: (i) a ubiquitous genetic marker, (ii) a neuron-specific transgene, and (iii) a lipophilic-dye were used to follow the fate of postnatal day 5–10 SVZ cells grafted into embryonic mouse brain ventricles at day 15 of gestation. Graft-derived cells were found at multiple levels of the neuraxis, including septum, thalamus, hypothalamus, and in large numbers in the midbrain inferior colliculus. We observed no integration into the cortex. Neuronal differentiation of graft derived cells was demonstrated by double-staining with neuron-specific β-tubulin antibodies, expression of the neuron-specific transgene, and the dendritic arbors revealed by the lipophilic dye. We conclude that postnatal SVZ cells can migrate through and differentiate into neurons within multiple embryonic brain regions other than the olfactory bulb.

Retinotopic mapping of lateral geniculate nucleus in humans using functional magnetic resonance imaging

Subcortical nuclei in the thalamus, which play an important role in many functions of the human brain, provide challenging targets for functional mapping with neuroimaging techniques because of their small sizes and deep locations. In this study, we explore the capability of high-resolution functional magnetic resonance imaging at 4 Tesla for mapping the retinotopic organization in the lateral geniculate nucleus (LGN). Our results show that the hemifield visual stimulation only activates LGN in the contralateral hemisphere, and the lower-field and upper-field visual stimulations activate the superior and inferior portion of LGN, respectively. These results reveal a similar retinotopic organization between the human and nonhuman primate LGN and between LGN and the primary visual cortex. We conclude that high-resolution functional magnetic resonance imaging is capable of functional mapping of suborganizations in small nuclei together with cortical activation. This will have an impact for studying the thalamocortical networks in the human brain.

Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants

Mutations in Cu, Zn superoxide dismutase (SOD1) cause the neurodegenerative disease familial amyotrophic lateral sclerosis from an as-yet-unidentified toxic property(ies). Analysis in Saccharomyces cerevisiae of a broad range of human familial amyotrophic lateral sclerosis–linked SOD1 mutants (A4V, G37R, G41D, H46R, H48Q, G85R, G93C, and I113T) reveals one property common to these mutants (including two at residues that coordinate the catalytic copper): Each does indeed bind copper and scavenge oxygen-free radicals in vivo. Neither decreased copper binding nor decreased superoxide scavenging activity is a property shared by all mutants. The demonstration that shows that all mutants tested do bind copper under physiologic conditions supports a mechanism of SOD1 mutant-mediated disease arising from aberrant copper-mediated chemistry catalyzed by less tightly folded (and hence less constrained) mutant enzymes. The mutant enzymes also are shown to acquire the catalytic copper in vivo through the action of CCS, a specific copper chaperone for SOD1, which in turn suggests that a search for inhibitors of this SOD1 copper chaperone may represent a therapeutic avenue.

Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase

The mechanism by which mutations in the superoxide dismutase (SOD1) gene cause motor neuron degeneration in familial amyotrophic lateral sclerosis (ALS) is unknown. Recent reports that neuronal death in SOD1-familial ALS is apoptotic have not documented activation of cell death genes. We present evidence that the enzyme caspase-1 is activated in neurons expressing mutant SOD1 protein. Proteolytic processing characteristic of caspase-1 activation is seen both in spinal cords of transgenic ALS mice and neurally differentiated neuroblastoma (line N2a) cells with SOD1 mutations. This activation of caspase-1 is enhanced by oxidative challenge (xanthine/xanthine oxidase), which triggers cleavage and secretion of the interleukin 1β converting enzyme substrate, pro-interleukin 1β, and induces apoptosis. This N2a culture system should be an instructive in vitro model for further investigation of the proapoptotic properties of mutant SOD1.

Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice

Using adenoviruses encoding reporter genes as retrograde tracers, we assessed the capacity of motoneurons to take up and retrogradely transport adenoviral particles injected into the muscles of transgenic mice expressing the G93A human superoxide dismutase mutation, a model of amyotrophic lateral sclerosis. Surprisingly, transgene expression in the motoneurons was significantly higher in symptomatic mice than in control or presymptomatic mice. Using botulinum toxin to induce nerve sprouting at neuromuscular junctions, we showed that the unexpectedly high level of motoneurons retrograde transduction results, at least in part, from newly acquired uptake properties of the sprouts. These findings demonstrate the remarkable uptake properties of amyotrophic lateral sclerosis motoneurons in response to denervation and the rationale of using intramuscular injections of adenoviruses to overexpress therapeutic proteins in motor neuron diseases.

Inhibition of Auxin Movement from the Shoot into the Root Inhibits Lateral Root Development in Arabidopsis1

In roots two distinct polar movements of auxin have been reported that may control different developmental and growth events. To test the hypothesis that auxin derived from the shoot and transported toward the root controls lateral root development, the two polarities of auxin transport were uncoupled in Arabidopsis. Local application of the auxin-transport inhibitor naphthylphthalamic acid (NPA) at the root-shoot junction decreased the number and density of lateral roots and reduced the free indoleacetic acid (IAA) levels in the root and [3H]IAA transport into the root. Application of NPA to the basal half of or at several positions along the root only reduced lateral root density in regions that were in contact with NPA or in regions apical to the site of application. Lateral root development was restored by application of IAA apical to NPA application. Lateral root development in Arabidopsis roots was also inhibited by excision of the shoot or dark growth and this inhibition was reversible by IAA. Together, these results are consistent with auxin transport from the shoot into the root controlling lateral root development.