Search for Genomic Alterations in Monozygotic Twins Discordant for Cleft Lip and/or Palate

Phenotypically discordant monozygotic twins offer the possibility of gene discovery through delineation of molecular abnormalities in one member of the twin pair. One proposed mechanism of discordance is postzygotically occurring genomic alterations resulting from mitotic recombination and other somatic changes. Detection of altered genomic fragments can reveal candidate gene loci that can be verified through additional analyses. We investigated this hypothesis using array comparative genomic hybridization; the 50K and 250K Affymetrix GeneChip (R) SNP arrays and an Illumina custom array consisting of 1,536 SNPs, to scan for genomic alterations in a sample of monozygotic twin pairs with discordant cleft lip and/or palate phenotypes. Paired analysis for deletions, amplifications and loss of heterozygosity, along with sequence verification of SNPs with discordant genotype calls did not reveal any genomic discordance between twin pairs in lymphocyte DNA samples. Our results demonstrate that postzygotic genomic alterations are not a common cause of monozygotic twin discordance for isolated cleft lip and/or palate. However, rare or balanced genomic alterations, tissue-specific events and small aberrations beyond the detection level of our experimental approach cannot be ruled out. The stability of genomes we observed in our study samples also suggests that detection of discordant events in other monozygotic twin pairs would be remarkable and of potential disease significance.

Oral cleft prevention program (OCPP)

Background: Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted.Methods/design: This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.Discussion: The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women.

Nesting biology and fungiculture of the fungus-growing ant, Mycetagroicus cerradensis: New light on the origin of higher-attine agriculture

The genus Mycetagroicus is perhaps the least known of all fungus-growing ant genera, having been first described in 2001 from museum specimens. A recent molecular phylogenetic analysis of the fungus-growing ants demonstrated that Mycetagroicus is the sister to all higher attine ants (Trachymyrmex, Sericomyrmex, Acromyrmex, Pseudoatta, and Atta), making it of extreme importance for understanding the transition between lower and higher attine agriculture. Four nests of Mycetagroicus cerradensis near Uberlandia, Minas Gerais, Brazil were excavated, and fungus chambers for one were located at a depth of 3.5 meters. Based on its lack of gongylidia (hyphal-tip swellings typical of higher attine cultivars), and a phylogenetic analysis of the ITS rDNA gene region, M. cerradensis cultivates a lower attine fungus in Clade 2 of lower attine (G3) fungi. This finding refines a previous estimate for the origin of higher attine agriculture, an event that can now be dated at approximately 21-25 mya in the ancestor of extant species of Trachymyrmex and Sericomyrmex.

Oral Candida albicans isolates from HIV-positive individuals have similar in vitro biofilm-forming ability and pathogenicity as invasive Candida isolates

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Modelos de regressão aleatória com diferentes estruturas de variância residual para descrever o tamanho da leitegada

Objetivou-se comparar modelos de regressão aleatória com diferentes estruturas de variância residual, a fim de se buscar a melhor modelagem para a característica tamanho da leitegada ao nascer (TLN). Utilizaram-se 1.701 registros de TLN, que foram analisados por meio de modelo animal, unicaracterística, de regressão aleatória. As regressões fixa e aleatórias foram representadas por funções contínuas sobre a ordem de parto, ajustadas por polinômios ortogonais de Legendre de ordem 3. Para averiguar a melhor modelagem para a variância residual, considerou-se a heterogeneidade de variância por meio de 1 a 7 classes de variância residual. O modelo geral de análise incluiu grupo de contemporâneo como efeito fixo; os coeficientes de regressão fixa para modelar a trajetória média da população; os coeficientes de regressão aleatória do efeito genético aditivo-direto, do comum-de-leitegada e do de ambiente permanente de animal; e o efeito aleatório residual. O teste da razão de verossimilhança, o critério de informação de Akaike e o critério de informação bayesiano de Schwarz apontaram o modelo que considerou homogeneidade de variância como o que proporcionou melhor ajuste aos dados utilizados. As herdabilidades obtidas foram próximas a zero (0,002 a 0,006). O efeito de ambiente permanente foi crescente da 1ª (0,06) à 5ª (0,28) ordem, mas decrescente desse ponto até a 7ª ordem (0,18). O comum-de-leitegada apresentou valores baixos (0,01 a 0,02). A utilização de homogeneidade de variância residual foi mais adequada para modelar as variâncias associadas à característica tamanho da leitegada ao nascer nesse conjunto de dado.

Citogenética de jumentos da raça Marchadora Brasileira

Jumentos da raça Marchadora Brasileira foram cariotipados e bandeados com C, G e NOR, sendo 2n = 62 e NF = 107. O trabalho visou a contribuir com a cariotipagem da espécie e verificar polimorfismos presentes nos animais. O cariótipo foi organizado em seis grupos, possuindo o primeiro sete pares submetacêntricos a metacêntricos, o segundo, seis subtelocêntricos, o terceiro, cinco acrocêntricos e o quarto, dois subgrupos de três cada um, subtelocêntricos e submetacêntricos. O quinto grupo continha os menores metacêntricos e os sexuais, X submetacêntrico e Y acrocêntrico, ao lado do terceiro grupo. No bandeamento C, o cromossomo 7 foi fortemente marcado, o G permitiu pareamento dos homólogos e o NOR marcou sete pares.

Genes do eixo somatotrófico e características de crescimento numa população F2 de bovinos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The effect of intracuff alkalinized 2% lidocaine on emergence coughing, sore throat, and hoarseness in smokers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Redução do amido dietético, utilizando óleo de soja, em dietas para coelhos em crescimento

Este experimento foi conduzido para avaliar os efeitos da redução do amido dietético, utilizando óleo de soja, em dietas para coelhos Nova Zelândia Branco em crescimento sobre o desempenho e rendimento de carcaça dos animais. Os coelhos foram desmamados aos 30 dias e abatidos aos 60 dias de idade. O delineamento experimental foi em blocos ao acaso com quatro tratamentos (2,2, 3,3, 4,4 e 5,5% de adição de óleo de soja às dietas) e cinco repetições com 15 animais por tratamento. Foram avaliados os ganhos de peso diário, a ingestão de alimentos diária, a conversão alimentar, a mortalidade e o rendimento de carcaça. Não houve efeito (P>0,05) dos tratamentos sobre os parâmetros avaliados. Concluiu-se que, nas condições realizadas neste trabalho, a adição de óleo de soja em dietas para coelhos em crescimento até o nível de 5,5% não afetou o desempenho produtivo.

Widespread Amazon forest tree mortality from a single cross-basin squall line event

Climate change is expected to increase the intensity of extreme precipitation events in Amazonia that in turn might produce more forest blowdowns associated with convective storms. Yet quantitative tree mortality associated with convective storms has never been reported across Amazonia, representing an important additional source of carbon to the atmosphere. Here we demonstrate that a single squall line (aligned cluster of convective storm cells) propagating across Amazonia in January, 2005, caused widespread forest tree mortality and may have contributed to the elevated mortality observed that year. Forest plot data demonstrated that the same year represented the second highest mortality rate over a 15-year annual monitoring interval. Over the Manaus region, disturbed forest patches generated by the squall followed a power-law distribution (scaling exponent alpha = 1.48) and produced a mortality of 0.3-0.5 million trees, equivalent to 30% of the observed annual deforestation reported in 2005 over the same area. Basin-wide, potential tree mortality from this one event was estimated at 542 +/- 121 million trees, equivalent to 23% of the mean annual biomass accumulation estimated for these forests. Our results highlight the vulnerability of Amazon trees to wind-driven mortality associated with convective storms. Storm intensity is expected to increase with a warming climate, which would result in additional tree mortality and carbon release to the atmosphere, with the potential to further warm the climate system. Citation: Negron-Juarez, R. I., J. Q. Chambers, G. Guimaraes, H. Zeng, C. F. M. Raupp, D. M. Marra, G. H. P. M. Ribeiro, S. S. Saatchi, B. W. Nelson, and N. Higuchi (2010), Widespread Amazon forest tree mortality from a single cross-basin squall line event, Geophys. Res. Lett., 37, L16701, doi:10.1029/2010GL043733.

Molecular phylogeny of microhylid frogs (Anura: Microhylidae) with emphasis on relationships among New World genera

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors

An involvement of the transient receptor potential vanilloid (TRPV) 1 channel in the regulation of body temperature (T b) has not been established decisively. To provide decisive evidence for such an involvement and determine its mechanisms were the aims of the present study. We synthesized a new TRPV1 antagonist, AMG0347 [(E)-N-(7-hydroxy-5,6,7,8-tetrahydronaphthalen-1- yl)-3-(2-(piperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)acrylamide], and characterized it in vitro. We then found that this drug is the most potent TRPV1 antagonist known to increase T b of rats and mice and showed (by using knock-out mice) that the entire hyperthermic effect of AMG0347 is TRPV1 dependent. AMG0347-induced hyperthermia was brought about by one or both of the two major autonomic cold-defense effector mechanisms (tail-skin vasoconstriction and/or thermogenesis), but it did not involve warmth-seeking behavior. The magnitude of the hyperthermic response depended on neither T b nor tail-skin temperature at the time of AMG0347 administration, thus indicating that AMG0347-induced hyperthermia results from blockade of tonic TRPV1 activation by nonthermal factors. AMG0347 was no more effective in causing hyperthermia when administered into the brain (intracerebroventricularly) or spinal cord (intrathecally) than when given systemically (intravenously), which indicates a peripheral site of action. We then established that localized intra-abdominal desensitization of TRPV1 channels with intraperitoneal resiniferatoxin blocks the T b response to systemic AMG0347; the extent of desensitization was determined by using a comprehensive battery of functional tests. We conclude that tonic activation of TRPV1 channels in the abdominal viscera by yet unidentified nonthermal factors inhibits skin vasoconstriction and thermogenesis, thus having a suppressive effect on T b. Copyright © 2007 Society for Neuroscience.

Generating VHDL-AMS models of digital-to-analogue converters from MATLAB®/SIMULINK®

Today, the trend within the electronics industry is for the use of rapid and advanced simulation methodologies in association with synthesis toolsets. This paper presents an approach developed to support mixed-signal circuit design and analysis. The methodology proposed shows a novel approach to the problem of developing behvioural model descriptions of mixed-signal circuit topologies, by construction of a set of subsystems, that supports the automated mapping of MATLAB®/SIMULINK® models to structural VHDL-AMS descriptions. The tool developed, named MS 2SV, reads a SIMULINK® model file and translates it to a structural VHDL-AMS code. It also creates the file structure required to simulate the translated model in the System Vision™. To validate the methodology and the developed program, the DAC08, AD7524 and AD5450 data converters were studied and initially modelled in MATLAB®/ SIMULINK®. The VHDL-AMS code generated automatically by MS 2SV, (MATLAB®/SIMULINK® to System Vision™), was then simulated in the System Vision™. The simulation results show that the proposed approach, which is based on VHDL-AMS descriptions of the original model library elements, allows for the behavioural level simulation of complex mixed-signal circuits.

Measuring and analyzing color and texture information in anatomical leaf cross sections: An approach using computer vision to aid plant species identification

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of upper-body exercise order on hormonal responses in trained men

The aim of this study was to examine acute hormonal responses after different sequences of an upper-body resistance-exercise session. Twenty men completed 2 sessions (3 sets; 70% 1-repetition maximum; 2 min passive rest between sets) of the same exercises in opposite sequences (larger to smaller vs. smaller to larger muscle-group exercises). Total testosterone (TT), free testosterone (FT), testosterone/cortisol (T/C) ratio, sex-hormone-binding globulin (SHBG), growth hormone (GH), and cortisol (C) concentrations were measured before and immediately after each sequence. The results indicate that the GH concentration increased after both sessions, but the increase was significantly greater (p < 0.05) after the sequence in which larger muscle-group exercises were performed prior to the smaller muscle-group exercises. No differences were observed between sessions for TT, FT, SHBG, C, or the T/C ratio at baseline or immediately after resistance exercise. These results indicate that performing larger muscle-group exercises first in an upper-body resistance-exercise session leads to a significantly greater GH response. This may have been due to the significantly greater exercise volume accomplished. In summary, the findings of this investigation support the common prescriptive recommendation to perform larger-muscle group exercises first during a resistance-exercise session.