Effects on the maternofetal unit of the rabbit model after substitution of the amniotic fluid with perfluorocarbons

Objectives: Exchanging amniotic fluid (AF) with perfluorocarbon (PFC) may serve as a medium for fetoscopic surgery. This study evaluates the distribution and physiologic effects of intraamniotic PFC as a medium for fetoscopy. Methods: Fetuses of 17 pregnant rabbits underwent either exchange of the AF with PFC, electrolyte solution (ES), or control. The quality of vision during fetoscopy was assessed in AF and PFC. After 6 h, we determined the distribution of PFC in the maternofetal unit. Results: Quality of vision during fetoscopy was better in PFC than with AF. There was no difference in fetal survival between the study groups. PFC was demonstrated on X-ray in the pharynx of 4 fetuses, and the esophagus in 1. Conclusions: PFC provided an ideal medium for fetoscopy without fetal compromise. Copyright (c) 2005 S. Karger AG, Basel

Hierarchical carbon fibre composites incorporating high loadings of carbon nanotubes

Uncured solid bisphenol-A epoxy resins containing up to 20 wt% carbon nanotubes (CNTs) were prepared using melt blending in a high shear mixer. The extrudate was ground to produce fine nanocomposite (NC) powders. This simple method produced well-dispersed NC, with CNT agglomerate sizes below 1 μm. Consolidated NCs displayed improved tensile moduli and strengths up to 3.3 GPa (+32%) and 78 MPa (+19%), respectively at 15 wt% CNT, compared to the pure cured epoxy matrix. The relatively high Tg of 39 ◦C for the uncured NC powders simplified the manufacture of composite prepregs using wet powder impregnation. The prepregs were laminated into hierarchical carbon fibre reinforced composites with improved through-thickness properties. Interlaminar shear strength improved for intermediate CNT loadings in the matrix up to 65 MPa (10 wt% CNT, +19%) but decreased at higher concentrations. Compression moduli remained constant irrespectively of CNT loading but compression strength increased with a CNT loading of 2.5 wt% to 772 MPa (+31%). The mechanical properties of the hierarchical composites reflect good consolidation (void content <3%) and excellent fibre alignment (<±0.8◦). In addition to the improved mechanical properties, incorporation of CNTs improved the through- thickness electrical conductivity up to 115 S/

American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation

The following are the recommendations of the American College of Medical Genetics (ACMG) Professional Practice and Guidelines Committee, which was convened to assist health care professionals in making decisions regarding cytogenetic diagnostic testing and counseling for mental retardation (MR) and developmental delay (DD). This document reviews available evidence concerning the value of conventional and molecular cytogenetic testing for the identification of chromosomal anomalies that play a role in the etiology of MR/DD, and, based on this evidence, specific recommendations for each method of testing are provided

Array comparative genomic hybridisation-based identification of two imbalances of chromosome 1p in a 9-year-old girl with a monosomy 1p36 related phenotype and a family history of learning difficulties: a case report

<p>Abstract</p> <p>Introduction</p> <p>Monosomy 1p36 is one of the most common terminal deletion syndromes, with an approximate incidence of 1 in every 5000 live births. This syndrome is associated with several pronounced clinical features including characteristic facial features, cardiac abnormalities, seizures and mental retardation, all of which are believed to be due to haploinsufficiency of genes within the 1p36 region. The deletion size varies from approximately 1.5 Mb to 10 Mb with the most common breakpoints located at 1p36.13 to 1p36.33. Over 70% of 1p36 deletion patients have a true terminal deletion. A further 7% have interstitial deletions and a proportion have a derivative chromosome 1 where the 1p telomere is replaced by material from another chromosome, either as a result of a de-novo rearrangement or as a consequence of malsegregation of a balanced parental translocation at meiosis.</p> <p>Case presentation</p> <p>Array comparative genomic hybridisation analysis of a 9-year-old Caucasian girl presenting with dysmorphic facial features and learning difficulties, for whom previous routine karyotyping had been normal, identified two submicroscopic rearrangements within chromosome 1p. Detection of both an insertional duplication of a region of 1p32.3 into the subtelomeric region of the short arm of a chromosome 1 homologue and a deletion within 1p36.32 of the same chromosome instigated a search for candidate genes within these regions which could be responsible for the clinical phenotype of the patient. Several genes were identified by computer-based annotation, some of which have implications in neurological and physical development.</p> <p>Conclusion</p> <p>Array comparative genomic hybridisation is providing a robust method for pinpointing regions of candidate genes associated with clinical phenotypes that extend beyond the resolution of the light microscope. This case report provides an example of how this method of analysis and the subsequent reporting of findings have proven useful in collaborative efforts to elucidate multiple gene functions from a clinical perspective.</p

Stimulus-preceding negativity in ADHD

Children with ADHD often show disrupted response preparation as indicated by attenuated stimulus-preceding negativity (SPN). This study examined response preparation in a relatively short cue-stimulus interval. No differences in SPN occurred between children with ADHD and their normal peers. A strong positive relationship was found between SPN and mean reaction time in both groups. Children with ADHD are able to mentally prepare themselves for upcoming events in short cue-stimulus intervals. © 2013 Springer-Verlag Wien

Chromosome microarray analysis as first-line test in pregnancies with a priori low risk for detection of submicroscopic chromosomal abnormalities

n this study, we aimed to explore the utility of chromosomal microarray analysis (CMA) in groups of pregnancies with a priori low risk for detection of submicroscopic chromosome abnormalities, usually not considered an indication for testing, in order to assess whether CMA improves the detection rate of prenatal chromosomal aberrations. A total of 3000 prenatal samples were processed in parallel using both whole-genome CMA and conventional karyotyping. The indications for prenatal testing included: advanced maternal age, maternal serum screening test abnormality, abnormal ultrasound findings, known abnormal fetal karyotype, parental anxiety, family history of a genetic condition and cell culture failure. The use of CMA resulted in an increased detection rate regardless of the indication for analysis. This was evident in high risk groups (abnormal ultrasound findings and abnormal fetal karyotype), in which the percentage of detection was 5.8% (7/120), and also in low risk groups, such as advanced maternal age (6/1118, 0.5%), and parental anxiety (11/1674, 0.7%). A total of 24 (0.8%) fetal conditions would have remained undiagnosed if only a standard karyotype had been performed. Importantly, 17 (0.6%) of such findings would have otherwise been overlooked if CMA was offered only to high risk pregnancies.The results of this study suggest that more widespread CMA testing of fetuses would result in a higher detection of clinically relevant chromosome abnormalities, even in low risk pregnancies. Our findings provide substantial evidence for the introduction of CMA as a first-line diagnostic test for all pregnant women undergoing invasive prenatal testing, regardless of risk factors

Tracking of unpredictable moving stimuli by pigeons

Despite being observed throughout the animal kingdom, catching a moving object is a complex task and little is known about the mechanisms that underlie this behavior in non-human animals. Three experiments examined the role of prediction in capture of a moving object by pigeons. In Experiment 1, a stimulus moved in a linear trajectory, but sometimes made an unexpected 90o turn. The sudden turn had only a modest effect on capture and error location, and the analyses suggested that the birds had adjusted their tracking to the novel motion. In Experiment 2, the role of visual input during a turn was tested by inserting disappearances (either 1.5 cm or 4.5 cm) on both the straight and turn trials. The addition of the disappearance had little effect on capture success, but delayed capture location with the larger disappearance leading to greater delay. Error analyses indicated that the birds adapted to the post-turn, post-disappearance motion. Experiment 3 tested the role of visual input when the motion disappeared behind an occluder and emerged in either a straight line or at a 90o angle. The occluder produced a disruption in capture success but did not delay capture. Error analyses indicated that the birds did not adjust their tracking to the new motion on turn trials following occlusion. The combined results indicate that pigeons can anticipate the future position of a stimulus, and can adapt to sudden, unpredictable changes in motion but do so better after a disappearance than after an occlusion

Ezrin Is Highly Expressed in Early Thymocytes, but Dispensable for T Cell Development in Mice

Ezrin/radixin/moesin (ERM) proteins are highly homologous proteins that function to link cargo molecules to the actin cytoskeleton. Ezrin and moesin are both expressed in mature lymphocytes, where they play overlapping roles in cell signaling and polarity, but their role in lymphoid development has not been explored.We characterized ERM protein expression in lymphoid tissues and analyzed the requirement for ezrin expression in lymphoid development. In wildtype mice, we found that most cells in the spleen and thymus express both ezrin and moesin, but little radixin. ERM protein expression in the thymus was differentially regulated, such that ezrin expression was highest in immature thymocytes and diminished during T cell development. In contrast, moesin expression was low in early thymocytes and upregulated during T cell development. Mice bearing a germline deletion of ezrin exhibited profound defects in the size and cellularity of the spleen and thymus, abnormal thymic architecture, diminished hematopoiesis, and increased proportions of granulocytic precursors. Further analysis using fetal liver chimeras and thymic transplants showed that ezrin expression is dispensable in hematopoietic and stromal lineages, and that most of the defects in lymphoid development in ezrin(-/-) mice likely arise as a consequence of nutritional stress.We conclude that despite high expression in lymphoid precursor cells, ezrin is dispensable for lymphoid development, most likely due to redundancy with moesin

Stochastic Cytokine Expression Induces Mixed T Helper Cell States

During eukaryotic development, the induction of a lineage-specific transcription factor typically drives differentiation of multipotent progenitor cells, while repressing that of alternative lineages. This process is often mediated by some extracellular signaling molecules, such as cytokines that can bind to cell surface receptors, leading to activation and/or repression of transcription factors. We explored the early differentiation of naive CD4 T helper (Th) cells into Th1 versus Th2 states by counting single transcripts and quantifying immunofluorescence in individual cells. Contrary to mutually exclusive expression of antagonistic transcription factors, we observed their ubiquitous co-expression in individual cells at high levels that are distinct from basal-level co-expression during lineage priming. We observed that cytokines are expressed only in a small subpopulation of cells, independent from the expression of transcription factors in these single cells. This cell-to-cell variation in the cytokine expression during the early phase of T helper cell differentiation is significantly larger than in the fully differentiated state. Upon inhibition of cytokine signaling, we observed the classic mutual exclusion of antagonistic transcription factors, thus revealing a weak intracellular network otherwise overruled by the strong signals that emanate from extracellular cytokines. These results suggest that during the early differentiation process CD4 T cells acquire a mixed Th1/Th2 state, instructed by extracellular cytokines. The interplay between extracellular and intracellular signaling components unveiled in Th1/Th2 differentiation may be a common strategy for mammalian cells to buffer against noisy cytokine expression.National Cancer Institute (U.S.). Physical Sciences-Oncology Center (U54CA143874)National Institutes of Health (U.S.) (Pioneer Award)National Institutes of Health (U.S.) (Grant R01-GM068957