XENOESTROGEN-SPECIFIC MECHANISMS OF DEVELOPMENTAL REPROGRAMMING CORRELATE WITH GENE EXPRESSION AND TUMOR DEVELOPMENT

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through estrogen (E2)/ xenoestrogen inducedrapid ER signaling, which modifies the histone methyltransferase Enhancer of Zeste homolog 2 (EZH2) via activation of the PI3K/AKT pathway. We further hypothesized that there is a xenostrogen-specific effect on this pathway altering patterns of histone modification, DNA methylation and gene expression. In addition to our novel finding that E2/DES-induced phosphorylation of EZH2 by AKT reduces the levels of H3K27me3 in vitro and in vivo, this work demonstrates in vivo that a brief neonatal exposure to GEN, in contrast to BPA, activates the PI3K/AKT pathway to regulate EZH2 and decreases H3K27me3 levels in the neonatal uterus. Given that H3K27me3 is a repressive mark that has been shown to result in DNA methylation and gene silencing we investigated the methylation of developmentally reprogrammed genes. In support of this evidence, we show that neonatal DES exposure in comparison to VEH, leads to hypomethylation of the promoter of a developmentally reprogrammed gene, Gria2, that become hyper-responsive to estrogen in the adult myometrium indicating vi that DES exposure alter gene expression via chromatin remodeling and loss of DNA methylation. In the adult uterus, GEN and BPA exposure developmentally reprogrammed expression of estrogen-responsive genes in a manner opposite of one another, correlating with our previous data. Furthermore, the ability of GEN and BPA to developmental reprogram gene expression correlated with tumor incidence and multiplicity. These data show that xenoestrogens have unique effects on the activation of non-genomic signaling in the developing uterus that promotes epigenetic and genetic alterations, which are predictive of developmental reprogramming and correlate with their ability to modulate hormone-dependent tumor development

Efficient Sparse Matrix-Vector Multiplication on GPUs Using the CSR Storage Format.

Abstract-The performance of sparse matrix vector multiplication (SpMV) is important to computational scientists. Compressed sparse row (CSR) is the most frequently used format to store sparse matrices. However, CSR-based SpMV on graphics processing units (GPUs) has poor performance due to irregular memory access patterns, load imbalance, and reduced parallelism. This has led researchers to propose new storage formats. Unfortunately, dynamically transforming CSR into these formats has significant runtime and storage overheads. We propose a novel algorithm, CSR-Adaptive, which keeps the CSR format intact and maps well to GPUs. Our implementation addresses the aforementioned challenges by (i) efficiently accessing DRAM by streaming data into the local scratchpad memory and (ii) dynamically assigning different numbers of rows to each parallel GPU compute unit. CSR-Adaptive achieves an average speedup of 14.7× over existing CSR-based algorithms and 2.3× over clSpMV cocktail, which uses an assortment of matrix formats

Plastic and Reconstructive Surgery Advance Online Article

Background: The aim of this study was to evaluate the efficacy, safety profile, and complications associated with mandibular distraction osteogenesis performed in infants weighing less than 4 kg with Robin sequence. Methods: An 11-year retrospective review of all infants (younger than 6 months) with mandibular distraction osteogenesis–treated Robin sequence was performed. Patients weighing less than 4 kg (experimental) and 4 kg or more (control) who underwent mandibular distraction osteogenesis were compared. Demographics, medical comorbidities, improvement in apnea/hypopnea index, need for tracheostomy, repeated distraction, and complications were evaluated. Results: One hundred twenty-one patients underwent mandibular distraction osteogenesis. Eighty-one patients weighed less than 4 kg and 40 weighed 4 kg or more. The mean follow-up was 2.8 years in patients weighing less than 4 kg and 3.0 years in the control group. Mean age and weight at the time of distraction were 23 days and 3.1 kg, respectively, in the study group; and 2.7 years and 11 kg, respectively, in the control group. There was no significant difference in success of mandibular distraction osteogenesis to treat airway obstruction in the group weighing less than 4 kg compared with the control group (92.6 percent versus 88.9 percent; p = 0.49). The most common complication in each group was surgical-site infection (9.9 percent and 20.0 percent; p = 0.15). Overall complication rates were similar between the two groups (17.3 percent versus 25.0 percent; p = 0.34). The rates of repeated distraction were similar between the two groups (6.3 percent and 13.5 percent; p = 0.28). Conclusions: Mandibular distraction osteogenesis is a safe and effective treatment modality for infants weighing less than 4 kg with severe airway obstruction. The efficacy, safety, and complication profiles are not significantly different from those of larger patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III

Conformation of the Transmembrane Domain of the Anthrax Toxin Receptor

Restauració dels vitrallsFoto final, plafó a6, cara interna, amb llum a través. Geomètric

Hydrophobic Coupling of Lipid Bilayer Energetics to Channel Function

The hydrophobic coupling between membrane-spanning proteins and the lipid bilayer core causes the bilayer thickness to vary locally as proteins and other “defects” are embedded in the bilayer. These bilayer deformations incur an energetic cost that, in principle, could couple membrane proteins to each other, causing them to associate in the plane of the membrane and thereby coupling them functionally. We demonstrate the existence of such bilayer-mediated coupling at the single-molecule level using single-barreled as well as double-barreled gramicidin channels in which two gramicidin subunits are covalently linked by a water-soluble, flexible linker. When a covalently attached pair of gramicidin subunits associates with a second attached pair to form a double-barreled channel, the lifetime of both channels in the assembly increases from hundreds of milliseconds to a hundred seconds—and the conductance of each channel in the side-by-side pair is almost 10% higher than the conductance of the corresponding single-barreled channels. The double-barreled channels are stabilized some 100,000-fold relative to their single-barreled counterparts. This stabilization arises from: first, the local increase in monomer concentration around a single-barreled channel formed by two covalently linked gramicidins, which increases the rate of double-barreled channel formation; and second, from the increased lifetime of the double-barreled channels. The latter result suggests that the two barrels of the construct associate laterally. The underlying cause for this lateral association most likely is the bilayer deformation energy associated with channel formation. More generally, the results suggest that the mechanical properties of the host bilayer may cause the kinetics of membrane protein conformational transitions to depend on the conformational states of the neighboring proteins

Ralgro-implanted bulls: Performance, carcass characteristics, longissimus palatability and carcass electrical stimulation

Twenty of 40 Angus bulls were implanted (I) five times with 36 mg of Ralgro| at average intervals of 106 d, beginning near birth. All bulls and their dams were on bluestem pasture initially and, at an average age of 320 d bulls were fed a concentrate diet until they were slaughtered, weighing either 454 or 499 kg. One side of each carcass was electrically stimulated. Average daily gain and feed efficiency of I bulls improved 6.5 to 10.4% and 7.9 to 8.1%, respectively, depending upon the end point comparison with nonimplanted (NI) bulls. Implanted bulls attained their slaughter weights 42 d sooner than did NI bulls. Implantation decreased (P<.05) penis weight and length, testicle weight, volume and density, but did not affect (P>.05) seminal vesicle and pituitary weights. Carcasses from I bulls had more (P<.05) skeletal ossification and were fatter than carcasses from NI bulls. Marbling scores, quality grades and longissimus cooking losses and juiciness scores were not affected (P>.05) by implantation. Taste panel flavor intensity and detectable connective tissue scores were higher (P<.05) for steaks from I bulls than from NI bulls. Longissimus steak tenderness evaluations were higher (P<.05) for both I slaughter groups than for the NI light-weight group and were higher (P<.05) for the I lightweight group than for the NI heavy-weight group. Longissimus tenderness tended (P = .11) to be higher for steaks from the I heavy-weight group than those from the NI heavy-weight group. Electrical stimulation produced (P<.05) a softer, coarser textured lean, but it did not affect lean color, marbling or quality grade. Steaks from electrically stimulated sides tended to have higher (P = .09) myofibrillar tenderness scores and lower (P = .06) flavor scores than steaks from nonstimulated sides

Mass Flows in Cometary UCHII Regions

High spectral and spatial resolution, mid-infrared fine structure line observations toward two ultracompact HII (UCHII) regions (G29.96 -0.02 and Mon R2) allow us to study the structure and kinematics of cometary UCHII regions. In our earlier study of Mon R2, we showed that highly organized mass motions accounted for most of the velocity structure in that UCHII region. In this work, we show that the kinematics in both Mon R2 and G29.96 are consistent with motion along an approximately paraboloidal shell. We model the velocity structure seen in our mapping data and test the stellar wind bow shock model for such paraboloidal like flows. The observations and the simulation indicate that the ram pressures of the stellar wind and ambient interstellar medium cause the accumulated mass in the bow shock to flow along the surface of the shock. A relaxation code reproduces the mass flow's velocity structure as derived by the analytical solution. It further predicts that the pressure gradient along the flow can accelerate ionized gas to a speed higher than that of the moving star. In the original bow shock model, the star speed relative to the ambient medium was considered to be the exit speed of ionized gas in the shell.Comment: 34 pages, including 14 figures and 1 table, to be published in ApJ, September 200

Language support for immigrant children: a study of state schools in the UK and US

In recent decades, immigrants, refugees and asylum seekers have sought a new way of life in large numbers, often leaving their countries of origin behind in search of places that offer a better way of life. The purpose of this study was to investigate how elementary and middle school students in state schools in Reading, England (primarily speakers of Asian languages), and Richmond, Virginia (primarily speakers of Spanish), were supported academically, when most children’s first language was not English. The authors were interested in exploring whether or not there were cultural or structural differences in the way each country helped or hindered these students as they progressed through the school systems. Three UK schools in a district of approximately 100,000 and three US schools in a district of approximately 250,000 were the focus of this exploration from 2000 to 2003. Findings indicated that there were cultural and legislative differences and similarities. Teachers and administrators in both countries attempted to provide services with limited and sometimes diminishing resources. Community support varied based on resources, attitudes toward various ethnic groups, and the coping strategies adopted by these groups in their new environments. Marked differences appeared with regard to the manner in which assessments took place and how the results were made available to the public