Voices of girls with disabilities in rural Iran

This paper investigates the interaction of gender, disability and education in rural Iran, which is a relatively unexplored field of research. The responses of 10 female students with disabilities from Isfahan indicated that the obstacles they faced included marginalization, difficulties in getting from home to school, difficulties within the school building itself, and discrimination by teachers, classmates and school authorities. The data collected for the study contain a wide range of conservative gendered discourses, and show how traditional gender beliefs interact with disability to aggravate the problems faced in education by young women with disabilities. It is hoped that the findings will raise awareness among policy-makers of the many formidable obstacles that make it difficult for young women with disabilities to achieve their full potential in education

B-MYB Is Essential for Normal Cell Cycle Progression and Chromosomal Stability of Embryonic Stem Cells

Background: The transcription factor B-Myb is present in all proliferating cells, and in mice engineered to remove this gene, embryos die in utero just after implantation due to inner cell mass defects. This lethal phenotype has generally been attributed to a proliferation defect in the cell cycle phase of G1. Methodology/Principal Findings: In the present study, we show that the major cell cycle defect in murine embryonic stem (mES) cells occurs in G2/M. Specifically, knockdown of B-Myb by short-hairpin RNAs results in delayed transit through G2/M, severe mitotic spindle and centrosome defects, and in polyploidy. Moreover, many euploid mES cells that are transiently deficient in B-Myb become aneuploid and can no longer be considered viable. Knockdown of B-Myb in mES cells also decreases Oct4 RNA and protein abundance, while over-expression of B-MYB modestly up-regulates pou5f1 gene expression. The coordinated changes in B-Myb and Oct4 expression are due, at least partly, to the ability of B-Myb to directly modulate pou5f1 gene promoter activity in vitro. Ultimately, the loss of B-Myb and associated loss of Oct4 lead to an increase in early markers of differentiation prior to the activation of caspase-mediated programmed cell death. Conclusions/Significance: Appropriate B-Myb expression is critical to the maintenance of chromosomally stable and pluripotent ES cells, but its absence promotes chromosomal instability that results in either aneuploidy or differentiation-associated cell death

A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan

BackgroundAging is associated with increased levels of reactive oxygen species and inflammation that disrupt proteostasis and mitochondrial function and leads to organism-wide frailty later in life. ARA290 (cibinetide), an 11-aa non-hematopoietic peptide sequence within the cardioprotective domain of erythropoietin, mediates tissue protection by reducing inflammation and fibrosis. Age-associated cardiac inflammation is linked to structural and functional changes in the heart, including mitochondrial dysfunction, impaired proteostasis, hypertrophic cardiac remodeling, and contractile dysfunction. Can ARA290 ameliorate these age-associated cardiac changes and the severity of frailty in advanced age?MethodsWe conducted an integrated longitudinal (n = 48) and cross-sectional (n = 144) 15 months randomized controlled trial in which 18-month-old Fischer 344 x Brown Norway rats were randomly assigned to either receive chronic ARA290 treatment or saline. Serial echocardiography, tail blood pressure and body weight were evaluated repeatedly at 4-month intervals. A frailty index was calculated at the final timepoint (33 months of age). Tissues were harvested at 4-month intervals to define inflammatory markers and left ventricular tissue remodeling. Mitochondrial and myocardial cell health was assessed in isolated left ventricular myocytes. Kaplan–Meier survival curves were established. Mixed ANOVA tests and linear mixed regression analysis were employed to determine the effects of age, treatment, and age-treatment interactions.ResultsChronic ARA290 treatment mitigated age-related increases in the cardiac non-myocyte to myocyte ratio, infiltrating leukocytes and monocytes, pro-inflammatory cytokines, total NF-κB, and p-NF-κB. Additionally, ARA290 treatment enhanced cardiomyocyte autophagy flux and reduced cellular accumulation of lipofuscin. The cardiomyocyte mitochondrial permeability transition pore response to oxidant stress was desensitized following chronic ARA290 treatment. Concurrently, ARA290 significantly blunted the age-associated elevation in blood pressure and preserved the LV ejection fraction. Finally, ARA290 preserved body weight and significantly reduced other markers of organism-wide frailty at the end of life.ConclusionAdministration of ARA290 reduces cell and tissue inflammation, mitigates structural and functional changes within the cardiovascular system leading to amelioration of frailty and preserved healthspan

Advances in atomic force microscopy

This article reviews the progress of atomic force microscopy (AFM) in ultra-high vacuum, starting with its invention and covering most of the recent developments. Today, dynamic force microscopy allows to image surfaces of conductors \emph{and} insulators in vacuum with atomic resolution. The mostly used technique for atomic resolution AFM in vacuum is frequency modulation AFM (FM-AFM). This technique, as well as other dynamic AFM methods, are explained in detail in this article. In the last few years many groups have expanded the empirical knowledge and deepened the theoretical understanding of FM-AFM. Consequently, the spatial resolution and ease of use have been increased dramatically. Vacuum AFM opens up new classes of experiments, ranging from imaging of insulators with true atomic resolution to the measurement of forces between individual atoms.Comment: In press (Reviews of Modern Physics, scheduled for July 2003), 86 pages, 44 figure

The valves and tributary veins of the saphenofemoral junction: ultrasound findings in normal limbs

In the past the saphenofemoral junction (SFJ) for the surgeon was regarded as a simple conduit to be obliterated. With modern ultrasound we can distinguish the components of this complex structure and examine their haemodynamic function and suggest more haemodynamically-focused interventions. Despite this, there are no ultrasound studies describing the components of the normal SFJ and their haemodynamic significance. Patients attending our vascular laboratory with suspected deep vein thrombosis were screened and the SFJ in 75 limbs with no physiological or haemodynamic abnormalities were examined. The terminal (TV) and preterminal (PTV) valve morphology and the distance from the SFJ were assessed. The number of tributaries and their position relative to these valves was also examined. TV and PTVs were identified on ultrasound in all 75 limbs. TVs were found at a mean distance of 0.4 cm (range 0–1.2 cm) from the SFJ. Nearly a third of all limbs had at least one tributary vein identified superior to the TV. The greater the distance to the TV, the greater the number of tributary veins one should expect to find superior to the TV. PTV location was more variable. PTVs were identified at a mean distance of 3.1 cm (range 0.4–8.7 cm), giving rise to a large number of configurations of tributary veins in the intervalve space. This study characterizes the ultrasound appearances of the normal SFJ and compares these with reported anatomical studies. Valves can be consistently identified whereas the number and location of the tributaries are very variable. This should inform planning of haemodynamically-focused treatment at the SFJ

Linkage of pluripotent stem cell-associated transcripts to regulatory gene networks

These journal issues entitled: Stem Cells, Tissue Regeneration and Repair (free suppl.)Knowledge of the transcriptional circuitry responsible for pluripotentiality and self-renewal in embryonic stem cells is tantamount to understanding early mammalian development and a prerequisite to determining their therapeutic potential. Various techniques have employed genomics to identify transcripts that were abundant in stem cells, in an attempt to define the molecular basis of 'stemness'. In this study, we have extended traditional genomic analyses to identify cis-elements that might be implicated in the control of embryonic stem cell-restricted gene promoters. The strategy relied on the generation of a problem-specific list from serial analysis of gene expression profiles and subsequent promoter analyses to identify frameworks of multiple cis-elements conserved in space and orientation among genes from the problem-specific list. Subsequent experimental data suggest that 2 novel transcription factors, B-Myb and Maz, predicted from these models, are implicated either in the maintenance of the undifferentiated stem cell state or in early steps of differentiation. Copyright © 2008 S. Karger AG.link_to_OA_fulltex