Feminist Success Stories - Célébrons nos réussites féministes

Abuses by international corporations, withdrawal of social services and implementation of regressive legislation continue to impoverish women and reduce the quality of their everyday lives: women have reason to be demoralized. Recognizing this challenging and difficult situation, this volume reviews women's successes at feminizing Canadian institutions. It is intended to hearten the women's movement, and show the potential for feminist change and suggest ways to realize this potential

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype

Improved detection of global copy number variation using high density, non-polymorphic oligonucleotide probes

<p>Abstract</p> <p>Background</p> <p>DNA sequence diversity within the human genome may be more greatly affected by copy number variations (CNVs) than single nucleotide polymorphisms (SNPs). Although the importance of CNVs in genome wide association studies (GWAS) is becoming widely accepted, the optimal methods for identifying these variants are still under evaluation. We have previously reported a comprehensive view of CNVs in the HapMap DNA collection using high density 500 K EA (Early Access) SNP genotyping arrays which revealed greater than 1,000 CNVs ranging in size from 1 kb to over 3 Mb. Although the arrays used most commonly for GWAS predominantly interrogate SNPs, CNV identification and detection does not necessarily require the use of DNA probes centered on polymorphic nucleotides and may even be hindered by the dependence on a successful SNP genotyping assay.</p> <p>Results</p> <p>In this study, we have designed and evaluated a high density array predicated on the use of non-polymorphic oligonucleotide probes for CNV detection. This approach effectively uncouples copy number detection from SNP genotyping and thus has the potential to significantly improve probe coverage for genome-wide CNV identification. This array, in conjunction with PCR-based, complexity-reduced DNA target, queries over 1.3 M independent NspI restriction enzyme fragments in the 200 bp to 1100 bp size range, which is a several fold increase in marker density as compared to the 500 K EA array. In addition, a novel algorithm was developed and validated to extract CNV regions and boundaries.</p> <p>Conclusion</p> <p>Using a well-characterized pair of DNA samples, close to 200 CNVs were identified, of which nearly 50% appear novel yet were independently validated using quantitative PCR. The results indicate that non-polymorphic probes provide a robust approach for CNV identification, and the increasing precision of CNV boundary delineation should allow a more complete analysis of their genomic organization.</p

Development and Assessment of a Diagnostic DNA Oligonucleotide Microarray for Detection and Typing of Meningitis-Associated Bacterial Species.

Meningitis is commonly caused by infection with a variety of bacterial or viral pathogens. Acute bacterial meningitis (ABM) can cause severe disease, which can progress rapidly to a critical life-threatening condition. Rapid diagnosis of ABM is critical, as this is most commonly associated with severe sequelae with associated high mortality and morbidity rates compared to viral meningitis, which is less severe and self-limiting. We have designed a microarray for detection and diagnosis of ABM. This has been validated using randomly amplified DNA targets (RADT), comparing buffers with or without formamide, in glass slide format or on the Alere ArrayTubeTM (Alere Technologies GmbH) microarray platform. Pathogen-specific signals were observed using purified bacterial nucleic acids and to a lesser extent using patient cerebral spinal fluid (CSF) samples, with some technical issues observed using RADT and glass slides. Repurposing the array onto the Alere ArrayTubeTM platform and using a targeted amplification system increased specific and reduced nonspecific hybridization signals using both pathogen nucleic and patient CSF DNA targets, better revealing pathogen-specific signals although sensitivity was still reduced in the latter. This diagnostic microarray is useful as a laboratory diagnostic tool for species and strain designation for ABM, rather than for primary diagnosis

Pulsating Variable Stars in the Coma Berenices dwarf spheroidal galaxy

We present B, V, I time-series photometry of the Coma Berenices dwarf spheroidal galaxy, a faint Milky Way satellite, recently discovered by the Sloan Digital Sky Survey. We have obtained V, B-V and V, V-I color-magnitude diagrams that reach V~23.0-23.2 mag showing the galaxy turnoff at V~21.7 mag, and have performed the first study of the variable star population of this new Milky Way companion. Two RR Lyrae stars (a fundamental-mode -RRab- and a first overtone -RRc- pulsator) and a short period variable with period P=0.12468 days were identified in the galaxy. The RRab star has a rather long period of P_ab=0.66971 days and is about 0.2 mag brighter than the RRc variable and other non-variable stars on the galaxy horizontal branch. In the period-amplitude diagram the RRab variable falls closer to the loci of Oosterhoff type-II systems and evolved fundamental-mode RR Lyrae stars in the Galactic globular cluster M3. The average apparent magnitude of the galaxy horizontal branch, =18.64+-0.04 mag, leads to a distance modulus for the Coma dSph mu_0=18.13+-0.08 mag, corresponding to a distance d=42^{+2}_{-1} kpc, by adopting a reddening E(B-V) = 0.045 +- 0.015 mag and a metallicity [Fe/H]=-2.53 +- 0.05 dex.Comment: 14 pages, 3 figures, Accepted for publication in ApJ

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

Improving the Efficiency of Psychological Treatment using Outcome Feedback Technology

Aims: This study evaluated the impact of applying computerized outcome feedback (OF) technology in a stepped care psychological service offering low and high intensity therapies for depression and anxiety. Methods: A group of therapists were trained to use OF based on routine outcome monitoring using depression (PHQ-9) and anxiety (GAD-7) measures. Therapists regularly reviewed expected treatment response graphs with patients and discussed cases that were “not on track” in clinical supervision. Clinical outcomes data were collected for all patients treated by this group (N = 594), six months before (controls = 349) and six months after the OF training (OF cases = 245). Symptom reductions in PHQ-9 and GAD-7 were compared between controls and OF cases using longitudinal multilevel modelling. Treatment duration and costs were compared using MANOVA. Qualitative interviews with therapists (N = 15) and patients (N = 6) were interpreted using thematic analysis. Results: OF technology was generally acceptable and feasible to integrate in routine practice. No significant between-group differences were found in post-treatment PHQ-9 or GAD-7 measures. However, OF cases had significantly lower average duration and cost of treatment compared to controls. Conclusions: After adopting OF into their practice, this group of therapists attained similar clinical outcomes but within a shorter space of time and at a reduced average cost per treatment episode. We conclude that OF can improve the efficiency of stepped care