What Should the Goals Be? Employment Equity for Female Faculty in Canada

This paper investigates the process of setting employment equity goals and timetables for female faculty in Canadian universities. First, the paper identifies the conditions under which a goal of a 50-50 balance between men and women faculty members by the year 2000 can be achieved. Second, it identifies criteria for evaluating the reasonableness of this goal. Third, given that such criteria as external availability, impact on labour demand and fairness suggest that this goal may not be reasonable, the question becomes: what should the goals be? The paper addresses this question by analyzing the impact of alternative hiring targets (reflecting alternative assumptions about external availability) on the gender composition of faculty in the year 2000. These hiring targets range from an extremely conservative 16.8% female to an optimistic 44.4% female. Under appropriate assumptions, these yield gender composition estimates ranging from 17.5% to 35.4%. While recognizing that availability will vary across universities, it is hoped that the estimates provided herein will inform debates on setting employment equity goals: l)by illustrating and elaborating on a methodology for establishing goals and timetables; and 2) by providing lower-bound and upper-bound estimates (along with estimates based upon moderate assumptions) to illustrate the range of possibilities under Canadian employment equity policy.Cet article porte sur le mode d'établissement d'objectifs et de calendriers relatifs à l'équité en matière d'emploi pour les professeurs féminins dans les universités canadiennes. Il définit d'abord dans quel contexte on peut réaliser d'ici l'an 2000 l'équilibre entre le nombre d'hommes et celui de femmes chez les professeurs d'université. Il établit ensuite des critères servant à déterminer si cet objectif est raisonnable. En troisième lieu, puisque des critères comme la disponibilité externe, les effets sur la demande de professeurs et la justice laissent supposer que cet objectif pourrait ne pas être raisonnable, la question devient celle-ci : quels objectifs devrait-on fixer? Le document traite de cette question en analysant les effets de différents objectifs en matière d'embauche (reflétant différentes hypothè-ses quant à la disponibilité externe) sur la composition d'après le sexe du corps professoral, en l'an 2000. Ces objectifs en matière d'embauche varient d'une proportion extrêmement conservatrice de 16,8 % de femmes jusqu'à une proportion optimiste de 44,4% de femmes. Des hypothèses valables nous donnent des estimations variant de 17,5 % à 35,4 %. Tout en reconnaissant que la disponibilité variera d'une université à l'autre, on espère que les estimations fournies permettront des discussions éclairées sur l'établissement d'objectifs relatifs à l'équité en matière d'emploi 1) en élaborant et en illustrant une méthodologie pour définir des objectifs et des calendriers, et 2) en fournissant des estimations extrêmes (ainsi que d'autres fondées sur des hypothèses modérées) afin d'illustrer les diverses possibilités qui s'offrent dans le cadre de la politique canadienne sur l'équité en matière d'emploi

Removal of a frameshift between the hsdM and hsdS genes of the EcoKI Type IA DNA restriction and modification system produces a new type of system and links the different families of Type I systems

The EcoKI DNA methyltransferase is a trimeric protein comprised of two modification subunits (M) and one sequence specificity subunit (S). This enzyme forms the core of the EcoKI restriction/modification (RM) enzyme. The 3′ end of the gene encoding the M subunit overlaps by 1 nt the start of the gene for the S subunit. Translation from the two different open reading frames is translationally coupled. Mutagenesis to remove the frameshift and fuse the two subunits together produces a functional RM enzyme in vivo with the same properties as the natural EcoKI system. The fusion protein can be purified and forms an active restriction enzyme upon addition of restriction subunits and of additional M subunit. The Type I RM systems are grouped into families, IA to IE, defined by complementation, hybridization and sequence similarity. The fusion protein forms an evolutionary intermediate form lying between the Type IA family of RM enzymes and the Type IB family of RM enzymes which have the frameshift located at a different part of the gene sequence

Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance

The ardA gene, found in many prokaryotes including important pathogenic species, allows associated mobile genetic elements to evade the ubiquitous Type I DNA restriction systems and thereby assist the spread of resistance genes in bacterial populations. As such, ardA contributes to a major healthcare problem. We have solved the structure of the ArdA protein from the conjugative transposon Tn916 and find that it has a novel extremely elongated curved cylindrical structure with defined helical grooves. The high density of aspartate and glutamate residues on the surface follow a helical pattern and the whole protein mimics a 42-base pair stretch of B-form DNA making ArdA by far the largest DNA mimic known. Each monomer of this dimeric structure comprises three alpha–beta domains, each with a different fold. These domains have the same fold as previously determined proteins possessing entirely different functions. This DNA mimicry explains how ArdA can bind and inhibit the Type I restriction enzymes and we demonstrate that 6 different ardA from pathogenic bacteria can function in Escherichia coli hosting a range of different Type I restriction systems

What potential has tobacco control for reducing health inequalities? The New Zealand situation

In this Commentary, we aim to synthesize recent epidemiological data on tobacco and health inequalities for New Zealand and present it in new ways. We also aim to describe both existing and potential tobacco control responses for addressing these inequalities. In New Zealand smoking prevalence is higher amongst Māori and Pacific peoples (compared to those of "New Zealand European" ethnicity) and amongst those with low socioeconomic position (SEP). Consequently the smoking-related mortality burden is higher among these populations. Regarding the gap in mortality between low and high socioeconomic groups, 21% and 11% of this gap for men and women was estimated to be due to smoking in 1996–99. Regarding the gap in mortality between Māori and non-Māori/non-Pacific, 5% and 8% of this gap for men and women was estimated to be due to smoking. The estimates from both these studies are probably moderate underestimates due to misclassification bias of smoking status. Despite the modest relative contribution of smoking to these gaps, the absolute number of smoking-attributable deaths is sizable and amenable to policy and health sector responses. There is some evidence, from New Zealand and elsewhere, for interventions that reduce smoking by low-income populations and indigenous peoples. These include tobacco taxation, thematically appropriate mass media campaigns, and appropriate smoking cessation support services. But there are as yet untried interventions with major potential. A key one is for a tighter regulatory framework that could rapidly shift the nicotine market towards pharmaceutical-grade nicotine (or smokeless tobacco products) and away from smoked tobacco

Hypoinsulinemia Regulates Amphetamine-Induced Reverse Transport of Dopamine

The behavioral effects of psychomotor stimulants such as amphetamine (AMPH) arise from their ability to elicit increases in extracellular dopamine (DA). These AMPH-induced increases are achieved by DA transporter (DAT)-mediated transmitter efflux. Recently, we have shown that AMPH self-administration is reduced in rats that have been depleted of insulin with the diabetogenic agent streptozotocin (STZ). In vitro studies suggest that hypoinsulinemia may regulate the actions of AMPH by inhibiting the insulin downstream effectors phosphotidylinositol 3-kinase (PI3K) and protein kinase B (PKB, or Akt), which we have previously shown are able to fine-tune DAT cell-surface expression. Here, we demonstrate that striatal Akt function, as well as DAT cell-surface expression, are significantly reduced by STZ. In addition, our data show that the release of DA, determined by high-speed chronoamperometry (HSCA) in the striatum, in response to AMPH, is severely impaired in these insulin-deficient rats. Importantly, selective inhibition of PI3K with LY294002 within the striatum results in a profound reduction in the subsequent potential for AMPH to evoke DA efflux. Consistent with our biochemical and in vivo electrochemical data, findings from functional magnetic resonance imaging experiments reveal that the ability of AMPH to elicit positive blood oxygen level–dependent signal changes in the striatum is significantly blunted in STZ-treated rats. Finally, local infusion of insulin into the striatum of STZ-treated animals significantly recovers the ability of AMPH to stimulate DA release as measured by high-speed chronoamperometry. The present studies establish that PI3K signaling regulates the neurochemical actions of AMPH-like psychomotor stimulants. These data suggest that insulin signaling pathways may represent a novel mechanism for regulating DA transmission, one which may be targeted for the treatment of AMPH abuse and potentially other dopaminergic disorders

The structure of the KlcA and ArdB proteins reveals a novel fold and antirestriction activity against Type I DNA restriction systems in vivo but not in vitro

Plasmids, conjugative transposons and phage frequently encode anti-restriction proteins to enhance their chances of entering a new bacterial host that is highly likely to contain a Type I DNA restriction and modification (RM) system. The RM system usually destroys the invading DNA. Some of the anti-restriction proteins are DNA mimics and bind to the RM enzyme to prevent it binding to DNA. In this article, we characterize ArdB anti-restriction proteins and their close homologues, the KlcA proteins from a range of mobile genetic elements; including an ArdB encoded on a pathogenicity island from uropathogenic Escherichia coli and a KlcA from an IncP-1b plasmid, pBP136 isolated from Bordetella pertussis. We show that all the ArdB and KlcA act as anti-restriction proteins and inhibit the four main families of Type I RM systems in vivo, but fail to block the restriction endonuclease activity of the archetypal Type I RM enzyme, EcoKI, in vitro indicating that the action of ArdB is indirect and very different from that of the DNA mimics. We also present the structure determined by NMR spectroscopy of the pBP136 KlcA protein. The structure shows a novel protein fold and it is clearly not a DNA structural mimic

Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.

Despite being a canonical presenting feature of mitochondrial disease, the genetic basis of progressive external ophthalmoplegia remains unknown in a large proportion of patients. Here we show that mutations in SPG7 are a novel cause of progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. After excluding known causes, whole exome sequencing, targeted Sanger sequencing and multiplex ligation-dependent probe amplification analysis were used to study 68 adult patients with progressive external ophthalmoplegia either with or without multiple mitochondrial DNA deletions in skeletal muscle. Nine patients (eight probands) were found to carry compound heterozygous SPG7 mutations, including three novel mutations: two missense mutations c.2221G>A; p.(Glu741Lys), c.2224G>A; p.(Asp742Asn), a truncating mutation c.861dupT; p.Asn288*, and seven previously reported mutations. We identified a further six patients with single heterozygous mutations in SPG7, including two further novel mutations: c.184-3C>T (predicted to remove a splice site before exon 2) and c.1067C>T; p.(Thr356Met). The clinical phenotype typically developed in mid-adult life with either progressive external ophthalmoplegia/ptosis and spastic ataxia, or a progressive ataxic disorder. Dysphagia and proximal myopathy were common, but urinary symptoms were rare, despite the spasticity. Functional studies included transcript analysis, proteomics, mitochondrial network analysis, single fibre mitochondrial DNA analysis and deep re-sequencing of mitochondrial DNA. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle, and mitochondrial fusion in patient fibroblasts associated with the clonal expansion of mitochondrial DNA mutations. In conclusion, the SPG7 gene should be screened in patients in whom a disorder of mitochondrial DNA maintenance is suspected when spastic ataxia is prominent. The complex neurological phenotype is likely a result of the clonal expansion of secondary mitochondrial DNA mutations modulating the phenotype, driven by compensatory mitochondrial biogenesis

Voting Characteristics of Individuals With Traumatic Brain Injury

Voting is the foundation of democracy. Limited data exist about voting characteristics of individuals with neurologic impairment including those living with a traumatic brain injury (TBI). To statistically examine voting characteristics using a convenience sample of registered voters with TBI during elections held in Mecklenburg County, North Carolina—2007, 2008. Data were collected on 51 participants with TBI during May 2007, 2008 general, and 2008 Presidential Election. (i) There was a significant difference between the Competence Assessment Tool for Voting (CAT‐V) total score of participants with TBI who voted and the CAT‐V total score of participants with TBI who did not vote and the CAT‐V total score predicted voting; (ii) the age of the participants with TBI was predictive of voting; and (iii) being married was inversely related to voting. We find that there is variation in voting even among this small sample interviewed for the present study, and that the variation is predictable. Those with the highest CAT‐Vs are most likely to vote. In addition, we find that traditional predictors of voting simply are not predictors among this TBI group, and even one, whether the person is married, has a negative effect on voting

Interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in human epithelial cancer cells

Epidermal growth factor receptor (EGFR) is an important regulator of epithelial cell growth and survival in normal and cancerous tissues and is a principal therapeutic target for cancer treatment. EGFR is associated in epithelial cells with the heavily glycosylated transmembrane mucin protein MUC1, a natural ligand of galectin-3 that is overexpressed in cancer. This study reveals that the expression of cell surface MUC1 is a critical enhancer of EGF-induced EGFR activation in human breast and colon cancer cells. Both the MUC1 extracellular and intracellular domains are involved in EGFR activation but the predominant influence comes from its extracellular domain. Binding of galectin-3 to the MUC1 extracellular domain induces MUC1 cell surface polarization and increases MUC1–EGFR association. This leads to a rapid increase of EGFR homo-/hetero-dimerization and subsequently increased, and also prolonged, EGFR activation and signalling. This effect requires both the galectin-3 C-terminal carbohydrate recognition domain and its N-terminal ligand multi-merization domain. Thus, interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in epithelial cancer cells. As MUC1 and galectin-3 are both commonly overexpressed in most types of epithelial cancers, their interaction and impact on EGFR activation likely makes important contribution to EGFR-associated tumorigenesis and cancer progression and may also influence the effectiveness of EGFR-targeted cancer therapy