Genetic characterization of clinical and agri-food isolates of multi drug resistant Salmonella enterica serovar Heidelberg from Canada

<p>Abstract</p> <p>Background</p> <p><it>Salmonella enterica </it>serovar Heidelberg ranks amongst the most prevalent causes of human salmonellosis in Canada and an increase in resistance to extended spectrum cephalosporins (ESC) has been observed by the Canadian Integrated Program for Antimicrobial Resistance Surveillance. This study examined the genetic relationship between <it>S</it>. Heidelberg isolates from livestock, abattoir, retail meat, and clinical human specimens to determine whether there was a link between the emergence of MDR <it>S</it>. Heidelberg in chicken agri-food sources and the simultaneous increase of MDR <it>S</it>. Heidelberg in human clinical samples.</p> <p>Results</p> <p>Chromosomal genetic homogeneity was observed by pulsed-field gel electrophoresis (PFGE), DNA sequence-based typing (SBT) and DNA microarray-based comparative genomic hybridization (CGH). Sixty one percent of isolates were indistinguishable by PFGE conducted using <it>Xba</it>I and <it>Bln</it>I restriction enzymes. An additional 15% of isolates had PFGE patterns that were closely related to the main cluster. SBT did not identify DNA polymorphisms and CGH revealed only genetic differences between the reference <it>S</it>. Typhimurium strain and <it>S</it>. Heidelberg isolates. Genetic variation observed by CGH between <it>S</it>. Heidelberg isolates could be attributed to experimental variation. Alternatively, plasmid content was responsible for differences in antimicrobial susceptibility, and restriction fragment length polymorphism (RFLP) analyses followed by replicon typing identified two divergent plasmid types responsible for ESC resistance.</p> <p>Conclusion</p> <p>Due to the overall limited genetic diversity among the isolates, it was not possible to identify variable traits that would be suitable for source tracking between human and agri-food isolates of <it>S</it>. Heidelberg in Canada.</p

Joint Effects: A Pilot Investigation of the Impact of Bipolar Disorder and Marijuana Use on Cognitive Function and Mood

Marijuana is the most widely used illicit substance in those diagnosed with bipolar I disorder. However, there is conflicting evidence as to whether marijuana may alleviate or exacerbate mood symptomatology. As bipolar disorder and marijuana use are individually associated with cognitive impairment, it also remains unclear whether there is an additive effect on cognition when bipolar patients use marijuana. The current study aimed to determine the impact of marijuana on mood in bipolar patients and to examine whether marijuana confers an additional negative impact on cognitive function. Twelve patients with bipolar disorder who smoke marijuana (MJBP), 18 bipolar patients who do not smoke (BP), 23 marijuana smokers without other Axis 1 pathology (MJ), and 21 healthy controls (HC) completed a neuropsychological battery. Further, using ecological momentary assessment, participants rated their mood three times daily as well as after each instance of marijuana use over a four-week period. Results revealed that although the MJ, BP, and MJBP groups each exhibited some degree of cognitive impairment relative to HCs, no significant differences between the BP and MJBP groups were apparent, providing no evidence of an additive negative impact of BPD and MJ use on cognition. Additionally, ecological momentary assessment analyses indicated alleviation of mood symptoms in the MJBP group after marijuana use; MJBP participants experienced a substantial decrease in a composite measure of mood symptoms. Findings suggest that for some bipolar patients, marijuana may result in partial alleviation of clinical symptoms. Moreover, this improvement is not at the expense of additional cognitive impairment

Making the Case for a Null Effects Framework in Environmental Education and K-12 Academic Outcomes: When “Just as Good” Is a Great Thing

As K-12 audiences represent a major proportion of environmental education (EE) audiences, academics should be an outcome of interest in EE research and evaluation. However, research around links between EE and academic outcomes (e.g., grades, test scores) is scant. Reasons for limited research on EE and academic outcomes may include disinterest in academic outcomes, assertion that academic outcomes are poor measures of learning, and normative biases against publishing null or negative effects within academia. We argue for adoption of a null effects framework for linking EE and academic outcomes. We begin by outlining what we mean by a null effects framework and then suggest reasons why the EE community should adopt it. Specifically, a null effects framework embraces and celebrates research demonstrating no difference in traditional academic outcomes associated with EE curricula and more traditional classroom instruction. We describe key aspects of operationalizing a null effects framework, including use of key statistical procedures (e.g., measuring power), and changes in peer review associated with emphasizing measures of evidence beyond hypotheses testing and p-values. We conclude by describing how this approach matches EE objectives, strengthens links to academic outcomes without being bound by them, avoids setting unrealistic expectations for EE, and highlights the myriad of non-academic co-benefits offered by EE. As including EE in schools is the best opportunity for reaching the most learners in terms of numbers and diversity, we offer a null effects framework as an approach that can boost adoption of EE where it is arguably needed most

The Iowa Homemaker vol.21, no.3

Freshmen – Please Note, page 2 Hospital Research, Ann Koebel, page 3 Orchids to Pat, page 4 The Army Eats Well, Mary I. Barber, page 5 Making Things Grow, Betty Ann Iverson, page 6 Look Before You Snap, Kathryn Monson, page 7 Major Departments on Review, Elizabeth Murfield, page 8 Patriotic Sally, Patricia Hayes, page 10 What’s New in Home Economics, Dorothy Olson, page 12 Summer Job Holders Reap Experience, page 14 A List of Don’ts, Costume Design Class, page 15 We Salute Campus Leaders, Margaret Kirchner, page 16 Home Economics Looks to Future, M. L. Morton, page 17 Behind Bright Jackets, Julie Wendel, page 18 Alums in the News, Mary Elizabeth Sather, page 20 Nutrition for Defense, Dorothy Ann Roost, page 22 That Personal Touch, Margaret Ann Clarke, page 23 Journalistic Spindles, Elizabeth Hanson, page 2

The Role of IRE1α in the Degradation of Insulin mRNA in Pancreatic β-Cells

The endoplasmic reticulum (ER) is a cellular compartment for the biosynthesis and folding of newly synthesized secretory proteins such as insulin. Perturbations to ER homeostasis cause ER stress and subsequently activate cell signaling pathways, collectively known as the Unfolded Protein Response (UPR). IRE1α is a central component of the UPR. In pancreatic β-cells, IRE1α also functions in the regulation of insulin biosynthesis.Here we report that hyperactivation of IRE1α caused by chronic high glucose treatment or IRE1α overexpression leads to insulin mRNA degradation in pancreatic β-cells. Inhibition of IRE1α signaling using its dominant negative form prevents insulin mRNA degradation. Islets from mice heterozygous for IRE1α retain expression of more insulin mRNA after chronic high glucose treatment than do their wild-type littermates.These results reveal a role of IRE1α in insulin mRNA expression under ER stress conditions caused by chronic high glucose. The rapid degradation of insulin mRNA could provide immediate relief for the ER and free up the translocation machinery. Thus, this mechanism would preserve ER homeostasis and help ensure that the insulin already inside the ER can be properly folded and secreted. This adaptation may be crucial for the maintenance of β-cell homeostasis and may explain why the β-cells of type 2 diabetic patients with chronic hyperglycemia stop producing insulin in the absence of apoptosis. This mechanism may also be involved in suppression of the autoimmune type 1 diabetes by reducing the amount of misfolded insulin, which could be a source of “neo-autoantigens.

A novel small molecule inhibitor of MRCK prevents radiation-driven invasion in glioblastoma

Glioblastoma (GBM) is an aggressive and incurable primary brain tumor that causes severe neurological, cognitive, and psychological symptoms. Symptoms are caused and exacerbated by the infiltrative properties of GBM cells, which enable them to pervade the healthy brain and disrupt normal function. Recent research has indicated that, while radiotherapy (RT) remains the most effective component of multimodality therapy for GBM patients, it can provoke a more infiltrative phenotype in GBM cells that survive treatment. Here we demonstrate an essential role of the actin-myosin regulatory kinase myotonic dystrophy kinase-related CDC42- binding kinase (MRCK) in mediating the pro-invasive effects of radiation. MRCK-mediated invasion occurred via downstream signaling to effector molecules MYPT1 and MLC2. MRCK was activated by clinically relevant doses per fraction of radiation, and this activation was concomitant with an increase in GBM cell motility and invasion. Furthermore, ablation of MRCK activity either by RNAi or by inhibition with the novel small molecule inhibitor BDP-9066 prevented radiation-driven increases in motility both in vitro and in a clinically relevant orthotopic xenograft model of GBM. Crucially, treatment with BDP-9066 in combination with RT significantly increased survival in this model and markedly reduced infiltration of the contralateral cerebral hemisphere

Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis

The compliance and dimensionality of the ECM regulate distinct changes in microtubule growth speed and growth persistence

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Differential Gene Expression in the EphA4 Knockout Spinal Cord and Analysis of the Inflammatory Response Following Spinal Cord Injury

Mice lacking the axon guidance molecule EphA4 have been shown to exhibit extensive axonal regeneration and functional recovery following spinal cord injury. To assess mechanisms by which EphA4 may modify the response to neural injury a microarray was performed on spinal cord tissue from mice with spinal cord injury and sham injured controls. RNA was purified from spinal cords of adult EphA4 knockout and wild-type mice four days following lumbar spinal cord hemisection or laminectomy only and was hybridised to Affymetrix All-Exon Array 1.0 GeneChips™. While subsequent analyses indicated that several pathways were altered in EphA4 knockout mice, of particular interest was the attenuated expression of a number of inflammatory genes, including Arginase 1, expression of which was lower in injured EphA4 knockout compared to wild-type mice. Immunohistological analyses of different cellular components of the immune response were then performed in injured EphA4 knockout and wildtype spinal cords. While numbers of infiltrating CD3+ T cells were low in the hemisection model, a robust CD11b+ macrophage/microglial response was observed post-injury. There was no difference in the overall number or spread of macrophages/activated microglia in injured EphA4 knockout compared to wild-type spinal cords at 2, 4 or 14 days post-injury, however a lower proportion of Arginase-1 immunoreactive macrophages/activated microglia was observed in EphA4 knockout spinal cords at 4 days post-injury. Subtle alterations in the neuroinflammatory response in injured EphA4 knockout spinal cords may contribute to the regeneration and recovery observed in these mice following injury