Tn5/IS50 target recognition

This communication reports an analysis of Tn5/IS50 target site selection by using an extensive collection of Tn5 and IS50 insertions in two relatively small regions of DNA (less than 1 kb each). For both regions data were collected resulting from in vitro and in vivo transposition events. Since the data sets are consistent and transposase was the only protein present in vitro, this demonstrates that target selection is a property of only transposase. There appear to be two factors governing target selection. A target consensus sequence, which presumably reflects the target selection of individual pairs of Tn5/IS50 bound transposase protomers, was deduced by analyzing all insertion sites. The consensus Tn5/IS50 target site is A-GNTYWRANC-T. However, we observed that independent insertion sites tend to form groups of closely located insertions (clusters), and insertions very often were spaced in a 5-bp periodic fashion. This suggests that Tn5/IS50 target selection is facilitated by more than two transposase protomers binding to the DNA, and, thus, for a site to be a good target, the overlapping neighboring DNA should be a good target, too. Synthetic target sequences were designed and used to test and confirm this model.

Randomised controlled trial comparing effectiveness and acceptability of an early discharge, hospital at home scheme with acute hospital care

Objective: To compare effectiveness and acceptability of early discharge to a hospital at home scheme with that of routine discharge from acute hospital.

Hospital at home or acute hospital care? A cost minimisation analysis

Objective: To compare, from the viewpoints of the NHS and social services and of patients, the costs associated with early discharge to a hospital at home scheme and those associated with continued care in an acute hospital.

Deletion of cytosolic phospholipase A2 suppresses ApcMin-induced tumorigenesis

Although nonsteroidal antiinflammatory drugs (NSAIDs) show great promise as therapies for colon cancer, a dispute remains regarding their mechanism of action. NSAIDs are known to inhibit cyclooxygenase (COX) enzymes, which convert arachidonic acid (AA) to prostaglandins (PGs). Therefore, NSAIDs may suppress tumorigenesis by inhibiting PG synthesis. However, various experimental studies have suggested the possibility of PG-independent mechanisms. Notably, disruption of the mouse group IIA secretory phospholipase A2 locus (Pla2g2a), a potential source of AA for COX-2, increases tumor number despite the fact that the mutation has been predicted to decrease PG production. Some authors have attempted to reconcile the results by suggesting that the level of the precursor (AA), not the products (PGs), is the critical factor. To clarify the role of AA in tumorigenesis, we have examined the effect of deleting the group IV cytosolic phospholipase A2 (cPLA2) locus (Pla2g4). We report that ApcMin/+, cPLA2−/− mice show an 83% reduction in tumor number in the small intestine compared with littermates with genotypes ApcMin/+, cPLA2+/− and ApcMin/+, cPLA2+/+. This tumor phenotype parallels that of COX-2 knockout mice, suggesting that cPLA2 is the predominant source of AA for COX-2 in the intestine. The protective effect of cPLA2 deletion is thus most likely attributed to a decrease in the AA supply to COX-2 and a resultant decrease in PG synthesis. The tumorigenic effect of sPLA2 mutations is likely to be through a completely different pathway.

FGF-2 regulation of neurogenesis in adult hippocampus after brain injury

Fibroblast growth factor-2 (FGF-2) promotes proliferation of neuroprogenitor cells in culture and is up-regulated within brain after injury. Using mice genetically deficient in FGF-2 (FGF-2−/− mice), we addressed the importance of endogenously generated FGF-2 on neurogenesis within the hippocampus, a structure involved in spatial, declarative, and contextual memory, after seizures or ischemic injury. BrdUrd incorporation was used to mark dividing neuroprogenitor cells and NeuN expression to monitor their differentiation into neurons. In the wild-type strain, hippocampal FGF-2 increased after either kainic acid injection or middle cerebral artery occlusion, and the numbers of BrdUrd/NeuN-positive cells significantly increased on days 9 and 16 as compared with the controls. In FGF-2−/− mice, BrdUrd labeling was attenuated after kainic acid or middle cerebral artery occlusion, as was the number of neural cells colabeled with both BrdUrd and NeuN. After FGF-2−/− mice were injected intraventricularly with a herpes simplex virus-1 amplicon vector carrying FGF-2 gene, the number of BrdUrd-labeled cells increased significantly to values equivalent to wild-type littermates after kainate seizures. These results indicate that endogenously synthesized FGF-2 is necessary and sufficient to stimulate proliferation and differentiation of neuroprogenitor cells in the adult hippocampus after brain insult.

A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice.

Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection. When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice developed a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth. The disease was characterized by erythema, hair loss, and the development of scales and crusts. The histopathology revealed hyperplasia of the epidermis, subcorneal microabscesses, orthohyperkeratosis, parakeratosis, and lymphocyte exocytosis, which are features in common with human psoriasis and other hyperproliferative inflammatory skin disorders. Repetitive cultures failed to demonstrate bacterial or fungal organisms potentially involved in the pathogenesis of this disease, and the dermatitis resolved rapidly after subcutaneous administration of dexamethasone. Homozygous mutant mice on a (PL/J x C57BL/6J)F1 background did not develop the disease and backcross experiments suggest that a small number of genes (perhaps as few as one), in addition to CD18, determine susceptibility to the disorder. This phenotype provides a model for inflammatory skin disorders, may have general relevance to polygenic human inflammatory diseases, and should help to identify genes that interact with the beta2 integrins in inflammatory processes.

Got A Minute: Instruction Tune-Up for Time Pressed Librarians

This book contains 19 essays that have been written by current LIS Students who were enrolled in the LIS4330: Library Instruction class at the University of Denver, 2016. Designed to provide a short and pithy overview of a topic that is related to instruction, education, or information literacy, each essays aims to be accessible and approachable for time-pressed librarians who may not have time to catch up.

Una perspectiva del Banco Mundial

El Banco Mundial aporta cualidades características al papel que puede desempeñar en promover la transición del ámbito humanitario al del desarrollo y está aumentando de manera significativa su compromiso con el desplazamiento forzado.

Perspectives of Teachers Regarding the Integration of Mathematics and Science at the Secondary School Level

The integration of mathematics and science in secondary schools in the 21st century continues to be an important topic of practice and research. The purpose of my research study, which builds on studies by Frykholm and Glasson (2005) and Berlin and White (2010), is to explore the potential constraints and benefits of integrating mathematics and science in Ontario secondary schools based on the perspectives of in-service and pre-service teachers with various math and/or science backgrounds. A qualitative and quantitative research design with an exploratory approach was used. The qualitative data was collected from a sample of 12 in-service teachers with various math and/or science backgrounds recruited from two school boards in Eastern Ontario. The quantitative and some qualitative data was collected from a sample of 81 pre-service teachers from the Queen’s University Bachelor of Education (B.Ed) program. Semi-structured interviews were conducted with the in-service teachers while a survey and a focus group was conducted with the pre-service teachers. Once the data was collected, the qualitative data were abductively analyzed. For the quantitative data, descriptive and inferential statistics (one-way ANOVAs and Pearson Chi Square analyses) were calculated to examine perspectives of teachers regardless of teaching background and to compare groups of teachers based on teaching background. The findings of this study suggest that in-service and pre-service teachers have a positive attitude towards the integration of math and science and view it as valuable to student learning and success. The pre-service teachers viewed the integration as easy and did not express concerns to this integration. On the other hand, the in-service teachers highlighted concerns and challenges such as resources, scheduling, and time constraints. My results illustrate when teachers perceive it is valuable to integrate math and science and which aspects of the classroom benefit best from the integration. Furthermore, the results highlight barriers and possible solutions to better the integration of math and science. In addition to the benefits and constraints of integration, my results illustrate why some teachers may opt out of integrating math and science and the different strategies teachers have incorporated to integrate math and science in their classroom.

Energizing the Oak Ridges Moraine? Analyzing the Policy Implications of Three Wind Energy Developments on the Oak Ridges Moraine and their Potential Impact on the Coordinated Land Use Planning Review through the Involvement of First Nations and Environmental Non-governmental Organizations

This research explores the policy implications of the approval of three wind energy projects on the Oak Ridges Moraine, and their impact on the Coordinated Land Use Planning Review process. Specifically, it focuses on the involvement of First Nations and environmental non-governmental organizations (ENGOs). This research was conducted through analyzing submissions to the Coordinated Land Use Planning Review, related legislation and policy, Environmental Review Tribunal hearing documents, and interviews with key informants. This research culminates in a number of recommendations to the Coordinated Review informed by the analysis.