DNA array analysis of interleukin-2-regulated immediate/early genes

BACKGROUND: Lymphocyte activation culminates in blastogenesis, cell cycle progression, DNA replication and mitosis. These complex cellular changes are programmed almost simultaneously by multiple ligands and receptors that trigger specific signal transduction pathways and transcription factors. Until now, the discovery of the genes regulated by each ligand/receptor pair has been hampered by the technologies available. RESULTS: To identify interleukin-2 (IL-2)-responsive genes, human peripheral blood mononuclear cells (PBMC) were pre-activated with anti-CD3, rested, and restimulated with IL-2 for 4 hr. Gene expression was analyzed using Affymetrix U95Av2 oligonucleotide arrays. To determine the most stringent parameters to score a gene as a bona fide IL-2 target, the expression of 19 known IL-2-regulated genes was examined first. All were induced at least 2-fold, with a difference in fluorescent intensity of ≥ 100 at p < 0.05. An additional 53 unique genes met these criteria. To determine which of these were immediate/early IL-2 targets in T cells, purified T cells were stimulated with IL-2 for 4 hr in the presence of cycloheximide to prevent secondary gene expression. Of the 72 genes identified in PBMCs, 20 were detected as immediate/early IL-2-regulated genes in purified T cells. In addition, 27 unique genes were IL-2-regulated in T cells but not in PBMCs. CONCLUSIONS: For a successful reductionist approach to the analysis of gene expression in lymphocyte activation, it is necessary to examine purified cell populations and immediate/early gene expression regulated by each ligand/receptor pair involved. This approach should allow the discovery of genes regulated by all of the ligand/receptor pairs involved in lymphocyte activation

Information-theoretic classification of SNOMED improves the organization of context-sensitive excerpts from Cochrane Reviews

The emphasis on evidence based medicine (EBM) has placed increased focus on finding timely answers to clinical questions in presence of patients. Using a combination of natural language processing for the generation of clinical excerpts and information theoretic distance based clustering, we evaluated multiple approaches for the efficient presentation of context-sensitive EBM excerpts

NEW AND UPDATED RECORDS FOR AMPHIBIANS AND REPTILES IN MINNESOTA, USA

Following the publication of the revised edition of “Amphibians and Reptiles in Minnesota” by Moriarty and Hall (2014), we accessioned several new or updated records at the Bell Museum of Natural History (JFBM). Records include digital photographs (accession number preceded by “P”) and audio recordings (accession number preceded by “AUD”). In addition, a subset of these observations were accessioned in www.HerpMapper.org. HerpMapper accession numbers are preceded by “HM” and can be viewed online. Benjamin Lowe verified species determinations. Latitude and longitude coordinates are based on datum WGS 84

Expression of a human cartilage procollagen gene (COL2A1) in mouse 3T3 cells.

Expression in a recombinant system has been difficult to obtain for any of the major fibrillar collagens that require processing by eight or more post-translational enzymes. Here, two DNA constructs were designed so that the promoter region of the gene for the pro-alpha 1(I) chain of human type I procollagen drove expression of the human type II procollagen gene in mouse NIH 3T3 cells, a culture line that normally synthesizes type I procollagen but not any cartilage-specific protein such as type II procollagen. Both constructs were expressed as both mRNA and protein. In clones expressing the construct at high levels, the steady-state levels of mRNA and the production of type II procollagen were comparable to the mRNA levels and production of type I procollagen from the endogenous mouse genes. Comparison of clones containing the two constructs demonstrated that sequences extending 80 base pairs beyond the major polyadenylation signal of the gene are not in themselves sufficient for correct termination and 3\u27 processing of RNA transcripts. The results strongly suggest that specific sequences present in a downstream 3.5-kilobase SphI/SphI fragment determine the termination of the transcription. Of special importance is that the system will make it possible to examine the consequences of mutations in the human type II procollagen gene on the processing of RNA transcripts and on the functional properties of the protein simply by using the genomic DNA from leukocytes or other non-cartilaginous sources

Helping Teachers Develop Positive Dispositions about Technology-based Learning: What a Brief Global Learning Project Revealed

Research indicates that teachers’ dispositions significantly influence their integration of computer technology into classroom instruction. This article reports findings from a mixed-methods study that examined shifts in teachers’ dispositions about learning that occurs through information and communication technologies (ICT’s). Graduate students and remote professionals engaged in a one-semester learning project that included synchronous and asynchronous com­puter-mediated discussions of course content. The study sought to determine whether or not this exposure to ICT-based learning might be accompanied by a positive or negative affective shift, and to identify the salient features of such a shift. Quantitative analysis of responses on question­naires administered early and late in the semester revealed a statistically significant positive shift in participants’ beliefs and dispositions regarding ICT-based learning. Qualitative analysis of the questionnaire responses and participants’ digital discussions identified two salient features of that positive shift in that participants recognized the potential of ICT-based learning to 1) motivate and engage learners, and 2) facilitate the construction and sharing of new knowledge and understand­ing. This paper describes the study and considers the implications for teacher preparation and professional development

Road safety education for older drivers : evaluation of a classroom-based training initiative

Around the world, a growing proportion of drivers are aged 70 or over. Although accident rates for older drivers are lower than for young or novice drivers, increased frailty and slowed reactions mean that older drivers are at higher risk of death or serious injury when involved in a road collision. The objectives of this study were to: (a) identify driving knowledge and self-regulatory strategies among a group of older drivers with a view to planning future on-road training; (b) measure driver self-assessments of ability and confidence before and after classroom training delivered by driving instructors; (c) evaluate the utility and acceptability of training courses for older drivers using questionnaires and focus groups; d) examine the characteristics of course participants. 142 drivers aged ≥75 completed a two-hour classroom-based driving course and took part in the evaluation: 94 aged 75–79, 48 aged ≥80, 68% male. Main reasons for taking part were to update knowledge, improve driving and check they were safe to drive. Results showed that females were more likely than males to avoid driving in difficult conditions (at night, in bad weather, unfamiliar roads). More drivers aged 75–79 said they did not restrict their driving (52, 57%) compared to drivers aged ≥80 (19, 43%). Pre-course, males rated their driving confidence and ability significantly higher than females. Post-course, self-ratings of confidence and ability were unchanged for 76 (60%) drivers. However, two-thirds reported improved knowledge and 80% said they would change their driving behaviour as a result of the course. Focus group results suggest that competent drivers are more likely to attend educational courses than unsafe drivers. This study provides preliminary evidence that classroom-based training can initiate behaviour change among older drivers. Future research will examine the effectiveness of on-road training in this age group

Genetic Markers as Instrumental Variables

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from epidemiologists, economists, statisticians and social scientists. This paper examines the conditions that need to be met for genetic variants to be used as instruments. Although these have been discussed in the epidemiological, medical and statistical literature, they have not been well-defined in the economics and social science literature. The increasing availability of biomedical data however, makes understanding of these conditions crucial to the successful use of genotypes as instruments for modifiable risk factors. We combine the econometric IV literature with that from genetic epidemiology using a potential outcomes framework and review the IV conditions in the context of a social science application, examining the effect of child fat mass on academic performance.ALSPAC; Fat mass; Genetic Variants; Instrumental Variables; Mendelian Randomization; Potential Outcomes

Genetic Markers as Instrumental Variables:An Application to Child Fat Mass and Academic Achievement

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from economists. This paper examines the conditions that need to be met for genetic variants to be used as instruments. We combine the IV literature with that from genetic epidemiology, with an application to child adiposity (fat mass, determined by a dual-energy X-ray absorptiometry (DXA) scan) and academic performance. OLS results indicate that leaner children perform slightly better in school tests compared to their more adipose counterparts, but the IV findings show no evidence that fat mass affects academic outcomes.Instrumental variables; Mendelian randomization; Genetic variant; Potential outcomes; Academic performance; Educational attainment; Adiposity; Fat mass; Body Mass Index; ALSPAC

Child height, health and human capital: evidence using genetic markers

Height has long been recognised as associated with better outcomes: the question is whether this association is causal. We use children’s genetic variants as instrumental variables (IV) to deal with possible unobserved confounders and examine the effect of child and adolescent height on a wide range of outcomes: academic performance, IQ, self-esteem, symptoms related to depression and behavioural problems, including hyperactivity, emotional, conduct and peer problems. OLS findings show that taller children have higher IQ scores, perform better in school tests, and are less likely to have emotional or peer problems. The IV results differ. They show that taller children have better cognitive performance but, in contrast to the OLS, indicate that taller children are more likely to have behavioural problems. The magnitude of these IV estimates is large. For example, the effect of one standard deviation increase in height on IQ is comparable to the IQ difference for children born approximately 6 months apart within the same school year, while the increase in hyperactivity is comparable to the raw difference in hyperactivity between boys and girls.Child and adolescent height; human capital; mental health; behavioural outcomes; instrumental variables; Mendelian randomization; genetic variants; ALSPAC

Genetic markers as instrumental variables: an application to child fat mass and academic achievement

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from economists. This paper examines the conditions that need to be met for genetic variants to be used as instruments. We combine the IV literature with that from genetic epidemiology, with an application to child adiposity (fat mass, determined by a dual-energy X-ray absorptiometry (DXA) scan) and academic performance. OLS results indicate that leaner children perform slightly better in school tests compared to their more adipose counterparts, but the IV findings show no evidence that fat mass affects academic outcomes.