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Biomedical subjects

E Fox

Publications and source records attributed to E Fox.

At least 37 records · Page 2Linked to original sources

SDQR migrations in Caenorhabditis elegans are controlled by multiple guidance cues and changing responses to netrin UNC-6.

The netrin guidance cue, UNC-6, and the netrin receptors, UNC-5 and UNC-40, guide SDQR cell and axon migrations in C. elegans. In wild-type larvae, SDQR migrations are away from ventral UNC-6-expressing cells, suggesting that UNC-6 repels SDQR. In unc-6 null larvae, SDQR migrations are towards the ventral midline, indicating a response to other guidance cues that directs the migrations ventrally. Although ectopic UNC-6 expression dorsal to the SDQR cell body would be predicted to cause ventral SDQR migrations in unc-6 null larvae, in fact, more migrations are directed dorsally, suggesting that SDQR is not always repelled from the dorsal source of UNC-6. UNC-5 is required for dorsal SDQR migrations, but not for the ventral migrations in unc-6 null larvae. UNC-40 appears to moderate both the response to UNC-6 and to the other cues. Our results show that SDQR responds to multiple guidance cues and they suggest that, besides UNC-6, other factors influence whether an UNC-6 responsive cell migrates toward or away from an UNC-6 source in vivo. We propose that multiple signals elicited by the guidance cues are integrated and interpreted by SDQR and that the response to UNC-6 can change depending on the combination of cues encountered during migration. These responses determine the final dorsoventral position of the SDQR cell and axon.

Animals↗

Quantitative RT-PCR to evaluate in vivo expression of multiple transgenes using a common intron.

An assay measuring RNA expression levels of a gene-encoded therapeutic must distinguish between endogenous mRNA and mRNA transcribed from the transgene. Specificity for the delivered transgene is especially critical when the treatment involves genes that are expressed in the target tissue. To facilitate uniform detection of transgene RNA without interference from endogenous mRNA, we have engineered expression vectors that include a 5' untranslated region (5' UTR) containing a synthetic intron (PGL3). The synthetic intron splice junction was the target sequence for a quantitative reverse transcription (RT)-PCR assay utilizing Taq-Man technology. In this study, we demonstrate that a quantitative RT-PCR assay designed to recognize an engineered intron splice site in the 5'UTR of expression constructs effectively measures the expression level of in vivo-delivered gene therapeutics.

5' Untranslated Regions↗

Parasite density and malaria morbidity in the Pakistani Punjab.

The relationship between quantitative Plasmodiumfalciparum or P. vivax parasitemia and clinical illness has not been defined in Pakistan or in other areas where malaria transmission is not highly endemic. Standardized questionnaires were given to and physical examinations and parasitologic tests were performed in 8,941 subjects seen in outpatient clinics in 4 villages for 13 consecutive months in the Punjab region of Pakistan. The results, based on multivariable analysis, showed that a clinical diagnosis of malaria, a history of fever, rigors, headache, myalgia, elevated temperature, and a palpable spleen among children were all strongly associated with the presence and density of P. falciparum or P. vivax malaria in a monotonic dose-response fashion. The malaria attributable fraction of a clinical diagnosis of malaria, and the same symptoms and signs also increased with increasing P. falciparum and, to a lesser extent, P. vivax, parasitemia. Unlike in sub-Saharan Africa, clinical illness due to malaria often occurs in the Punjab among adolescents and adults and in patients with parasite densities less than 1,000/microl. Clinical guidelines based upon parasitemia and symptomatology must be adjusted according to the intensity of transmission and be specific for each geographic area.

Adolescent↗

Role of netrin UNC-6 in patterning the longitudinal nerves of Caenorhabditis elegans.

The nervous system of Caenorhabditis elegans comprises circumferential and longitudinal axon tracts. Netrin UNC-6 is required for the guidance of circumferential axon migrations and is expressed by ventral neuroglia and neurons in temporally and spatially regulated patterns. Migrating axons mediate the UNC-6 signal through the UNC-5 and UNC-40 receptors. It is thought that UNC-6 is secreted and becomes associated with basement membranes and cell surfaces to form gradients that direct circumferentially migrating axons toward or away from the ventral UNC-6 sources. Little is known about the effects of UNC-6 on longitudinally migrating axons. In unc-6, unc-5, and unc-40 null mutants, some longitudinal nerves are dorsally or ventrally misdirected. Furthermore, the organization of axons are disrupted within nerves. We show that cells ectopically expressing UNC-6 can redirect the migrations of some neighboring longitudinal axons, suggesting that the gradients postulated to direct circumferential migration also help specify the dorsoventral positions of these longitudinal nerves. We also manipulated the temporal and spatial expression pattern of UNC-6 by two different means. First, we removed the PVT midline neuron which expresses UNC-6 for a short time during axon outgrowths. Second, we expressed UNC-6 uniformly in the nervous system throughout development. The results suggest that changing UNC-6 expression patterns modify the distribution of the cue by providing new localized sources. This new guidance information is critical for organizing the axons of longitudinal nerves.

Animals↗

Perceptual grouping and visual selective attention.

The present study demonstrates that incongruent distractor letters at a constant distance from a target letter produce more response competition and negative priming when they share a target's color than when they have a different color. Moreover, perceptual grouping by means of color, attenuated the effects of spatial proximity. For example, when all items were presented in the same color, near distractors produced more response competition and negative priming than far distractors (Experiment 3A). However, when near distractors were presented in a different color and far distractors were presented in the same color as the target, the response competition x distractor proximity interaction was eliminated and the proximity x negative priming interaction was reversed (Experiment 3B). A final experiment demonstrated that distractors appearing on the same object as a selected target produced comparable amounts of response competition and negative priming whether they were near or far from the target. This suggests that the inhibitory mechanisms of visual attention can be directed to perceptual groups/objects in the environment and not only to unsegmented regions of visual space.

Adolescent↗

Efficient in vivo delivery of DNA to pulmonary cells using the novel lipid EDMPC.

We compared the efficacy of gene transfer in vitro and in vivo using various formulations of DNA-lipid complexes based on the novel cationic lipid EDMPC (1,2-dimyristoylsn-glycero-3-ethylphosphocholine, chloride salt). In vitro studies analyzed delivery of marker genes to four established cell lines, including two of pulmonary origin. The in vivo analysis used intralobar delivery of marker genes and CFTR to mice and rats. We observed a lack of positive correlation between those DNA-EDMPC formulations that delivered DNA most efficiently in vitro and those that worked best in vivo. Intralobar DNA delivery to rodents mediated by EDMPC was efficient. The high level of gene delivery by DNA-EDMPC formulations demonstrates that efficient lipid-mediated gene transfer to the lung is possible.

Animals↗

Phimosis.

Explore the source record for details and available documents.

Adult↗

District nursing associations and doctors: aspects of interprofessional relationships, 1902-1914.

District nursing associations' midwifery was the key to their early twentieth-century growth, which would have been impossible without doctors' co-operation. Yet doctors were reportedly hostile to district nurses in this period, and had particular reasons for resisting their midwifery. Here it is argued that the Queen's Institute's co-ordination of the associations' work, and its conduct of negotiations with the British Medical Association, promoted arrangements under which doctors were likely to gain more than they feared losing by accepting district nurses' midwifery.

History, 20th Century↗

Concepts in evaluation applied to ethics consultation research.

Planning evaluative research requires a number of essential tasks. First, it is important to consider the underlying purpose of the evaluative effort. Next, research questions must be carefully defined. Specifically, evaluative research might examine questions of quality (including structure, process, and outcomes), access, or efficiency. Additional tasks include the enumeration of variables of interest, the selection of appropriate data collection techniques, and the creation of reliable and valid instruments. Finally, a study's research design should suit the goals of the investigation. The tasks outlined in this conceptual framework are all prerequisite to rigorous evaluative research.

Cost-Benefit Analysis↗