The effects of estrogen and testosterone on gene expression in the rat mesenteric arteries.

A dramatic difference exists in the timing of development of cardiovascular disease in men vs. women. The primary candidates underlying the cause of this gender difference are the sex steroids, estrogen and testosterone. The vasculature is considered to be a site of action of these steroids. In spite of these concepts there is little data on the direct effects of estrogen and testosterone on gene expression in the vasculature. In this study, ovariectomized Sprague Dawley rats were treated for 4 days with vehicle (sesame oil), estradiol benzoate (0.15 mg/kg/day), or testosterone (1 mg/kg/day). The mesenteric arteries were obtained, total RNA was extracted, and CodeLink Uniset Rat I DNA microarrays were used to identify differential gene expression. Seven genes were identified as differentially expressed from the DNA microarray data and confirmed by real time RT-PCR. The expression of D site albumin promoter binding protein and fatty acid synthase were increased in response to both estrogen and testosterone. 3 alpha-hydroxysteroid dehydrogenase, interleukin 4 receptor, JunB and c-Fos expression were increased by estrogen but not by testosterone. Aryl hydrocarbon nuclear translocator-like gene was reduced by testosterone. These data identify genes not previously known to be responsive to estrogen and testosterone in the vasculature.

Inviting the public: the impact on informatics arising from emerging global health research paradigms.

This workshop will focus on disruptive processes impacting research arising from the increasing ability of individuals to create, curate and share data with scientists. Encompassing processes from funding research to providing samples to creating algorithms, including the public will require new approaches even as it opens up new possibilities. We will hear from a few researchers at the forefront of these disruptive processes, followed by a moderated discussion with the audience about these topics.

Postural-stability tests that identify individuals with chronic ankle instability.

CONTEXT: Chronic ankle instability (CAI) is characterized by repeated ankle sprains, which have been linked to postural instability. Therefore, it is important for clinicians to identify individuals with CAI who can benefit from rehabilitation. OBJECTIVE: To assess the likelihood that CAI participants will exhibit impaired postural stability and that healthy control participants will exhibit better test performance values. DESIGN: Case-control study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: People with CAI (n = 17, age = 23 ± 4 years, height = 168 ± 9 cm, weight = 68 ± 12 kg) who reported ankle "giving-way" sensations and healthy volunteers (n = 17, age = 23 ± 3 years, height = 168 ± 8 cm, weight = 66 ± 12 kg). INTERVENTION(S): Participants performed 7 balance tests: Balance Error Scoring System (BESS), time in balance, foot lift, single-legged stance on a force plate, Star Excursion Balance Test, side hop, and figure-of-8 hop. MAIN OUTCOME MEASURE(S): Balance was quantified with errors (score) for the BESS, length of time balancing (seconds) for time-in-balance test, frequency of foot lifts (score) for foot-lift test, velocity (cm/s) for all center-of-pressure velocity measures, excursion (cm) for center-of-pressure excursion measures, area (cm2) for 95% confidence ellipse center-of-pressure area and center-of-pressure rectangular area, time (seconds) for anterior-posterior and medial-lateral time-to-boundary (TTB) measures, distance reached (cm) for Star Excursion Balance Test, and time (seconds) to complete side-hop and figure-of-8 hop tests. We calculated area-under-the-curve values and cutoff scores and used the odds ratio to determine if those with and without CAI could be distinguished using cutoff scores. RESULTS: We found significant area-under-the-curve values for 4 static noninstrumented measures, 3 force-plate measures, and 3 functional measures. Significant cutoff scores were noted for the time-in-balance test (≤25.89 seconds), foot-lift test (≥5), single-legged stance on the firm surface (≥3 errors) and total (≥14 errors) on the BESS, center-of-pressure resultant velocity (≥1.56 cm/s), standard deviations for medial-lateral (≤1.56 seconds) time-to-boundary and anterior-posterior (≤3.78 seconds) time-to-boundary test, posteromedial direction on the Star Excursion Balance Test (≤0.91), side-hop test (≥12.88 seconds), and figure-of-8 hop test (≥17.36 seconds). CONCLUSIONS: Clinicians can use any of the 10 significant measures with their associated cutoff scores to identify those who could benefit from rehabilitation that reestablishes postural stability.

A preliminary and comparative evaluation of a novel Ad5 [E1-, E2b-] recombinant-based vaccine used to induce cell mediated immune responses.

Adenovirus vectors have been shown to be highly effective as vaccine platforms capable of inducing both humoral and cell mediated immune (CMI) responses. An Ad serotype 5 vector containing unique deletions in the E2b region (Ad5 [E1-, E2b-]) has been reported to have several advantages over conventional Adenovirus serotype 5 (Ad5) vectors deleted in only the E1 region (Ad5 [E1-]), including increased carrying capacity and diminished viral late gene expression. Here, we evaluated a novel Ad5 [E1-, E2b-] vector utilizing the E.C7 cell line for viral packaging. Its' effectiveness as a potential vaccine platform as compared to the currently utilized Ad5 [E1-]-based platform was assessed in both Ad5 naïve and Ad5 immune mice. We employed the HIV-1 Gag gene as the antigenic transgene expressed by the novel vector. Cellular expression of the Gag was confirmed by Western Blot analysis. Dose response studies using three intradermal immunizations of 10(7) to 10(10) virus particles (VP) of each construct revealed that immunization with 10(10)VP resulted in the maximum immunological response. Multiple immunizations of Ad naïve BALB/c mice with an Ad5 [E1-, E2b]-gag vaccine resulted in higher ELISpot CMI responses as compared to mice immunized with an Ad5 [E1-]-gag vaccine. More importantly, multiple immunizations of Ad5 immune BALB/c mice with an Ad5 [E1-, E2b]-gag vaccine resulted in significant increases in ELISpot CMI responses when compared to Ad5 immune mice vaccinated with an Ad5 [E1-]-gag vector. Preliminary studies in three Ad5 immune non-human primates (NHP) demonstrated that vaccination with Ad5 [E1-, E2b-]-gag-induced elevated levels of interferon-gamma and IL-2 secreting lymphocytes as assessed by ELISpot assays. These studies indicate that the novel Ad5 [E1-, E2b-] viral vector can be utilized as a potential vaccine platform to induce elevated CMI responses as compared to current generation Ad5 [E1-] viral vectors even in the presence of pre-existing Ad5 immunity.