Science in a shifting policy system.

In June, the US Supreme Court overturned a 40-yearold legal principle known as the doctrine, which deferred to federal agencies on how regulations are interpreted in legal cases when the legislation enacted by Congress is unclear. Striking a blow against this precedent, Supreme Court Chief Justice John Roberts indicated that was "fundamentally misguided" and that only the nation's courts have the prerogative to interpret the laws they administer. Judges across the United States now anticipate an onslaught of litigation seeking to overturn federal regulatory actions, and many of these lawsuits will turn on scientific evidence that guided those actions.

Sexual and Gender Minority Health Research at the National Institutes of Health.

Sexual and gender minority (SGM) populations experience many diseases and conditions at higher prevalence rates than their non-SGM counterparts. In 2009, the National Institutes of Health (NIH) commissioned an Institute of Medicine (IOM) report to better understand the health of SGM populations. Following the release of the report, NIH, including the National Cancer Institute (NCI), initiated new activities, and continued and expanded its existing efforts to advance the health of SGM individuals.

Humoral immune responses to HIV in the mucosal secretions and sera of HIV-infected women.

Although sera and all external secretions contain antibodies to human immunodeficiency virus (HIV), their levels, specificity, isotypes, and relevant effector functions display a great degree of variability. Antibodies that bind HIV antigens and neutralize the virus are predominantly associated with the IgG isotype in sera and in all external secretions, even where total levels of IgG are much lower than those of IgA. Rectal fluid that contains high IgA, but low IgG levels, displayed low neutralizing activity independent of antibodies.

Comparative Evaluation of HIV-1 Neutralization in External Secretions and Sera of HIV-1-Infected Women.

Objectives: Although human immunodeficiency virus type 1 (HIV-1)-specific antibodies are detectable in external secretions by ELISA and western blot (WB), the presence of HIV-1 neutralizing antibodies is difficult to evaluate due to the low levels of immunoglobulins (Ig) and the presence of humoral factors of innate immunity. The objective of this study was to determine virus neutralization activity and the relative contribution of HIV-1-specific antibodies of various isotypes to virus neutralization in serum/plasma samples, cervicovaginal lavages (CVL), and rectal lavages (RL).

Design: Serum/plasma, CVL, and RL samples were examined by ELISA, WB and HIV-1 neutralization assays.

Scarcity or absence of humoral immune responses in the plasma and cervicovaginal lavage fluids of heavily HIV-1-exposed but persistently seronegative women.

To address an existing controversy concerning the presence of HIV-1-specific antibodies of the IgA isotype in the female genital tract secretions of highly-exposed but persistently seronegative (HEPSN) women, 41 samples of plasma and cervicovaginal lavage (CVL) fluid were distributed to six laboratories for their blinded evaluation using ELISA with 10 different HIV-1 antigens, chemiluminescence-enhanced Western blots (ECL-WB), and virus neutralization. HIV-specific IgG or IgA antibodies in plasma samples from HEPSN women were absent or detectable only at low levels. In CVL, 11/41 samples displayed low levels of reactivity in ELISA against certain antigens.

Methods for evaluation of humoral immune responses in human genital tract secretions.

The compilation of epidemiological, virological, and immunological data clearly indicates that HIV-1 infection must be considered primarily as a disease of the mucosal immune system. The earliest and most dramatic alterations of the immune system occur in the mucosal compartment. However, the mucosal immune systems of the genital and intestinal tracts display remarkable immunological differences that must be considered in the evaluation of humoral immune responses in HIV-1-infected individuals or in volunteers immunized with experimental HIV vaccines.

Antibody-mediated protection and the mucosal immune system of the genital tract: relevance to vaccine design.

Mucosal tissues of the genital tracts and the distal intestinal tract are portals of entry for infectious agents of sexually transmitted diseases, including HIV-1. Although the genital and intestinal tracts share a common embryologic origin and remain in anatomical proximity, these two sites display remarkably different immunologic features, including the levels, isotypes and molecular forms of immunoglobulins, and magnitudes and qualities of humoral and cellular immune responses. Thus, viral and bacterial infections of the genital tract or intravaginal immunizations induce, in the absence of mucosal adjuvants, minimal immune responses.

Mucosal immunology of the genital and gastrointestinal tracts and HIV-1 infection.

The male and female genital tracts are protected by a local immune system that displays features distinguishing them from other mucosal sites. In contrast to the intestinal tract, where locally produced IgA is the dominant Ig, secretions of the male and female genital tract contain predominantly IgG of both local and systemic origin. Genital tract tissues also lack mucosal lymphoepithelial inductive sites analogous to intestinal Peyer's patches; consequently, local immunization or infections with sexually transmitted pathogens induce low immune responses.

Neutralizing antibodies in mucosal secretions: IgG or IgA?

The mucosal immune response to HIV weighs in heavily on the battle against it, as the majority of infections occur via the mucosal route. The antibody response in the mucosae, specifically the genital tract, is characterized by binding and, in some studies, neutralizing HIV-specific IgG and IgA antibodies. Ample evidence, however, points to discrepancies and difficulties in the detection of HIV-specific IgA in HIV-positive subjects, and an even more pronounced divide surfaces in studies done with individuals exposed to HIV, but uninfected.

5' transcript replacement in vitro catalyzed by a group I intron-derived ribozyme.

Group I intron-derived ribozymes can perform a variety of catalytic reactions, including the replacement of the 3' end of a mutant RNA transcript with a corrected version of the transcript [Sullenger, B. A., and Cech, T.

Canonical nucleosides can be utilized by T4 DNA ligase as universal template bases at ligation junctions.

T4 DNA ligase catalyzes the template-dependent ligation of DNA. Using T4 DNA ligase under specific experimental conditions, we demonstrate that each of the four canonical nucleosides, centrally located on a template molecule such that they flank the site of ligation, can direct the ligation of nucleic acids regardless of the identity of the terminal nucleosides being covalently joined. This universal templating capability extends to those positions adjacent to the ligation junction.