The NUDGE Framework: Application to Address Behavioral Barriers to Antiretroviral Therapy in Adolescents Living With HIV in Eswatini.

Behavioral economics offers a unique opportunity to understand the social, cognitive, and psychological nuances that may influence health behavior. The purpose of this article is to demonstrate the application of NUDGE, a novel behavioral economics and design thinking framework, to address barriers to antiretroviral therapy adherence among adolescents living with HIV in eSwatini. NUDGE comprises five steps: (1) Narrow the focus to a specific target behavior, (2) Understand the context of the behavior through inquiry, (3) Discover behavioral insights related to the target behavior, (4) Generate intervention design features to address behavioral barriers to the target behavior, and (5) Evaluate the design features through iterative pilot testing.

The plant response to high CO levels is heritable and orchestrated by DNA methylation.

Plant responses to abiotic environmental challenges are known to have lasting effects on the plant beyond the initial stress exposure. Some of these lasting effects are transgenerational, affecting the next generation. The plant response to elevated carbon dioxide (CO ) levels has been well studied.

An siRNA-guided ARGONAUTE protein directs RNA polymerase V to initiate DNA methylation.

In mammals and plants, cytosine DNA methylation is essential for the epigenetic repression of transposable elements and foreign DNA. In plants, DNA methylation is guided by small interfering RNAs (siRNAs) in a self-reinforcing cycle termed RNA-directed DNA methylation (RdDM). RdDM requires the specialized RNA polymerase V (Pol V), and the key unanswered question is how Pol V is first recruited to new target sites without pre-existing DNA methylation.

histone locus body assembly and function involves multiple interactions.

The histone locus body (HLB) assembles at replication-dependent (RD) histone loci and concentrates factors required for RD histone mRNA biosynthesis. The genome has a single locus comprised of ∼100 copies of a tandemly arrayed 5-kB repeat unit containing one copy of each of the 5 RD histone genes. To determine sequence elements required for HLB formation and histone gene expression, we used transgenic gene arrays containing 12 copies of the histone repeat unit that functionally complement loss of the ∼200 endogenous RD histone genes.

Grafting in cosmetic rhinoplasty.

As rhinoplasty techniques continue to evolve toward structural support and away from purely reductive techniques, the need for sophisticated grafting options will escalate to augment or replace critical support mechanisms of the nose. This will result in improved esthetic outcomes and functional results. We have found that well-planned and executed adjunctive grafting techniques can deliver lasting results with preservation of function and cosmesis.

Sjögren syndrome: a review for the maxillofacial surgeon.

Sjögren syndrome is a multisystemic condition that predominantly involves the salivary and lacrimal glands. Also known as sicca complex, the disease often is underdiagnosed and poorly understood. This article provides a comprehensive review on Sjögren syndrome, with an emphasis on diagnosis and treatment modalities.

Part of the C-terminal tail of the envelope gp41 transmembrane glycoprotein of human immunodeficiency virus type 1 is exposed on the surface of infected cells and is involved in virus-mediated cell fusion.

The C-terminal tail of the gp41 transmembrane glycoprotein of the human immunodeficiency virus type 1 (HIV-1) virion is usually thought to be inside the virion, but it has been shown recently that part of the tail is exposed on the virion exterior. Here, using a panel of antibodies, it was demonstrated that the same part of the tail is exposed on the surface of HIV-1-infected C8166 lymphoblastoid cells and HeLa cells infected with a gp41-expressing vaccinia virus recombinant. Both types of infected cell failed to react with p17 matrix protein-specific IgGs until permeabilized with saponin, confirming the integrity of the plasma membrane.

Interfering vaccine: a novel antiviral that converts a potentially virulent infection into one that is subclinical and immunizing.

Infection with human influenza A virus can reach cataclysmic levels, with 40 or more million deaths arising from the 1918 pandemic. Preventative and therapeutic measures have improved since that time, but new approaches are needed. Here, we describe one such new approach--the interfering vaccine, which has two activities--it prophylactically prevents influenza, and at the same time converts an otherwise lethal infection into one that is avirulent and immunizing.

A region of the C-terminal tail of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 contains a neutralizing epitope: evidence for its exposure on the surface of the virion.

The approximately 150 amino acid C-terminal tail of the gp41 transmembrane glycoprotein of human immunodeficiency virus type 1 (HIV-1) is generally thought to be located inside the virion. However, we show here that both monoclonal IgG and polyclonal epitope-purified IgG specific for the (746)ERDRD(750) epitope that lies within the C-terminal tail neutralized infectious virus. IgG was mapped to the C-terminal tail by its failure to neutralize tail-deleted virus, and by sequencing of antibody-escape mutants.

Different effects of a single amino acid substitution on three adjacent epitopes in the gp41 C-terminal tail of a neutralizing antibody escape mutant of human immunodeficiency virus type 1.

The envelope protein of human immunodeficiency virus type 1 (HIV-1) comprises the outer gp 120 SU domain and the anchoring gp41 TM domain, and the conventional view is that it has a single transmembrane region with the following C-terminal sequence situated entirely within the virion. However, we have recently proposed that the gp41 C-terminal region comprises three transmembrane regions and an external loop structure. Part of this loop is the peptide 731PRGPDRPEGIEEEGGERDRDRS752 that carries three antibody epitopes, 734PDRPEG739, 740IEEE743, and 746ERDRD750.

Immunogenic and antigenic dominance of a nonneutralizing epitope over a highly conserved neutralizing epitope in the gp41 envelope glycoprotein of human immunodeficiency virus type 1: its deletion leads to a strong neutralizing response.

The Kennedy peptide, (731)PRGPDRPEGIEEEGGERDRDRS(752), from the cytoplasmic domain of the gp41 transmembrane envelope glycoprotein of HIV-1 contains a conformationally dependent neutralizing epitope (ERDRD) and a linear nonneutralizing epitope (IEEE). No recognized murine T cell epitope is present. The peptide usually stimulates virus-specific antibody, but this is not always neutralizing.

Intranasal immunization with a plant virus expressing a peptide from HIV-1 gp41 stimulates better mucosal and systemic HIV-1-specific IgA and IgG than oral immunization.

Control of pandemic human immunodeficiency virus type 1 (HIV-1) infection ideally requires specific mucosal immunity to protect the genital regions through which transmission more often occurs. Thus a vaccine that stimulates a disseminated mucosal and systemic protective immune response would be extremely useful. Here we have investigated the ability of a chimeric plant virus, cowpea mosaic virus (CPMV), expressing a 22 amino acid peptide (residues 731-752) of the transmembrane gp41 protein of HIV-1 IIIB (CPMV-HIV/1), to stimulate HIV-1-specific and CPMV-specific mucosal and serum antibody following intranasal or oral immunization together with the widely used mucosal adjuvant, cholera toxin.

The neutralizing antibody response against a conserved region of human immunodeficiency virus type 1 gp41 (amino acid residues 731-752) is uniquely directed against a conformational epitope.

Amino acids 731-752 (731PRGPDRPEGIEEEGGERDRDRS752) of the transmembrane glycoprotein gp41 of human immunodeficiency virus type 1 (HIV-1) are conserved in most virus isolates and are controversially reported to be implicated in virus neutralization. The humoral response in infected patients against this region is poor and humans immunized with gp160 show high levels of antibodies against the peptide but poor neutralization titres. Nonetheless, several groups have succeeded in obtaining neutralizing antibodies against this sequence using different antigen-presenting systems.

Neutralization titres of HIV-1-specific monoclonal antibodies vary according to the batch of primary human peripheral blood lymphocytes, but do not vary coordinately.

Human peripheral blood lymphocytes (PBL) were collected from five healthy adults under standard conditions and on a number of different occasions, and used in neutralization assays of human immunodeficiency virus type 1 (HIV-1) strain IIIB with three monoclonal antibodies (mAbs). Variations in neutralization titre were observed with different batches of PBLs with, for example, titres of ICR39.3b ranging from 1/10 to over 1/40000.

A human IgG1 (b12) specific for the CD4 binding site of HIV-1 neutralizes by inhibiting the virus fusion entry process, but b12 Fab neutralizes by inhibiting a postfusion event.

The human b12 IgG1, specific for the CD4 binding site of the gp120 of HIV-1, was prepared by recombinant DNA technology. It had a high neutralization rate constant (-3.5 x 10(5) M(-1) sec(-1)), although this is about 10-fold less than the values for the best poliovirus or influenza A virus MAbs.

A human CD4+ T-cell line expresses functional CD64 (Fc gamma RI), CD32 (Fc gamma RII), and CD16 (Fc gamma RIII) receptors but these do not enhance the infectivity of HIV-1-IgG complexes.

T cells do not generally express Fc receptors (FcRs). However, we report here that C8166 cells, a human CD4+ T lymphoblastoid cell line, widely used in research into the human immunodeficiency virus type 1 (HIV-1), expressed CD64 (Fc gamma RI), CD32 (Fc gamma RII), and CD16 (Fc gamma RIII) on the plasma membrane as shown by immunostaining with specific monoclonal antibody fragments. Another human CD4+ T lymphoblastoid cell line.

Two neutralizing anti-V3 monoclonal antibodies act by affecting different functions of human immunodeficiency virus type 1.

Monoclonal antibody (MAb) ICR41.1i (rat IgG2a) is specific for a conformation-dependent epitope of human immunodeficiency virus type 1 (HIV-1) V3 , and MAb F58 (mouse IgG1) recognizes the peptide IXXGPGR, at the tip of the V3 loop. Both MAbs neutralized HIV-1 strain IIIB in C8166 and HeLa-T4(CD4) cells.

Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus.

A plant virus, cowpea mosaic virus, expressing a 22 amino acid peptide 731-752 of the gp41 glycoprotein of human immunodeficency virus type 1 (HIV-1 IIIB), was shown previously to stimulate HIV-1 cross reactive neutralizing antibodies in adult C57/BL6 mice. Here some parameters concerning the stimulation of HIV-1-specific neutralizing and ELISA antibody have been determined in adult C57/BL6, C3H/He-mg and BALB/c mice. Two injections per mouse of all CPMV-HIV/1 doses tested (100, 10 and 1 microgram chimera which contained, respectively, 1700, 170 and 17 ng HIV peptide per injection) stimulated a strong serum neutralizing antibody response in all mice.

Human immunodeficiency virus type 1-neutralizing antibodies raised to a glycoprotein 41 peptide expressed on the surface of a plant virus.

An oligonucleotide encoding the amino acids 731-752 of the gp41 envelope protein of the human immunodeficiency virus type 1 strain IIIB, which is known to induce cross-reactive neutralizing antibodies in humans, was inserted into a full-length clone of the RNA encoding the coat proteins of cowpea mosaic virus (RNA 2 of CPMV). When transfected together with RNA 1 of CPMV, transcribed RNA 2 was able to replicate in plants and form infectious virions (CPMV-HIV). Purified virions were injected subcutaneously with alum adjuvant into adult C57/BL6 mice to determine their ability to stimulate ELISA and neutralizing antibody specific for HIV-1.

Neutralization escape mutants of type A influenza virus are readily selected by antisera from mice immunized with whole virus: a possible mechanism for antigenic drift.

It is not fully understood how antigenic drift of the haemagglutinin of type A influenza virus in man occurs in the presence of the expected polyclonal antibody response to the five antigenic sites, A to E. Here we show that 12% (11/92) of sera from mice which had mounted a secondary immune response to inactivated influenza virus were able to select escape mutants. No escape mutant was selected with serum from nonimmunized mice (0/65).

Single- and multi-hit kinetics of immunoglobulin G neutralization of human immunodeficiency virus type 1 by monoclonal antibodies.

A quantal assay, based on syncytium formation in the human T cell leukaemia-derived C8166 cell line, was used to determine the kinetics of human immuno-deficiency virus type 1 (HIV-1) strain IIIB neutralization. Three rat monoclonal antibodies (MAbs) were used, under physiological conditions of temperature and antibody concentration. MAb ICR39.

Production of long-lived neutralizing antibodies to HIV-1 IIIB in mice with a vaccinia recombinant virus-infected cell vaccine expressing gp160.

A formaldehyde-fixed cell vaccine in adjuvant (syngeneic cells infected with a vaccinia virus recombinant expressing gp160: vacc-gp160) stimulated only nonneutralizing antibody when used on its own in four strains of mice, but a similar nonfixed cell vaccine stimulated neutralizing antibodies up to a titer of 1/320 in C57BL/6 (H-2b) mice previously infected with live vacc-gp160. Synthesis of ELISA antibodies to rgp120 or rgp160 did not correspond closely to the synthesis of neutralizing antibodies and should not therefore be used to monitor the production of neutralizing antibody. The ELISA antibody response produced by boosting with the cell vaccine made with the vaccinia virus expressing gp160 under the control of a T7 promoter (vacc-gp160-PT7) was as high as that in mice given an approximately 10-fold higher dose of purified rgp160.