Viremic HIV Infected Individuals with High CD4 T Cells and Functional Envelope Proteins Show Anti-gp41 Antibodies with Unique Specificity and Function

BACKGROUND: CD4 T-cell decay is variable among HIV-infected individuals. In exceptional cases, CD4 T-cell counts remain stable despite high plasma viremia. HIV envelope glycoprotein (Env) properties, namely tropism, fusion or the ability to induce the NK ligand NKp44L, or host factors that modulate Env cytopathic mechanisms may be modified in such situation. METHODS: We identified untreated HIV-infected individuals showing non-cytopathic replication (VL>10,000 copies/mL and CD4 T-cell decay<50 cells/µL/year, Viremic Non Progressors, VNP) or rapid progression (CD4 T-cells<350 cells/µL within three years post-infection, RP). We isolated full-length Env clones and analyzed their functions (tropism, fusion activity and capacity to induce NKp44L expression on CD4 cells). Anti-Env humoral responses were also analyzed. RESULTS: Env clones isolated from VNP or RP individuals showed no major phenotypic differences. The percentage of functional clones was similar in both groups. All clones tested were CCR5-tropic and showed comparable expression and fusogenic activity. Moreover, no differences were observed in their capacity to induce NKp44L expression on CD4 T cells from healthy donors through the 3S epitope of gp41. In contrast, anti- Env antibodies showed clear functional differences: plasma from VNPs had significantly higher capacity than RPs to block NKp44L induction by autologous viruses. Consistently, CD4 T-cells isolated from VNPs showed undetectable NKp44L expression and specific antibodies against a variable region flanking the highly conserved 3S epitope were identified in plasma samples from these patients. Conversely, despite continuous antigen stimulation, VNPs were unable to mount a broad neutralizing response against HIV. CONCLUSIONS: Env functions (fusion and induction of NKp44L) were similar in viremic patients with slow or rapid progression to AIDS. However, differences in humoral responses against gp41 epitopes nearby 3S sequence may contribute to the lack of CD4 T cell decay in VNPs by blocking the induction of NKp44L by gp41

What does the structure-function relationship of the HIV-1 Tat protein teach us about developing an AIDS vaccine?

The human immunodeficiency virus type 1 (HIV-1) trans-activator of transcription protein Tat is an important factor in viral pathogenesis. In addition to its function as the key trans-activator of viral transcription, Tat is also secreted by the infected cell and taken up by neighboring cells where it has an effect both on infected and uninfected cells. In this review we will focus on the relationship between the structure of the Tat protein and its function as a secreted factor. To this end we will summarize some of the exogenous functions of Tat that have been implicated in HIV-1 pathogenesis and the impact of structural variations and viral subtype variants of Tat on those functions. Finally, since in some patients the presence of Tat-specific antibodies or CTL frequencies are associated with slow or non-progression to AIDS, we will also discuss the role of Tat as a potential vaccine candidate, the advances made in this field, and the importance of using a Tat protein capable of eliciting a protective or therapeutic immune response to viral challenge

Biological versus chronological ovarian age:implications for assisted reproductive technology

<p>Abstract</p> <p>Background</p> <p>Women have been able to delay childbearing since effective contraception became available in the 1960s. However, fertility decreases with increasing maternal age. A slow but steady decrease in fertility is observed in women aged between 30 and 35 years, which is followed by an accelerated decline among women aged over 35 years. A combination of delayed childbearing and reduced fecundity with increasing age has resulted in an increased number and proportion of women of greater than or equal to 35 years of age seeking assisted reproductive technology (ART) treatment.</p> <p>Methods</p> <p>Literature searches supplemented with the authors' knowledge.</p> <p>Results</p> <p>Despite major advances in medical technology, there is currently no ART treatment strategy that can fully compensate for the natural decline in fertility with increasing female age. Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone, the rate of reproductive ageing and ovarian sensitivity to gonadotrophins varies considerably among individuals. Both environmental and genetic factors contribute to depletion of the ovarian oocyte pool and reduction in oocyte quality. Thus, biological and chronological ovarian age are not always equivalent. Furthermore, biological age is more important than chronological age in predicting the outcome of ART. As older patients present increasingly for ART treatment, it will become more important to critically assess prognosis, counsel appropriately and optimize treatment strategies. Several genetic markers and biomarkers (such as anti-Müllerian hormone and the antral follicle count) are emerging that can identify women with accelerated biological ovarian ageing. Potential strategies for improving ovarian response include the use of luteinizing hormone (LH) and growth hormone (GH). When endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone analogues, LH supplementation may help to optimize treatment outcomes for women with biologically older ovaries. Exogenous GH may improve oocyte development and counteract the age-related decline of oocyte quality. The effects of GH may be mediated by insulin-like growth factor-I, which works synergistically with follicle-stimulating hormone on granulosa and theca cells.</p> <p>Conclusion</p> <p>Patients with biologically older ovaries may benefit from a tailored approach based on individual patient characteristics. Among the most promising adjuvant therapies for improving ART outcomes in women of advanced reproductive age are the administration of exogenous LH or GH.</p

Interpretation of Forest Resources at the Individual Tree Level at Purple Mountain, Nanjing City, China, Using WorldView-2 Imagery by Combining GPS, RS and GIS Technologies

This study attempted to measure forest resources at the individual tree level using high-resolution images by combining GPS, RS, and Geographic Information System (GIS) technologies. The images were acquired by the WorldView-2 satellite with a resolution of 0.5 m in the panchromatic band and 2.0 m in the multispectral bands. Field data of 90 plots were used to verify the interpreted accuracy. The tops of trees in three groups, namely ≥10 cm, ≥15 cm, and ≥20 cm DBH (diameter at breast height), were extracted by the individual tree crown (ITC) approach using filters with moving windows of 3 × 3 pixels, 5 × 5 pixels and 7 × 7 pixels, respectively. In the study area, there were 1,203,970 trees of DBH over 10 cm, and the interpreted accuracy was 73.68 ± 15.14% averaged over the 90 plots. The numbers of the trees that were ≥15 cm and ≥20 cm DBH were 727,887 and 548,919, with an average accuracy of 68.74 ± 17.21% and 71.92 ± 18.03%, respectively. The pixel-based classification showed that the classified accuracies of the 16 classes obtained using the eight multispectral bands were higher than those obtained using only the four standard bands. The increments ranged from 0.1% for the water class to 17.0% for Metasequoia glyptostroboides, with an average value of 4.8% for the 16 classes. In addition, to overcome the “mixed pixels” problem, a crown-based supervised classification, which can improve the classified accuracy of both dominant species and smaller classes, was used for generating a thematic map of tree species. The improvements of the crown- to pixel-based classification ranged from −1.6% for the open forest class to 34.3% for Metasequoia glyptostroboides, with an average value of 20.3% for the 10 classes. All tree tops were then annotated with the species attributes from the map, and a tree count of different species indicated that the forest of Purple Mountain is mainly dominated by Quercus acutissima, Liquidambar formosana and Pinus massoniana. The findings from this study lead to the recommendation of using the crown-based instead of the pixel-based classification approach in classifying mixed forests

A Sexuality and Relationship Training Program for Women with Intellectual Disabilities: A Social Story Approach

A multi-method study design involving three different phases was used to develop four social stories that could be used as part of a sexuality and relationship training program for women with intellectual disabilities. Phase 1 entailed a systematic review of the literature and results indicate that social stories provide a suitable methodology for teaching socially desirable responses related to sexuality and relationships. Phase 2 entailed a focus group with women with intellectual disabilities and results showed that they wanted more information about different types of relationships, including romantic relationships. They also wanted to understand what types of behaviour (e.g. different types of greetings) were appropriate for the different types of relationships. Next, four social stories were written based on the results of these two phases. Finally, these four social stories were implemented in Phase 3 with ten caregivers of women with intellectual disabilities in order to evaluate the appropriateness of the stories. Results showed that three of the four social stories were appropriate, and that one required re-writing as it was not appropriate for the specific context, as women at that facility did not have the opportunity to go on dates. A suggestion was made that the story be re-written to reflect romantic relationships as opposed to dating.http://link.springer.com/journal/111952017-09-30hb2016Centre for Augmentative and Alternative Communication (CAAC