Browsing by Type "journal article postprints"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item A Landscape Analysis of HIV Cure-Related Clinical Research in 2019(Elsevier, 2020-09-02) Barr, Liz; Jefferys, RichardObjectives In 2018, we surveyed investigators conducting HIV cure-related clinical research, drawing on information from the online listing established by Treatment Action Group (TAG). The purpose of the survey was to facilitate a landscape analysis of the field. In 2019, we fielded a second survey in order to provide updated information and assess any shifts in the landscape. Methods Trials and observational studies listed as of August 16, 2019 formed the sample set. Survey questions addressed funding, trial development, recruitment, enrollment, participant demographics, antiretroviral therapy status, HIV reservoir assays, invasive procedures, study completion, data sharing and dissemination plans. A survey was sent to the contact(s) for each study. Supplemental information was collected from clinicaltrials.gov and available presentations/publications of study results. Results A total of 97 interventional trials and 36 observational studies were identified, with 30 including analytical treatment interruptions. Total projected enrollment is 13,732 participants, with observational studies contributing the majority (8,325). Most interventional trials are in early phases. The majority of current research is located in the USA, involves predominately male participants and is limited in racial and ethnic diversity. Prespecified demographic enrollment targets are rare. Two thirds of respondents to our previous survey reported that enrollment is progressing more slowly than anticipated. Conclusions A diverse range of interventions are being evaluated in HIV cure research, but participant diversity is far from optimal with a continuing underrepresentation of women. Broadening inclusion and geographic reach will be necessary to achieve the goal of developing widely effective, safe and accessible curative interventions.Item Spermathecal variation in temperate Opiliones(Oxford University Press, 2020-08-17) Zulekha, Karachiwalla; Tagide, deCarvalho; Mercedes, BurnsMost arachnid fertilization occurs internally, allowing for a variety of post-copulatory mechanisms to take place. Females are expected to exert some level of control over sperm fate when 1) the point of gametic fusion is particularly distant from the point of oogenesis, 2) the time of syngamy is significantly later than the time of mating, 3) sperm are non-motile, and/or 4) the morphology of females allows for selective containment of sperm. Many of these conditions are met in Opiliones (a.k.a. “harvesters,” “harvestmen,” or “daddy-longlegs”), where we have evidence of sexual antagonism, multiple mating, and delayed oviposition for a number of species. We used confocal laser scanning microscopy to capture and analyze images of harvester spermathecae, structures within the genitalia of female arthropods that store and maintain sperm after copulation. Spermathecal morphology may have critical function in controlling seminal movement. We anticipated that species with previously identified traits associated with sexual antagonism would also have thicker and/or relatively more complex spermathecae. We examined spermathecal morphology in thirteen species of Leiobunum and one species of Hadrobunus, which were collected from North America and Japan. Our results show that eight species had structures consisting of a single chamber with no or partial invagination, and the remainder had multiple cuticular invaginations producing 2-3 lumina within the spermathecae. Using phylogenetic multivariate comparative methods, we estimated a trend towards cross-correlation between conflict and spermathecal traits. Some, but not all, of the species with thicker, more complex spermathecae had morphological traits associated with sexual conflict (larger body size, thicker genital muscle). In conclusion, we discuss methods to elucidate spermathecal mechanism and sperm precedence in these species. Confocal microscopy allowed us to visualize internal structures difficult to interpret with two-dimensional brightfield microscopy, a technique that could be applied to the characterization of internal reproductive structures in other arthropods.Item Surface Glycoproteins of Exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function(American Chemical Society, 2016-10-20) Chauhan, Sitara; Danielson, Steven; Clements, Virginia; Edwards, Nathan; Ostrand-Rosenberg, Suzanne; Fenselau, CatherineIn this report, we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSCs), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSCs. We report successful modification of a surface chemistry method for use with exosomes and identify 21 surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSCs. These glycoprotein identities and functionalities are compared with 93 N-linked glycoproteins identified on the surface of the parental cells. As with the lysate proteomes examined previously, the exosome surface N-glycoproteins are primarily a subset of the glycoproteins on the surface of the suppressor cells that released them, with related functions and related potential as therapeutic targets. The “don’t eat me” molecule CD47 and its binding partners thrombospondin-1 (TSP1) and signal regulatory protein α (SIRPα) were among the surface N-glycoproteins detected. Functional bioassays using antibodies to these three molecules demonstrated that CD47, TSP1, and to a lesser extent SIRPα facilitate exosome-mediated MDSC chemotaxis and migration.