Marta Dykhuizen Shore

Bio: Marta Dykhuizen Shore is an academic researcher from University of Minnesota. The author has contributed to research in topics: Simian immunodeficiency virus & Pore water pressure. The author has an hindex of 5, co-authored 7 publications receiving 699 citations.

Propagation and Dissemination of Infection after Vaginal Transmission of Simian Immunodeficiency Virus

Abstract: In the current global AIDS pandemic, more than half of new human immunodeficiency virus type 1 (HIV-1) infections are acquired by women through intravaginal HIV exposure. For this study, we explored pathogenesis issues relevant to the development of effective vaccines to prevent infection by this route, using an animal model in which female rhesus macaques were exposed intravaginally to a high dose of simian immunodeficiency virus (SIV). We examined in detail the events that transpire from hours to a few days after intravaginal SIV exposure through week 4 to provide a framework for understanding the propagation, dissemination, and establishment of infection in lymphatic tissues (LTs) during the acute stage of infection. We show that the mucosal barrier greatly limits the infection of cervicovaginal tissues, and thus the initial founder populations of infected cells are small. While there was evidence of rapid dissemination to distal sites, we also show that continuous seeding from an expanding source of production at the portal of entry is likely critical for the later establishment of a productive infection throughout the systemic LTs. The initially small founder populations and dependence on continuous seeding to establish a productive infection in systemic LTs define a small window of maximum vulnerability for the virus in which there is an opportunity for the host, vaccines, or other interventions to prevent or control infection.

Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection

Abstract: In studies of sexual mucosal transmission and early stages of simian immunodeficiency virus (SIV) and HIV infections, productive infection predominates in CD4+ T cell populations, in both ostensibly resting and activated cells. The surprising ability of SIV and HIV to replicate in resting cells in vivo, in contrast to propagation of infection in vitro, suggested a model in which during the early stages of infection these viruses exploit the greater availability of resting cells to maintain unbroken chains of transmission from an infected resting cell to another resting cell nearby. Because immune activation in response to infection provides more activated CD4+ T cells, these viruses take advantage of the greater efficiency of virus production and spread in activated cells for propagation and dissemination of infection. In this article, we report the results of experimental tests of this model, including visualization at the light microscopic level and direct analysis of virus production by cells in tissues. Analysis of tissues of rhesus macaques inoculated intravaginally or i.v. with SIV supports the proposed roles of target cell availability, susceptibility, and virus production by infected resting and activated CD4+ T cells in mucosal transmission and early infection, and points to a potential role for topical anti-inflammatory agents in moderating the initial propagation of infection.

Communication managers in the dominant coalition : Power attributes and communication practices

Abstract: Purpose – The purpose of this paper is to examine formal and informal types of power, and identify the characteristics of corporate communications managers who are in the dominant coalition.Design/methodology/approach – The paper reports on results of a survey sent to a representative sample of S&P 500 corporate communications managers and CEOs in the USA Data about industry sector, company size, annual revenue and profitability were collected for the responding companies and a random sample of 100 non‐responding companies. The responding companies (n=161) did not significantly differ from the non‐responding companiesFindings – The paper finds that four attributes of informal power differentiate communications managers who are in the dominant coalition from those who are not: reciprocal trust, strategic business decision‐making, social inclusion and communication expertise.Research limitations/implications – Future research should explore whether any of the 37 percent of communications managers in the dom...

The Evolution of Sulfide in Shallow Aquatic Ecosystem Sediments: An Analysis of the Roles of Sulfate, Organic Carbon, and Iron and Feedback Constraints Using Structural Equation Modeling

Abstract: The generation of elevated concentrations of sulfide in sediment pore waters that are toxic to rooted macrophytes is problematic in both marine and freshwaters In marine waters, biogeochemical conditions that lead to toxic levels of sulfide generally relate to factors that affect oxygen dynamics or the sediment iron concentration In freshwaters, increases in surface water sulfate have been implicated in decline of Zizania palustris (wild rice), which is important in wetlands across the Great Lakes region of North America We developed a structural equation (SE) model to elucidate key variables that govern the evolution of sulfide in pore waters in shallow aquatic habitats that are potentially capable of supporting wild rice The conceptual basis for the model is the hypothesis that dissimilatory sulfate reduction is limited by the availability of both sulfate and total organic carbon (TOC) in the sediment The conceptual model also assumes that pore water sulfide concentrations are constrained by the availability of pore water iron and that sediment iron supports the supply of dissolved iron to the pore water A key result from the SE model is that variations in three external variables (sulfate, sediment TOC, and sediment iron) contribute nearly equally to the observed variations in pore water sulfide As a result, management efforts to mitigate against the toxic effects of pore water sulfide on macrophytes such as wild rice should approach defining a protective sulfate threshold as an exercise tailored to the geochemistry of each site that quantitatively considers the effects of ambient concentrations of sediment Fe and TOC

Considering the Role of “Need for Cognition” in Students' Acceptance of Climate Change & Evolution

Abstract: Anthropogenic climate change (ACC) and evolution are examples of issues that are perceived differently by scientists and the general public. Within the scientific community, there are clear consensuses that human activities are increasing global temperatures (ACC) and that evolutionary mechanisms have led to the biodiversity of life on Earth (evolution). However, there is much debate in the public discourse about the scientific evidence supporting these topics. The purpose of our study was to explore the relationship between a student's need for cognition (NFC) — preference to engage in and enjoy thinking — and the student's acceptance of ACC and evolution. The results revealed that students with a higher NFC were more accepting of both ACC and evolution. Future investigations should include evaluating the efficacy of different instructional techniques on NFC and acceptance of polarizing topics such as evolution and ACC.

Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection.

Abstract: It has recently been established that both acute human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are accompanied by a dramatic and selective loss of memory CD4+ T cells predominantly from the mucosal surfaces. The mechanism underlying this depletion of memory CD4+ T cells (that is, T-helper cells specific to previously encountered pathogens) has not been defined. Using highly sensitive, quantitative polymerase chain reaction together with precise sorting of different subsets of CD4+ T cells in various tissues, we show that this loss is explained by a massive infection of memory CD4+ T cells by the virus. Specifically, 30-60% of CD4+ memory T cells throughout the body are infected by SIV at the peak of infection, and most of these infected cells disappear within four days. Furthermore, our data demonstrate that the depletion of memory CD4+ T cells occurs to a similar extent in all tissues. As a consequence, over one-half of all memory CD4+ T cells in SIV-infected macaques are destroyed directly by viral infection during the acute phase-an insult that certainly heralds subsequent immunodeficiency. Our findings point to the importance of reducing the cell-associated viral load during acute infection through therapeutic or vaccination strategies.

Peak SIV replication in resting memory CD4 + T cells depletes gut lamina propria CD4 + T cells

Abstract: In early simian immunodeficiency virus (SIV) and human immunodeficiency virus-1 (HIV-1) infections, gut-associated lymphatic tissue (GALT), the largest component of the lymphoid organ system, is a principal site of both virus production and depletion of primarily lamina propria memory CD4+ T cells; that is, CD4-expressing T cells that previously encountered antigens and microbes and homed to the lamina propria of GALT. Here, we show that peak virus production in gut tissues of SIV-infected rhesus macaques coincides with peak numbers of infected memory CD4+ T cells. Surprisingly, most of the initially infected memory cells were not, as expected, activated but were instead immunophenotypically 'resting' cells that, unlike truly resting cells, but like the first cells mainly infected at other mucosal sites and peripheral lymph nodes, are capable of supporting virus production. In addition to inducing immune activation and thereby providing activated CD4+ T-cell targets to sustain infection, virus production also triggered an immunopathologically limiting Fas-Fas-ligand-mediated apoptotic pathway in lamina propria CD4+ T cells, resulting in their preferential ablation. Thus, SIV exploits a large, resident population of resting memory CD4+ T cells in GALT to produce peak levels of virus that directly (through lytic infection) and indirectly (through apoptosis of infected and uninfected cells) deplete CD4+ T cells in the effector arm of GALT. The scale of this CD4+ T-cell depletion has adverse effects on the immune system of the host, underscoring the importance of developing countermeasures to SIV that are effective before infection of GALT.

The immune response during acute HIV-1 infection: clues for vaccine development.

Abstract: The early immune response to HIV-1 infection is likely to be an important factor in determining the clinical course of disease. Recent data indicate that the HIV-1 quasispecies that arise following a mucosal infection are usually derived from a single transmitted virus. Moreover, the finding that the first effective immune responses drive the selection of virus escape mutations provides insight into the earliest immune responses against the transmitted virus and their contributions to the control of acute viraemia. Strong innate and adaptive immune responses occur subsequently but they are too late to eliminate the infection. In this Review, we discuss recent studies on the kinetics and quality of early immune responses to HIV-1 and their implications for developing a successful preventive HIV-1 vaccine.

Targeting early infection to prevent HIV-1 mucosal transmission

Abstract: Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.

Glycerol monolaurate prevents mucosal SIV transmission

Abstract: Clinical trials of microbicides as a means of preventing the transmission of HIV-1 to women have proved disappointing. Now a study in the simian immunodeficiency virus (SIV)–rhesus macaque vaginal transmission model for HIV infection suggests that a prophylactic approach might yet be worth pursuing. The commonly used antimicrobial compound glycerol monolaurate (GML) was found to suppress SIV infection even after repeated virus exposure. But its mechanism of action was surprising. The host's inflammatory response to the virus, rather than helping, was shown to fuel the infection by recruiting the very CD4+ T cells that the virus targets. GML's prophylactic action appeared to result from its ability to block this host response, rather than from a direct effect on the virus. This points to cell signalling and innate host responses in the mucosal cells as potential targets for drugs and vaccines aimed at preventing infection by HIV — and by other pathogens too if they use similar infection strategies. Glycerol monolaurate in a microbicide is shown to protect monkeys from infection after intra-vaginal exposure to high doses of SIV. The suppressive activity may be due to the inhibition of target cell recruitment due to glycerol-monolaurate-mediated inhibition of epithelial cell signalling and inflammatory cytokine expression. Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection1, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission2,3,4. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)–rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry5,6. Here we show in this SIV–macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α (also known as CCL20), plasmacytoid dendritic cells and CCR5+cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4+ T cells to fuel this obligate expansion. We then show that glycerol monolaurate—a widely used antimicrobial compound7 with inhibitory activity against the production of MIP-3α and other proinflammatory cytokines8—can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission.