is an emerging fungal pathogen responsible for health care-associated outbreaks that arise from persistent surface and skin colonization. We characterized the arsenal of adhesins used by
and ...discovered an uncharacterized adhesin, Surface Colonization Factor (Scf1), and a conserved adhesin, Iff4109, that are essential for the colonization of inert surfaces and mammalian hosts.
is apparently specific to
, and its expression mediates adhesion to inert and biological surfaces across isolates from all five clades. Unlike canonical fungal adhesins, which function through hydrophobic interactions, Scf1 relies on exposed cationic residues for surface association.
is required for
biofilm formation, skin colonization, virulence in systemic infection, and colonization of inserted medical devices.
Cigarette smoke contains nicotine and toxic chemicals and may cause significant neurochemical and anatomical brain changes. Voxel-based morphometry studies have examined the effects of smoking on the ...brain by comparing gray matter volume (GMV) in nicotine dependent individuals (NDs) to nonsmoking individuals with inconsistent results. Although sex differences in neural and behavioral features of nicotine dependence are reported, sex differences in regional GMV remain unknown. The current study examined sex differences in GMV in a large sample of 80 NDs (41 males) and 80 healthy controls (41 males) using voxel-based morphometry. Within NDs, we explored whether GMV was correlated with measures of cigarette use and nicotine dependence. High-resolution T1 structural scans were obtained from all participants. Segmentation and registration were performed in SPM8 using the optimized DARTEL approach. Covariates included age and an estimate of total global GMV. Differences were considered significant at p≤0.001, with a whole brain FWE-corrected cluster probability of p<0.025. Among NDs compared to Controls less GMV was observed in the thalamus and bilateral cerebellum and greater GMV was observed in the bilateral putamen and right parahippocampus. Lower thalamic GMV was observed in both female and male NDs compared to Controls. Female NDs also had lower GMV in the left cerebellum and in the ventral medial and orbitofrontal cortices with no areas of greater GMV. Male NDs had lower GMV in bilateral cerebellum and greater GMV in bilateral parahippocampus and left putamen. Within male NDs, GMV in the left putamen was correlated with number of pack years. This study, conducted in a large cohort, contributes to our knowledge of brain morphology in nicotine addiction and provides additional evidence of sex-specific effects on GMV in NDs. Identifying brain vulnerabilities with respect to sex provides a methodological framework for personalized therapies to improve relapse rates for both sexes.
Respiratory syncytial virus (RSV) interaction with epithelial and dendritic cells (DCs) is known to require divalent cations, suggesting involvement of C-type lectins. RSV infection and maturation of ...primary human DCs are reduced in a dose-dependent manner by EDTA. Therefore, we asked whether RSV infection involves DC-SIGN (CD209) or its isoform L-SIGN (CD299) (DC-SIGN/R). Using surface plasmon resonance analysis, we demonstrated that the attachment G glycoprotein of RSV binds both DC- and L-SIGN. However, neutralization of DC- and L-SIGN on primary human DCs did not inhibit RSV infection, demonstrating that interactions between RSV G and DC- or L-SIGN are not required for productive infection. Thus, neither DC- nor L-SIGN represents a functional receptor for RSV. However, inhibition of these interactions increased DC activation, as evidenced by significantly higher levels of alpha interferon (IFN-α), MIP-1α, and MIP-1β in plasmacytoid DCs (pDCs) exposed to RSV after neutralization of DC-and L-SIGN. To understand the molecular interactions involved, intracellular signaling events triggered by purified RSV G glycoprotein were examined in DC- and L-SIGN-transfected 3T3 cells. RSV G interaction with DC- or L-SIGN was shown to stimulate ERK1 and ERK2 phosphorylation, with statistically significant increases relative to mock-infected cells. Neutralization of DC- and L-SIGN reduced ERK1/2 phosphorylation. With increased DC activation following DC- and L-SIGN neutralization and RSV exposure, these data demonstrate that the signaling events mediated by RSV G interactions with DC/L-SIGN are immunomodulatory and diminish DC activation, which may limit induction of RSV-specific immunity.
Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from ...respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.
Respiratory syncytial virus (RSV) causes recurrent infections throughout life. Vaccine development may depend upon understanding the molecular basis for induction of ineffective immunity. Because ...dendritic cells (DCs) are critically involved in early responses to infection, their interaction with RSV may determine the immunological outcome of RSV infection. Therefore, we investigated the ability of RSV to infect and activate primary mDCs and pDCs using recombinant RSV expressing green fluorescent protein (GFP). At a multiplicity of infection of 5, initial studies demonstrated ∼6.8% of mDC1 and ∼0.9% pDCs were infected. We extended these studies to include CD1c(-)CD141(+) mDC2, finding mDC2 infected at similar frequencies as mDC1. Both infected and uninfected cells upregulated phenotypic markers of maturation. Divalent cations were required for infection and maturation, but maturation did not require viral replication. There is evidence that attachment and entry/replication processes exert distinct effects on DC activation. Cell-specific patterns of RSV-induced maturation and cytokine production were detected in mDC1, mDC2, and pDC. We also demonstrate for the first time that RSV induces significant TIMP-2 production in all DC subsets. Defining the influence of RSV on the function of selected DC subsets may improve the likelihood of achieving protective vaccine-induced immunity.
Growing interest in sustainable seafood has led to the proliferation of third-party certifications and eco-labels. This paper examines the ongoing debate that has surrounded a potential ...government-operated certification program for federally managed fisheries in the United States. Drawing on an analysis of transcripts from the Marine Fishery Advisory Committee meetings between 2007 and 2014, the paper considers the ways the proposed program was justified and how the multi-year discussion led to recommendations that encourage the National Marine Fisheries Service to create a framework for a certification program based on the principles defined in the Magnuson-Stevens Fishery Conservation and Management Act. It is through this discussion that it becomes apparent that sustainability claims extend beyond the scientific domain, making them fruitful grounds for understanding the emergence of policy and how power and legitimacy are negotiated and maintained through the process.
•A potential government run sustainable seafood certification program is discussed.•The shift towards a federal certification is only tenuously linked to conservation.•The debate illustrates a broader negotiation of authority between stakeholders.•How sustainability is socially constructed and by whom has implications for policy.
Given the complexity and multiplicity of goals in natural resource governance, it is not surprising that policy debates are often characterized by contention and competition. Yet at times adversaries ...join together to collaborate to find creative solutions not easily achieved in polarizing forums. We employed qualitative interviews and a quantitative network analysis to investigate a collaborative network that formed to develop a resolution to a challenging natural resource management problem, the conservation of vernal pools. We found that power had become distributed among members, trust had formed across core interests, and social learning had resulted in shared understanding and joint solutions. Furthermore, institutions such as who and when new members joined, norms of inclusion and openness, and the use of small working groups helped create the observed patterns of power, trust, and learning.
Seeking sustainability Ovitz, Kimberly L.; Johnson, Teresa R.
International journal of the commons,
01/2019, Volume:
13, Issue:
1
Journal Article
Peer reviewed
Open access
Achieving resource sustainability in complex social-ecological systems requires employing place-based management mechanisms congruent with the underlying temporal, spatial, and functional dynamics of ...the system in question. However, matching management to system dynamics can prove extremely challenging, as has been illustrated in Maine’s sea urchin fishery where fishery managers have struggled to resolve management spatial scale mismatch for over two decades. In Maine, the spatial scale of management far exceeds the relevant spatial dynamics of the urchin resource and leaves fine-scale urchin aggregations in a de facto open access state. These conditions facilitated the serial overharvest of urchin aggregations, which caused overharvested areas to transition to kelp-dominated ecosystem states that inhibit urchin recruitment. Although fishery actors contemplated adopting a number of fine-scale management alternatives to enhance social-ecological fit in the fishery, to date, no such alternatives have been employed. We adopted an ethnographic research approach and conducted semi-structured key informant interviews, document analysis of archived meeting minutes, and participant observation at co-management meetings and restoration events to explore these fishery dynamics. Following data analysis, we employed Ostrom’s social-ecological systems framework as a diagnostic tool to identify the factors that have influenced management spatial fit in the urchin fishery. Research findings suggest that a number of interacting variables, including harvesters’ heterogeneity and conflicting mental models of the SES, low levels of trust and social capital, and changes in the resource system following collapse impeded the degree of collective action necessary to support fine-scale management. However, changing leadership characteristics and increasing horizontal collaboration between harvesters and scientists have positively influenced governance outcomes in recent years. These conditions provide a window of opportunity for the urchin fishery to transition towards a more adaptive and collaborative governance arrangement more conducive to addressing problems of fit in the urchin fishery.
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