JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Innate Defense against Fungal Pathogens.
Cold Spring Harb Perspect Med
PUBLISHED: 11-12-2014
Show Abstract
Hide Abstract
Human fungal infections have been on the rise in recent years and proved increasingly difficult to treat as a result of the lack of diagnostics, effective antifungal therapies, and vaccines. Most pathogenic fungi do not cause disease unless there is a disturbance in immune homeostasis, which can be caused by modern medical interventions, disease-induced immunosuppression, and naturally occurring human mutations. The innate immune system is well equipped to recognize and destroy pathogenic fungi through specialized cells expressing a broad range of pattern recognition receptors (PRRs). This review will outline the cells and PRRs required for effective antifungal immunity, with a special focus on the major antifungal cytokine IL-17 and recently characterized antifungal inflammasomes.
Related JoVE Video
Femoral head and neck excision in cats: medium- to long-term functional outcome in 18 cats.
J. Feline Med. Surg.
PUBLISHED: 11-08-2014
Show Abstract
Hide Abstract
To assess the medium- to long-term functional outcome of cats after femoral head and neck excision (FHNE) using an owner-completed questionnaire.
Related JoVE Video
Cutting Edge: Failure of Antigen-Specific CD4+ T Cell Recruitment to the Kidney during Systemic Candidiasis.
J. Immunol.
PUBLISHED: 10-24-2014
Show Abstract
Hide Abstract
Candida albicans is the leading cause of systemic candidiasis, a fungal disease associated with high mortality and poor treatment options. The kidney is the target organ during infection and whose control is largely dependent on innate immunity, because lymphocytes appear redundant for protection. In this article, we show that this apparent redundancy stems from a failure of Ag-specific CD4(+) T cells to migrate into infected kidneys. In contrast, Ag-specific CD8(+) T cells are recruited normally. Using Ag-loaded immunoliposomes to artificially reverse this defective migration, we show that recruited Ag-specific CD4(+) T cells polarize toward a Th17 phenotype in the kidney and are protective during fungal infection. Therefore, our data explain the redundancy of CD4(+) T cells for defense against systemic infection with C. albicans and have important implications for our understanding of antifungal immunity and the control of renal infections.
Related JoVE Video
Candida albicans colonization and dissemination from the murine gastrointestinal tract: the influence of morphology and Th17 immunity.
Cell. Microbiol.
PUBLISHED: 10-21-2014
Show Abstract
Hide Abstract
The ability of Candida albicans to cause disease is associated with its capacity to undergo morphological transition between yeast and filamentous forms, but the role of morphology in colonisation and dissemination from the gastrointestinal (GI) tract remains poorly defined. To explore this, we made use of wild type and morphological mutants of C. albicans in an established model of GI tract colonization, induced following antibiotic-treatment of mice. Our data reveal that GI tract colonization favours the yeast form of C.?albicans, that there is constitutive low level systemic dissemination in colonized mice that occurs irrespective of fungal morphology, and that colonization is not controlled by Th17 immunity in otherwise immunocompetent animals. These data provide new insights into the mechanisms of pathogenesis and commensalism of C. albicans, and have implications for our understanding of human disease.
Related JoVE Video
Effects of prestudy and poststudy rest on memory: Support for temporal interference accounts of forgetting.
Psychon Bull Rev
PUBLISHED: 09-27-2014
Show Abstract
Hide Abstract
According to interference-based theories of memory, including temporal-distinctiveness theory, both prestudy and poststudy rest should have beneficial impacts on memory performance. Specifically, higher temporal isolation of a memorandum should reduce proactive and/or retroactive interference, and thus should result in better recall. In the present study, we investigated the effects of prestudy and poststudy rest in a free recall paradigm. Participants studied three lists of words, separated by either a short or a long period of low mental activity (a tone-detection task). Recall targeted the second list; this list was studied in one of four conditions, defined by the fully crossed factors of prestudy and poststudy rest duration. Two experiments revealed a beneficial effect of prestudy rest (and, to a lesser extent, of poststudy rest) on list recall. This result is in line with interference-based theories of memory. By contrast, a beneficial effect of prestudy rest is not predicted by consolidation accounts of memory and forgetting; our results thus require additional assumptions and/or a better specification of the consolidation process and its time course in order to be reconciled with consolidation theory.
Related JoVE Video
Dual doping effects (site blockage and electronic promotion) imposed by adatoms on Pd nanocrystals for catalytic hydrogen production.
Chem. Commun. (Camb.)
PUBLISHED: 09-25-2014
Show Abstract
Hide Abstract
Three distinctive doping effects to modify the electronic and geometric properties of Pd nanocrystals for HCOOH decomposition to H2/CO2 are presented: Bi atoms take preferable residence on higher index sites, which leads to a reduction in HCOOH dehydration; Te atoms dwell favourably on terrace sites, which reduces the rate of dehydrogenation; Ag atoms, without site specificity, induce strong electronic effects to promote the activity on the dwindling number of surface Pd sites at high coverage.
Related JoVE Video
Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens.
Nat. Immunol.
PUBLISHED: 07-01-2014
Show Abstract
Hide Abstract
Neutrophils are critical for antifungal defense, but the mechanisms that clear hyphae and other pathogens that are too large to be phagocytosed remain unknown. We found that neutrophils sensed microbe size and selectively released neutrophil extracellular traps (NETs) in response to large pathogens, such as Candida albicans hyphae and extracellular aggregates of Mycobacterium bovis, but not in response to small yeast or single bacteria. NETs were fundamental in countering large pathogens in vivo. Phagocytosis via dectin-1 acted as a sensor of microbe size and prevented NET release by downregulating the translocation of neutrophil elastase (NE) to the nucleus. Dectin-1 deficiency led to aberrant NET release and NET-mediated tissue damage during infection. Size-tailored neutrophil responses cleared large microbes and minimized pathology when microbes were small enough to be phagocytosed.
Related JoVE Video
Metabolism impacts upon Candida immunogenicity and pathogenicity at multiple levels.
Trends Microbiol.
PUBLISHED: 05-20-2014
Show Abstract
Hide Abstract
Metabolism is integral to the pathogenicity of Candida albicans, a major fungal pathogen of humans. As well as providing the platform for nutrient assimilation and growth in diverse host niches, metabolic adaptation affects the susceptibility of C. albicans to host-imposed stresses and antifungal drugs, the expression of key virulence factors, and fungal vulnerability to innate immune defences. These effects, which are driven by complex regulatory networks linking metabolism, morphogenesis, stress adaptation, and cell wall remodelling, influence commensalism and infection. Therefore, current concepts of Candida-host interactions must be extended to include the impact of metabolic adaptation upon pathogenicity and immunogenicity.
Related JoVE Video
Serotonin and Social Norms: Tryptophan Depletion Impairs Social Comparison and Leads to Resource Depletion in a Multiplayer Harvesting Game.
Psychol Sci
PUBLISHED: 05-08-2014
Show Abstract
Hide Abstract
How do people sustain resources for the benefit of individuals and communities and avoid the tragedy of the commons, in which shared resources become exhausted? In the present study, we examined the role of serotonin activity and social norms in the management of depletable resources. Healthy adults, alongside social partners, completed a multiplayer resource-dilemma game in which they repeatedly harvested from a partially replenishable monetary resource. Dietary tryptophan depletion, leading to reduced serotonin activity, was associated with aggressive harvesting strategies and disrupted use of the social norms given by distributions of other players' harvests. Tryptophan-depleted participants more frequently exhausted the resource completely and also accumulated fewer rewards than participants who were not tryptophan depleted. Our findings show that rank-based social comparisons are crucial to the management of depletable resources, and that serotonin mediates responses to social norms.
Related JoVE Video
Effect of a genomic classifier test on clinical practice decisions for patients with high-risk prostate cancer after surgery.
BJU Int.
PUBLISHED: 05-03-2014
Show Abstract
Hide Abstract
To evaluate the impact of a genomic classifier (GC) test for predicting metastasis risk after radical prostatectomy (RP) on urologists' decision-making about adjuvant treatment of patients with high-risk prostate cancer.
Related JoVE Video
Fungal chitin dampens inflammation through IL-10 induction mediated by NOD2 and TLR9 activation.
PLoS Pathog.
PUBLISHED: 04-01-2014
Show Abstract
Hide Abstract
Chitin is an essential structural polysaccharide of fungal pathogens and parasites, but its role in human immune responses remains largely unknown. It is the second most abundant polysaccharide in nature after cellulose and its derivatives today are widely used for medical and industrial purposes. We analysed the immunological properties of purified chitin particles derived from the opportunistic human fungal pathogen Candida albicans, which led to the selective secretion of the anti-inflammatory cytokine IL-10. We identified NOD2, TLR9 and the mannose receptor as essential fungal chitin-recognition receptors for the induction of this response. Chitin reduced LPS-induced inflammation in vivo and may therefore contribute to the resolution of the immune response once the pathogen has been defeated. Fungal chitin also induced eosinophilia in vivo, underpinning its ability to induce asthma. Polymorphisms in the identified chitin receptors, NOD2 and TLR9, predispose individuals to inflammatory conditions and dysregulated expression of chitinases and chitinase-like binding proteins, whose activity is essential to generate IL-10-inducing fungal chitin particles in vitro, have also been linked to inflammatory conditions and asthma. Chitin recognition is therefore critical for immune homeostasis and is likely to have a significant role in infectious and allergic disease.
Related JoVE Video
Topical application of imiquimod as a treatment for chromoblastomycosis.
Clin. Infect. Dis.
PUBLISHED: 03-14-2014
Show Abstract
Hide Abstract
Chromoblastomycosis is a subcutaneous mycosis that remains a therapeutic challenge, with no standard treatment and high rates of relapse. On the basis of our recent discoveries in mouse models, we tested the efficacy of topical applications of imiquimod to treat patients afflicted with this chronic fungal infection. We report results of treatment for the first 4 recipients of topical imiquimod, all of whom displayed a marked improvement of their lesions, both with and without concurrent oral antifungal therapy.
Related JoVE Video
Dectin-1 induces M1 macrophages and prominent expansion of CD8+IL-17+ cells in pulmonary Paracoccidioidomycosis.
J. Infect. Dis.
PUBLISHED: 03-05-2014
Show Abstract
Hide Abstract
Dectin-1, the innate immune receptor that recognizes ?-glucan, plays an important role in immunity against fungal pathogens. Paracoccidioides brasiliensis, the etiological agent of paracoccidioidomycosis, has a sugar-rich cell wall mainly composed of mannans and glucans. This fact motivated us to use dectin-1-sufficient and -deficient mice to investigate the role of ?-glucan recognition in the immunity against pulmonary paracoccidioidomycosis. Initially, we verified that P. brasiliensis infection reinforced the tendency of dectin-1-deficient macrophages to express an M2 phenotype. This prevalent antiinflammatory activity of dectin-1(-/-) macrophages resulted in impaired fungicidal ability, low nitric oxide production, and elevated synthesis of interleukin 10 (IL-10). Compared with dectin-1-sufficient mice, the fungal infection of dectin-1(-/-) mice was more severe and resulted in enhanced tissue pathology and mortality rates. The absence of dectin-1 has also impaired the production of T-helper type 1 (Th1), Th2, and Th17 cytokines and the activation and migration of T cells to the site of infection. Remarkably, dectin-1 deficiency increased the expansion of regulatory T cells and reduced the differentiation of T cells to the IL-17(+) phenotype, impairing the migration of IL-17(+)CD8(+) T cells and polymorphonuclear cells to infected tissues. In conclusion, dectin-1 exerts an important protective role in pulmonary paracoccidioidomycosis by controlling the innate and adaptive phases of antifungal immunity.
Related JoVE Video
AIDS-related mycoses: the way forward.
Trends Microbiol.
PUBLISHED: 03-04-2014
Show Abstract
Hide Abstract
The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.
Related JoVE Video
A neglected epidemic: fungal infections in HIV/AIDS.
Trends Microbiol.
PUBLISHED: 01-02-2014
Show Abstract
Hide Abstract
Invasive fungal infections (IFIs) are a major cause of HIV-related mortality globally. Despite widespread rollout of combined antiretroviral therapy, there are still up to 1 million deaths annually from IFIs, accounting for 50% of all AIDS-related death. A historic failure to focus efforts on the IFIs that kill so many HIV patients has led to fundamental flaws in the management of advanced HIV infection. This review, based on the EMBO AIDS-Related Mycoses Workshop in Cape Town in July 2013, summarizes the current state of the-art in AIDS-related mycoses, and the key action points required to improve outcomes from these devastating infections.
Related JoVE Video
The expression and prognostic significance of retinoic acid metabolising enzymes in colorectal cancer.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Colorectal cancer is one of the most common types of cancer with over fifty percent of patients presenting at an advanced stage. Retinoic acid is a metabolite of vitamin A and is essential for normal cell growth and aberrant retinoic acid metabolism is implicated in tumourigenesis. This study has profiled the expression of retinoic acid metabolising enzymes using a well characterised colorectal cancer tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosal samples. Immunohistochemistry was performed on the tissue microarray using monoclonal antibodies which we have developed to the retinoic acid metabolising enzymes CYP26A1, CYP26B1, CYP26C1 and lecithin retinol acyl transferase (LRAT) using a semi-quantitative scoring scheme to assess expression. Moderate or strong expression of CYP26A1was observed in 32.5% of cancers compared to 10% of normal colonic epithelium samples (p<0.001). CYP26B1 was moderately or strongly expressed in 25.2% of tumours and was significantly less expressed in normal colonic epithelium (p<0.001). CYP26C1 was not expressed in any sample. LRAT also showed significantly increased expression in primary colorectal cancers compared with normal colonic epithelium (p<0.001). Strong CYP26B1 expression was significantly associated with poor prognosis (HR = 1.239, 95%CI = 1.104-1.390, ?(2) = 15.063, p = 0.002). Strong LRAT was also associated with poorer outcome (HR = 1.321, 95%CI = 1.034-1.688, ?(2) = 5.039, p = 0.025). In mismatch repair proficient tumours strong CYP26B1 (HR = 1.330, 95%CI = 1.173-1.509, ?(2)= 21.493, p<0.001) and strong LRAT (HR = 1.464, 95%CI = 1.110-1.930, ?(2)?= 7.425, p = 0.006) were also associated with poorer prognosis. This study has shown that the retinoic acid metabolising enzymes CYP26A1, CYP26B1 and LRAT are significantly overexpressed in colorectal cancer and that CYP26B1 and LRAT are significantly associated with prognosis both in the total cohort and in those tumours which are mismatch repair proficient. CYP26B1 was independently prognostic in a multivariate model both in the whole patient cohort (HR = 1.177, 95%CI = 1.020-1.216, p = 0.026) and in mismatch repair proficient tumours (HR = 1.255, 95%CI = 1.073-1.467, p = 0.004).
Related JoVE Video
The role of Dectin-2 for host defense against systemic infection with Candida glabrata.
Infect. Immun.
PUBLISHED: 12-16-2013
Show Abstract
Hide Abstract
Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2(-/-)) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance in kidneys, but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2(-/-) mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate, yet significant, decreased phagocytosis of the fungus by the Dectin-2(-/-) macrophages and neutrophils. Neutrophils of Dectin-2(-/-) mice also displayed a lower production of reactive oxygen species (ROS) upon challenge with opsonized C. glabrata or C. albicans. This study suggests that Dectin-2 is important in host defense against C. glabrata and provides new insights in the host defense mechanisms against this important fungal pathogen.
Related JoVE Video
Sulfidation of silver nanoparticles: natural antidote to their toxicity.
Environ. Sci. Technol.
PUBLISHED: 11-15-2013
Show Abstract
Hide Abstract
Nanomaterials are highly dynamic in biological and environmental media. A critical need for advancing environmental health and safety research for nanomaterials is to identify physical and chemical transformations that affect the nanomaterial properties and their toxicity. Silver nanoparticles, one of the most toxic and well-studied nanomaterials, readily react with sulfide to form Ag(0)/Ag2S core-shell particles. Here, we show that sulfidation decreased silver nanoparticle toxicity to four diverse types of aquatic and terrestrial eukaryotic organisms (Danio rerio (zebrafish), Fundulus heteroclitus (killifish), Caenorhabditis elegans (nematode worm), and the aquatic plant Lemna minuta (least duckweed)). Toxicity reduction, which was dramatic in killifish and duckweed even for low extents of sulfidation (about 2 mol % S), is primarily associated with a decrease in Ag(+) concentration after sulfidation due to the lower solubility of Ag2S relative to elemental Ag (Ag(0)). These results suggest that even partial sulfidation of AgNP will decrease the toxicity of AgNPs relative to their pristine counterparts. We also show that, for a given organism, the presence of chloride in the exposure media strongly affects the toxicity results by affecting Ag speciation. These results highlight the need to consider environmental transformations of NPs in assessing their toxicity to accurately portray their potential environmental risks.
Related JoVE Video
Money, well-being, and loss aversion: does an income loss have a greater effect on well-being than an equivalent income gain?
Psychol Sci
PUBLISHED: 10-14-2013
Show Abstract
Hide Abstract
Higher income is associated with greater well-being, but do income gains and losses affect well-being differently? Loss aversion, whereby losses loom larger than gains, is typically examined in relation to decisions about anticipated outcomes. Here, using subjective-well-being data from Germany (N = 28,723) and the United Kingdom (N = 20,570), we found that losses in income have a larger effect on well-being than equivalent income gains and that this effect is not explained by diminishing marginal benefits of income to well-being. Our findings show that loss aversion applies to experienced losses, challenging suggestions that loss aversion is only an affective-forecasting error. By failing to account for loss aversion, longitudinal studies of the relationship between income and well-being may have overestimated the positive effect of income on well-being. Moreover, societal well-being might best be served by small and stable income increases, even if such stability impairs long-term income growth.
Related JoVE Video
Competitive Sorption of Pb(II) and Zn(II) on Polyacrylic Acid-Coated Hydrated Aluminum-Oxide Surfaces.
Environ. Sci. Technol.
PUBLISHED: 10-11-2013
Show Abstract
Hide Abstract
Natural organic matter (NOM) often forms coatings on minerals. Such coatings are expected to affect metal-ion sorption due to abundant sorption sites in NOM and potential modifications to mineral surfaces, but such effects are poorly understood in complex multicomponent systems. Using poly(acrylic acid) (PAA), a simplified analog of NOM containing only carboxylic groups, Pb(II) and Zn(II) partitioning between PAA coatings and ?-Al2O3 (1-102) and (0001) surfaces was investigated using long-period X-ray standing wave-florescence yield spectroscopy. In the single-metal-ion systems, PAA was the dominant sink for Pb(II) and Zn(II) for ?-Al2O3(1-102) (63% and 69%, respectively, at 0.5 ?M metal ions and pH 6.0). In equi-molar mixed-Pb(II)-Zn(II) systems, partitioning of both ions onto ?-Al2O3(1-102) decreased compared with the single-metal-ion systems; however, Zn(II) decreased Pb(II) sorption to a greater extent than vice versa, suggesting that Zn(II) outcompeted Pb(II) for ?-Al2O3(1-102) sorption sites. In contrast, >99% of both metal ions sorbed to PAA when equi-molar Pb(II) and Zn(II) were added simultaneously to PAA/?-Al2O3(0001). PAA outcompeted both ?-Al2O3 surfaces for metal sorption but did not alter their intrinsic order of reactivity. This study suggests that single-metal-ion sorption results cannot be used to predict multimetal-ion sorption at NOM/metal-oxide interfaces when NOM is dominated by carboxylic groups.
Related JoVE Video
Dectin-1 is essential for reverse transcytosis of glycosylated SIgA-antigen complexes by intestinal M cells.
PLoS Biol.
PUBLISHED: 09-01-2013
Show Abstract
Hide Abstract
Intestinal microfold (M) cells possess a high transcytosis capacity and are able to transport a broad range of materials including particulate antigens, soluble macromolecules, and pathogens from the intestinal lumen to inductive sites of the mucosal immune system. M cells are also the primary pathway for delivery of secretory IgA (SIgA) to the gut-associated lymphoid tissue. However, although the consequences of SIgA uptake by M cells are now well known and described, the mechanisms whereby SIgA is selectively bound and taken up remain poorly understood. Here we first demonstrate that both the C?1 region and glycosylation, more particularly sialic acid residues, are involved in M cell-mediated reverse transcytosis. Second, we found that SIgA is taken up by M cells via the Dectin-1 receptor, with the possible involvement of Siglec-5 acting as a co-receptor. Third, we establish that transcytosed SIgA is taken up by mucosal CX3CR1? dendritic cells (DCs) via the DC-SIGN receptor. Fourth, we show that mucosal and systemic antibody responses against the HIV p24-SIgA complexes administered orally is strictly dependent on the expression of Dectin-1. Having deciphered the mechanisms leading to specific targeting of SIgA-based Ag complexes paves the way to the use of such a vehicle for mucosal vaccination against various infectious diseases.
Related JoVE Video
Rural Embedded Assistants for Community Health (REACH) network: first-person accounts in a community-university partnership.
Am J Community Psychol
PUBLISHED: 08-24-2013
Show Abstract
Hide Abstract
Community research and action projects undertaken by community-university partnerships can lead to contextually appropriate and sustainable community improvements in rural and urban localities. However, effective implementation is challenging and prone to failure when poorly executed. The current paper seeks to inform rural community-university partnership practice through consideration of first-person accounts from five stakeholders in the Rural Embedded Assistants for Community Health (REACH) Network. The REACH Network is a unique community-university partnership aimed at improving rural health services by identifying, implementing, and evaluating innovative health interventions delivered by local caregivers. The first-person accounts provide an insiders perspective on the nature of collaboration. The unique perspectives identify three critical challenges facing the REACH Network: trust, coordination, and sustainability. Through consideration of the challenges, we identified several strategies for success. We hope readers can learn their own lessons when considering the details of our partnerships efforts to improve the delivery infrastructure for rural healthcare.
Related JoVE Video
Development of an Illumina-based ChIP-exonuclease method provides insight into FoxA1-DNA binding properties.
Genome Biol.
PUBLISHED: 08-23-2013
Show Abstract
Hide Abstract
ChIP-exonuclease (ChIP-exo) is a modified ChIP-seq approach for high resolution mapping of transcription factor DNA sites. We describe an Illumina-based ChIP-exo method which provides a global improvement of the data quality of estrogen receptor (ER) ChIP and insights into the motif structure for key ER-associated factors. ChIP-exo of the ER pioneer factor FoxA1 identifies protected DNA with a predictable 8 base pair overhang from the Forkhead motif, which we term mesas. We show that mesas occur in multiple cellular contexts and exist as single or overlapping motifs. Our Illumina based ChIP-exo provides high resolution mapping of transcription factor binding sites.
Related JoVE Video
Dietary intakes of pesticides based on community duplicate diet samples.
Sci. Total Environ.
PUBLISHED: 07-12-2013
Show Abstract
Hide Abstract
The calculation of dietary intake of selected pesticides was accomplished using food samples collected from individual representatives of a defined demographic community using a community duplicate diet approach. A community of nine participants was identified in Apopka, FL from which intake assessments of organophosphate (OP) and pyrethroid pesticides were made. From these nine participants, sixty-seven individual samples were collected and subsequently analyzed by gas chromatography/mass spectrometry. Measured concentrations were used to estimate dietary intakes for individuals and for the community. Individual intakes of total OP and pyrethroid pesticides ranged from 6.7 to 996ng and 1.2 to 16,000ng, respectively. The community intake was 256ng for OPs and 3430ng for pyrethroid pesticides. The most commonly detected pesticide was permethrin, but the highest overall intake was of bifenthrin followed by esfenvalerate. These data indicate that the community in Apopka, FL, as represented by the nine individuals, was potentially exposed to both OP and pyrethroid pesticides at levels consistent with a dietary model and other field studies in which standard duplicate diet samples were collected. Higher levels of pyrethroid pesticides were measured than OPs, which is consistent with decreased usage of OPs. The diversity of pyrethroid pesticides detected in food samples was greater than expected. Continually changing pesticide usage patterns need to be considered when determining analytes of interest for large scale epidemiology studies. The Community Duplicate Diet Methodology is a tool for researchers to meet emerging exposure measurement needs that will lead to more accurate assessments of intake which may enhance decisions for chemical regulation. Successfully determining the intake of pesticides through the dietary route will allow for accurate assessments of pesticide exposures to a community of individuals, thereby significantly enhancing the research benefit realized from epidemiological exposure studies.
Related JoVE Video
hMICL and CD123 in combination with a CD45/CD34/CD117 backbone - a universal marker combination for the detection of minimal residual disease in acute myeloid leukaemia.
Br. J. Haematol.
PUBLISHED: 06-20-2013
Show Abstract
Hide Abstract
Real-time quantitative polymerase chain reaction (qPCR) has been extensively validated for the detection of minimal residual disease (MRD) in acute myeloid leukaemia (AML). Meanwhile, multicolour flow cytometry (MFC) has received less attention because the so-called leukaemia-associated immunophenotypes (LAIPs) are generally of lower sensitivity and specificity, and prone to change during therapy. To improve MRD assessment by MFC, we here evaluate the combination of human Myeloid Inhibitory C-type Lectin (hMICL, also termed C-type lectin domain family 12, member A, CLEC12A) and CD 123 (also termed interleukin-3 receptor alpha, IL3RA) in combination with CD34 and CD117 (KIT), as an MRD assay in pre-clinical and clinical testing in 69 AML patients. Spiking experiments revealed that the assay could detect MRD down to 10(-4) in normal bone marrow with sensitivities equalling those of validated qPCR assays. Moreover, it provided at least one MFC MRD marker in 62/69 patients (90%). High levels of hMICL/CD123 LAIPs at the post-induction time-point were a strong prognostic marker for relapse in patients in haematological complete remission (P < 0·001). Finally, in post induction samples, hMICL/CD123 LAIPs were strongly correlated (r = 0·676, P = 0·0008) to applied qPCR targets. We conclude the hMICL/CD123-based MFC assay is a promising MRD tool in AML.
Related JoVE Video
Regiospecific methylation of a dietary flavonoid scaffold selectively enhances IL-1? production following Toll-like receptor 2 stimulation in THP-1 monocytes.
J. Biol. Chem.
PUBLISHED: 06-11-2013
Show Abstract
Hide Abstract
It is now recognized that innate immunity to intestinal microflora plays a significant role in mediating immune health, and modulation of microbial sensing may underpin the impact of plant natural products in the diet or when used as nutraceuticals. In this context, we have examined five classes of plant-derived flavonoids (flavonols, flavones, flavanones, catechins, and cyanidin) for their ability to regulate cytokine release induced by the Toll-like receptor 2 (TLR2) agonist Pam3CSK4. We found that the flavonols selectively co-stimulated IL-1? secretion but had no impact on the secretion of IL-6. Importantly, this costimulation of TLR2-induced cytokine secretion was dependent on regiospecific methylation of the flavonol scaffold with a rank order of quercetin-3,4-dimethylether > quercetin-3-methylether > casticin. The mechanism underpinning this costimulation did not involve enhanced inflammasome activation. In contrast, the methylated flavonols enhanced IL-1? gene expression through transcriptional regulation, involving mechanisms that operate downstream of the initial NF-?B and STAT1 activation events. These studies demonstrate an exquisite level of control of scaffold bioactivity by regiospecific methylation, with important implications for understanding how natural products affect innate immunity and for their development as novel immunomodulators for clinical use.
Related JoVE Video
Mercury isotope signatures as tracers for Hg cycling at the New Idria Hg mine.
Environ. Sci. Technol.
PUBLISHED: 05-28-2013
Show Abstract
Hide Abstract
Mass-dependent fractionation (MDF) and mass-independent fractionation (MIF) of Hg isotopes provides a new tool for tracing Hg in contaminated environments such as mining sites, which represent major point sources of Hg pollution into surrounding ecosystems. Here, we present Hg isotope ratios of unroasted ore waste, calcine (roasted ore), and poplar leaves collected at a closed Hg mine (New Idria, CA, U.S.A.). Unroasted ore waste was isotopically uniform with ?(202)Hg values from -0.09 to 0.16‰ (± 0.10‰, 2 SD), close to the estimated initial composition of the HgS ore (-0.26‰). In contrast, calcine samples exhibited variable ?(202)Hg values ranging from -1.91‰ to +2.10‰. Small MIF signatures in the calcine were consistent with nuclear volume fractionation of Hg isotopes during or after the roasting process. The poplar leaves exhibited negative MDF (-3.18 to -1.22‰) and small positive MIF values (?(199)Hg of 0.02 to 0.21‰). Sequential extractions combined with Hg isotope analysis revealed higher ?(202)Hg values for the more soluble Hg pools in calcines compared with residual HgS phases. Our data provide novel insights into possible in situ transformations of Hg phases and suggest that isotopically heavy secondary Hg phases were formed in the calcine, which will influence the isotope composition of Hg leached from the site.
Related JoVE Video
Effect of chloride on the dissolution rate of silver nanoparticles and toxicity to E. coli.
Environ. Sci. Technol.
PUBLISHED: 05-17-2013
Show Abstract
Hide Abstract
Pristine silver nanoparticles (AgNPs) are not chemically stable in the environment and react strongly with inorganic ligands such as sulfide and chloride once the silver is oxidized. Understanding the environmental transformations of AgNPs in the presence of specific inorganic ligands is crucial to determining their fate and toxicity in the environment. Chloride (Cl(-)) is a ubiquitous ligand with a strong affinity for oxidized silver and is often present in natural waters and in bacterial growth media. Though chloride can strongly affect toxicity results for AgNPs, their interaction is rarely considered and is challenging to study because of the numerous soluble and solid Ag-Cl species that can form depending on the Cl/Ag ratio. Consequently, little is known about the stability and dissolution kinetics of AgNPs in the presence of chloride ions. Our study focuses on the dissolution behavior of AgNPs in chloride-containing systems and also investigates the effect of chloride on the growth inhibition of E.coli (ATCC strain 33876) caused by Ag toxicity. Our results suggest that the kinetics of dissolution are strongly dependent on the Cl/Ag ratio and can be interpreted using the thermodynamically expected speciation of Ag in the presence of chloride. We also show that the toxicity of AgNPs to E.coli at various Cl(-) concentrations is governed by the amount of dissolved AgCl(x)((x-1)-) species suggesting an ion effect rather than a nanoparticle effect.
Related JoVE Video
Sentencing, severity, and social norms: a rank-based model of contextual influence on judgments of crimes and punishments.
Acta Psychol (Amst)
PUBLISHED: 05-11-2013
Show Abstract
Hide Abstract
Context effects have been shown to bias lay peoples evaluations of the severity of crimes and punishments. To investigate the cognitive mechanisms behind these effects, we develop and apply a rank-based social norms approach to judgments of perceived crime seriousness and sentence appropriateness. In Study 1, we find that (a) people believe on average that 84% of people illegally download software more than they do themselves and (b) their judged severity of, and concern about, their own illegal software downloading is predicted not by its amount but by how this amount is believed (typically inaccurately) to rank within a social comparison distribution. Studies 2 and 3 find that the judged appropriateness of a given sentence length is highly dependent on the length of other sentences available in the decision-making context: The same objective sentence was judged as approximately four times stricter when it was the second longest sentence being considered than when it was the fifth longest. It is concluded that the same mechanisms that are used to judge the magnitude of psychophysical stimuli bias judgments about legal matters.
Related JoVE Video
The Dectin-2 family of C-type lectin-like receptors: an update.
Int. Immunol.
PUBLISHED: 04-23-2013
Show Abstract
Hide Abstract
Myeloid and non-myeloid cells express members of the C-type lectin-like receptor (CTLR) family, which mediate crucial cellular functions during immunity and homeostasis. Of relevance here is the dendritic cell-associated C-type lectin-2 (Dectin-2) family of CTLRs, which includes blood dendritic cell antigen 2 (BDCA-2), dendritic cell immunoactivating receptor (DCAR), dendritic cell immunoreceptor (DCIR), Dectin-2, C-type lectin superfamily 8 (CLECSF8) and macrophage-inducible C-type lectin (Mincle). These CTLRs possess a single extracellular conserved C-type lectin-like domain and are capable of mediating intracellular signalling either directly, through integral signalling domains, or indirectly, by associating with signalling adaptor molecules. These receptors recognize a diverse range of endogenous and exogenous ligands, and can function as pattern recognition receptors for several classes of pathogens including fungi, bacteria and parasites, driving both innate and adaptive immunity. In this review, we summarize our knowledge of each of these receptors, highlighting the exciting discoveries that have been made in recent years.
Related JoVE Video
High genetic diversity is not essential for successful introduction.
Ecol Evol
PUBLISHED: 04-13-2013
Show Abstract
Hide Abstract
Some introduced populations thrive and evolve despite the presumed loss of diversity at introduction. We aimed to quantify the amount of genetic diversity retained at introduction in species that have shown evidence of adaptation to their introduced environments. Samples were taken from native and introduced ranges of Arctotheca populifolia and Petrorhagia nanteuilii. Using microsatellite data, we identified the source for each introduction, estimated genetic diversity in native and introduced populations, and calculated the amount of diversity retained in introduced populations. These values were compared to those from a literature review of diversity in native, confamilial populations and to estimates of genetic diversity retained at introduction. Gene diversity in the native range of both species was significantly lower than for confamilials. We found that, on average, introduced populations showing evidence of adaptation to their new environments retained 81% of the genetic diversity from the native range. Introduced populations of P. nanteuilii had higher genetic diversity than found in the native source populations, whereas introduced populations of A. populifolia retained only 14% of its native diversity in one introduction and 1% in another. Our literature review has shown that most introductions demonstrating adaptive ability have lost diversity upon introduction. The two species studied here had exceptionally low native range genetic diversity. Further, the two introductions of A. populifolia represent the largest percentage loss of genetic diversity in a species showing evidence of substantial morphological change in the introduced range. While high genetic diversity may increase the likelihood of invasion success, the species examined here adapted to their new environments with very little neutral genetic diversity. This finding suggests that even introductions founded by small numbers of individuals have the potential to become invasive.
Related JoVE Video
C-type lectin-like receptors of the dectin-1 cluster: ligands and signaling pathways.
Int. Rev. Immunol.
PUBLISHED: 04-11-2013
Show Abstract
Hide Abstract
Innate immunity is constructed around genetically encoded receptors that survey the intracellular and extracellular environments for signs of invading microorganisms. These receptors recognise the invader and through complex intracellular networks of molecular signaling, they destroy the threat whilst instructing effective adaptive immune responses. Many of these receptors, like the Toll-like receptors in particular, are well-known for their ability to mediate downstream responses upon recognition of exogenous or endogenous ligands; however, the emerging family known as the C-type lectin-like receptors contains many members that have a huge impact on immune and homeostatic regulation. Of particular interest here are the C-type lectin-like receptors that make up the Dectin-1 cluster and their intracellular signaling motifs that mediate their functions. In this review, we aim to draw together current knowledge of ligands, motifs and signaling pathways, present downstream of Dectin-1 cluster receptors, and discuss how these dictate their role within biological systems.
Related JoVE Video
Differential adaptation of Candida albicans in vivo modulates immune recognition by dectin-1.
PLoS Pathog.
PUBLISHED: 04-01-2013
Show Abstract
Hide Abstract
The ?-glucan receptor Dectin-1 is a member of the C-type lectin family and functions as an innate pattern recognition receptor in antifungal immunity. In both mouse and man, Dectin-1 has been found to play an essential role in controlling infections with Candida albicans, a normally commensal fungus in man which can cause superficial mucocutaneous infections as well as life-threatening invasive diseases. Here, using in vivo models of infection, we show that the requirement for Dectin-1 in the control of systemic Candida albicans infections is fungal strain-specific; a phenotype that only becomes apparent during infection and cannot be recapitulated in vitro. Transcript analysis revealed that this differential requirement for Dectin-1 is due to variable adaptation of C. albicans strains in vivo, and that this results in substantial differences in the composition and nature of their cell walls. In particular, we established that differences in the levels of cell-wall chitin influence the role of Dectin-1, and that these effects can be modulated by antifungal drug treatment. Our results therefore provide substantial new insights into the interaction between C. albicans and the immune system and have significant implications for our understanding of susceptibility and treatment of human infections with this pathogen.
Related JoVE Video
Sulfidation mechanism for zinc oxide nanoparticles and the effect of sulfidation on their solubility.
Environ. Sci. Technol.
PUBLISHED: 03-07-2013
Show Abstract
Hide Abstract
Environmental transformations of nanoparticles (NPs) affect their properties and toxicity potential. Sulfidation is an important transformation process affecting the fate of NPs containing metal cations with an affinity for sulfide. Here, the extent and mechanism of sulfidation of ZnO NPs were investigated, and the properties of resulting products were carefully characterized. Synchrotron X-ray absorption spectroscopy and X-ray diffraction analysis reveal that transformation of ZnO to ZnS occurs readily at ambient temperature in the presence of inorganic sulfide. The extent of sulfidation depends on sulfide concentration, and close to 100% conversion can be obtained in 5 days given sufficient addition of sulfide. X-ray diffraction and transmission electron microscopy showed formation of primarily ZnS NPs smaller than 5 nm, indicating that sulfidation of ZnO NPs occurs by a dissolution and reprecipitation mechanism. The solubility of partially sulfidized ZnO NPs is controlled by the remaining ZnO core and not quenched by a ZnS shell formed as was observed for partially sulfidized Ag NPs. Sulfidation also led to NP aggregation and a decrease of surface charge. These changes suggest that sulfidation of ZnO NPs alters the behavior, fate, and toxicity of ZnO NPs in the environment. The reactivity and fate of the resulting <5 nm ZnS particles remains to be determined.
Related JoVE Video
Dectin-1 regulates IL-10 production via a MSK1/2 and CREB dependent pathway and promotes the induction of regulatory macrophage markers.
PLoS ONE
PUBLISHED: 02-25-2013
Show Abstract
Hide Abstract
In response to infection by fungal pathogens, the innate immune system recognises specific fungal pathogen associated molecular patterns (PAMPs) via pattern recognition receptors including the C-type lectin dectin-1 and members of the Toll Like Receptor (TLR) family. Stimulation of these receptors leads to the induction of both pro- and anti-inflammatory cytokines. The protein kinases MSK1 and 2 are known to be important in limiting inflammatory cytokine production by macrophages in response to the TLR4 agonist LPS. In this study we show that MSKs are also activated in macrophages by the fungal derived ligand zymosan, as well as the dectin-1 specific agonists curdlan and depleted zymosan, via the ERK1/2 and p38? MAPK pathways. Furthermore, we show that MSKs regulate dectin-1 induced IL-10 production, and that this regulation is dependent on the ability of MSKs to phosphorylate the transcription factor CREB. IL-10 secreted in response to zymosan was able to promote STAT3 phosphorylation via an autocrine feedback loop. Consistent with the decreased IL-10 secretion in MSK1/2 knockout macrophages, these cells also had decreased STAT3 tyrosine phosphorylation relative to wild type controls after stimulation with zymosan. We further show that the reduction in IL-10 production in the MSK1/2 macrophages results in increased secretion of IL-12p40 in response to zymosan relative to wild type controls. The production of high levels of IL-10 but low levels of IL-12 has previously been associated with an M2b or regulatory macrophage phenotype, which was initially described in macrophages stimulated with a combination of immune complexes and LPS. We found that zymosan, via dectin-1 activation, also leads to the expression of SphK1 and LIGHT, markers of a regulatory like phenotype in mouse macrophages. The expression of these makers was further reinforced by the high level of IL-10 secreted in response to zymosan stimulation.
Related JoVE Video
Dectin-1 plays a redundant role in the immunomodulatory activities of ?-glucan-rich ligands in vivo.
Microbes Infect.
PUBLISHED: 02-11-2013
Show Abstract
Hide Abstract
?-Glucans are known for their ability to trigger both protective and damaging immune responses. Here we have explored the role of the beta-glucan receptor Dectin-1 in archetypical models of protective and non-protective immunomodulation induced by beta-glucan rich ligands. In the first model, we explored the role of Dectin-1 in the ability of soluble purified ?-glucans to mediate protection against systemic Staphylococcus aureus infection in mice. In the second model, we explored the role of Dectin-1 in zymosan induced multiple organ dysfunction syndrome. In both cases, these ?-glucan rich compounds had marked effects in vivo which were unaltered by Dectin-1 deficiency, suggesting that this receptor has a redundant role in these murine models.
Related JoVE Video
Pain ratings reflect cognitive context: a range frequency model of pain perception.
Pain
PUBLISHED: 01-30-2013
Show Abstract
Hide Abstract
When painful stimuli are evaluated at the time they are experienced, judgments are made not in isolation but with reference to other experienced stimuli. We tested a specific quantitative model of how such context effects occur. Participants experienced 3 blocks of 11 different pressure pain stimuli, and rated each stimulus on a 0-10 scale of intensity. Stimulus distribution was varied between participants. Study 1 found that that the rating of a stimulus of a particular pressure was higher in the context in which it ranked highest. Study 2 found that pain ratings were higher in a context where most stimuli were relatively intense, even when the mean stimulus was constant. It is suggested that pain judgments are relative, involve the same cognitive processes as are used in other psychophysical and socioemotional judgments, and are well described by range frequency theory. This approach can further inform the existing body of research on context-dependent pain evaluation.
Related JoVE Video
Stimulus spacing effects in duration perception are larger for auditory stimuli: Data and a model.
Acta Psychol (Amst)
PUBLISHED: 01-16-2013
Show Abstract
Hide Abstract
Models of duration bisection have focused on the effects of stimulus spacing and stimulus modality. However, interactions between stimulus spacing and stimulus modality have not been examined systematically. Two duration bisection experiments that address this issue are reported. Experiment 1 showed that stimulus spacing influenced the classification of auditory, but not visual, stimuli. Experiment 2 used a wider stimulus range, and showed stimulus spacing effects for both visual and auditory stimuli, although the effects were larger for auditory stimuli. A version of Temporal Range Frequency Theory was applied to the data, and was used to demonstrate that the qualitative pattern of results can be captured with the single assumption that the durations of visual stimuli are less discriminable from one another than are the durations of auditory stimuli.
Related JoVE Video
Highly compressed two-dimensional form of water at ambient conditions.
Sci Rep
PUBLISHED: 01-15-2013
Show Abstract
Hide Abstract
The structure of thin-film water on a BaF(2)(111) surface under ambient conditions was studied using x-ray absorption spectroscopy from ambient to supercooled temperatures at relative humidity up to 95%. No hexagonal ice-like structure was observed in spite of the expected templating effect of the lattice-matched (111) surface. The oxygen K-edge x-ray absorption spectrum of liquid thin-film water on BaF(2) exhibits, at all temperatures, a strong resemblance to that of high-density phases for which the observed spectroscopic features correlate linearly with the density. Surprisingly, the highly compressed, high-density thin-film liquid water is found to be stable from ambient (300 K) to supercooled (259 K) temperatures, although a lower-density liquid would be expected at supercooled conditions. Molecular dynamics simulations indicate that the first layer water on BaF(2)(111) is indeed in a unique local structure that resembles high-density water, with a strongly collapsed second coordination shell.
Related JoVE Video
Endogenous purification reveals GREB1 as a key estrogen receptor regulatory factor.
Cell Rep
PUBLISHED: 01-14-2013
Show Abstract
Hide Abstract
Estrogen receptor-? (ER) is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting proteins have been limited. We purified endogenous ER using an approach termed RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins) and discovered the interactome under agonist- and antagonist-liganded conditions in breast cancer cells, revealing transcriptional networks in breast cancer. The most estrogen-enriched ER interactor is GREB1, a potential clinical biomarker with no known function. GREB1 is shown to be a chromatin-bound ER coactivator and is essential for ER-mediated transcription, because it stabilizes interactions between ER and additional cofactors. We show a GREB1-ER interaction in three xenograft tumors, and using a directed protein-protein approach, we find GREB1-ER interactions in half of ER(+) primary breast cancers. This finding is supported by histological expression of GREB1, which shows that GREB1 is expressed in half of ER(+) cancers, and predicts good clinical outcome. These findings reveal an unexpected role for GREB1 as an estrogen-specific ER cofactor that is expressed in drug-sensitive contexts.
Related JoVE Video
Cytosolic phospholipase A(2)? and eicosanoids regulate expression of genes in macrophages involved in host defense and inflammation.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
The role of Group IVA cytosolic phospholipase A2 (cPLA2?) activation in regulating macrophage transcriptional responses to Candida albicans infection was investigated. cPLA2? releases arachidonic acid for the production of eicosanoids. In mouse resident peritoneal macrophages, prostacyclin, prostaglandin E2 and leukotriene C4 were produced within minutes of C. albicans addition before cyclooxygenase 2 expression. The production of TNF? was lower in C. albicans-stimulated cPLA2?(+/+) than cPLA2?(-/-) macrophages due to an autocrine effect of prostaglandins that increased cAMP to a greater extent in cPLA2?(+/+) than cPLA2?(-/-) macrophages. For global insight, differential gene expression in C. albicans-stimulated cPLA2?(+/+) and cPLA2?(-/-) macrophages (3 h) was compared by microarray. cPLA2?(+/+) macrophages expressed 86 genes at lower levels and 181 genes at higher levels than cPLA2?(-/-) macrophages (?2-fold, p<0.05). Several pro-inflammatory genes were expressed at lower levels (Tnf?, Cx3cl1, Cd40, Ccl5, Csf1, Edn1, CxCr7, Irf1, Irf4, Akna, Ifn?, several IFN?-inducible GTPases). Genes that dampen inflammation (Socs3, Il10, Crem, Stat3, Thbd, Thbs1, Abca1) and genes involved in host defense (Gja1, Csf3, Trem1, Hdc) were expressed at higher levels in cPLA2?(+/+) macrophages. Representative genes expressed lower in cPLA2?(+/+) macrophages (Tnf?, Csf1) were increased by treatment with a prostacyclin receptor antagonist and protein kinase A inhibitor, whereas genes expressed at higher levels (Crem, Nr4a2, Il10, Csf3) were suppressed. The results suggest that C. albicans stimulates an autocrine loop in macrophages involving cPLA2?, cyclooxygenase 1-derived prostaglandins and increased cAMP that globally effects expression of genes involved in host defense and inflammation.
Related JoVE Video
Size-controlled dissolution of organic-coated silver nanoparticles.
Environ. Sci. Technol.
PUBLISHED: 12-27-2011
Show Abstract
Hide Abstract
The solubility of Ag NPs can affect their toxicity and persistence in the environment. We measured the solubility of organic-coated silver nanoparticles (Ag NPs) having particle diameters ranging from 5 to 80 nm that were synthesized using various methods, and with different organic polymer coatings including poly(vinylpyrrolidone) and gum arabic. The size and morphology of Ag NPs were characterized by transmission electron microscopy (TEM). X-ray absorption fine structure (XAFS) spectroscopy and synchrotron-based total X-ray scattering and pair distribution function (PDF) analysis were used to determine the local structure around Ag and evaluate changes in crystal lattice parameters and structure as a function of NP size. Ag NP solubility dispersed in 1 mM NaHCO(3) at pH 8 was found to be well correlated with particle size based on the distribution of measured TEM sizes as predicted by the modified Kelvin equation. Solubility of Ag NPs was not affected by the synthesis method and coating as much as by their size. Based on the modified Kelvin equation, the surface tension of Ag NPs was found to be ?1 J/m(2), which is expected for bulk fcc (face centered cubic) silver. Analysis of XAFS, X-ray scattering, and PDFs confirm that the lattice parameter, a, of the fcc crystal structure of Ag NPs did not change with particle size for Ag NPs as small as 6 nm, indicating the absence of lattice strain. These results are consistent with the finding that Ag NP solubility can be estimated based on TEM-derived particle size using the modified Kelvin equation for particles in the size range of 5-40 nm in diameter.
Related JoVE Video
Social norm influences on evaluations of the risks associated with alcohol consumption: applying the rank-based decision by sampling model to health judgments.
Alcohol Alcohol.
PUBLISHED: 11-17-2011
Show Abstract
Hide Abstract
The research first tested whether perceptions of other peoples alcohol consumption influenced drinkers perceptions of the riskiness of their own consumption. Second, the research tested how such comparisons are made-whether, for example, people compare their drinking to the average drinkers or rank their consumption amongst other peoples. The latter untested possibility, suggested by the recent Decision by Sampling Model of judgment, would imply different cognitive mechanisms and suggest that information should be presented differently to people in social norm interventions.
Related JoVE Video
Community duplicate diet methodology: a new tool for estimating dietary exposures to pesticides.
J Environ Monit
PUBLISHED: 11-03-2011
Show Abstract
Hide Abstract
An observational field study was conducted to assess the feasibility of a community duplicate diet collection method; a dietary monitoring tool that is population-based. The purpose was to establish an alternative procedure to duplicate diet sampling that would be more efficient for a large, defined population, e.g., in the National Childrens Study (NCS). Questionnaire data and food samples were collected in a residence so as not to lose the important component of storage, preparation, and handling in a contaminated microenvironment. The participants included nine Hispanic women of child bearing age living in Apopka, FL, USA. Foods highly consumed by Hispanic women were identified based on national food frequency questionnaires and prioritized by permethrin residue concentrations as measured for the Pesticide Data Program. Participants filled out questionnaires to determine if highly consumed foods were commonly eaten by them and to assess the collection protocol for the food samples. Measureable levels of permethrin were found in 54% of the samples. Questionnaire responses indicated that the collection of the community duplicate diet was feasible for a defined population.
Related JoVE Video
Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus.
Infect. Immun.
PUBLISHED: 10-28-2011
Show Abstract
Hide Abstract
We have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility to Aspergillus fumigatus lung infection in the presence of lower interleukin 23 (IL-23) and IL-17A production in the lungs and have reported a role for IL-17A in lung defense. As IL-23 is also thought to control the production of IL-22, we examined the role of Dectin-1 in IL-22 production, as well as the role of IL-22 in innate host defense against A. fumigatus. Here, we show that Dectin-1-deficient mice demonstrated significantly reduced levels of IL-22 in the lungs early after A. fumigatus challenge. Culturing cells from enzymatic lung digests ex vivo further demonstrated Dectin-1-dependent IL-22 production. IL-22 production was additionally found to be independent of IL-1?, IL-6, or IL-18 but required IL-23. The addition of recombinant IL-23 augmented IL-22 production in wild-type (WT) lung cells and rescued IL-22 production by lung cells from Dectin-1-deficient mice. In vivo neutralization of IL-22 in the lungs of WT mice resulted in impaired A. fumigatus lung clearance. Moreover, mice deficient in IL-22 also demonstrated a higher lung fungal burden after A. fumigatus challenge in the presence of impaired IL-1?, tumor necrosis factor alpha (TNF-?), CCL3/MIP-1?, and CCL4/MIP-1? production and lower neutrophil recruitment, yet intact IL-17A production. We further show that lung lavage fluid collected from both A. fumigatus-challenged Dectin-1-deficient and IL-22-deficient mice had compromised anti-fungal activity against A. fumigatus in vitro. Although lipocalin 2 production was observed to be Dectin-1 and IL-22 dependent, lipocalin 2-deficient mice did not demonstrate impaired A. fumigatus clearance. Moreover, lung S100a8, S100a9, and Reg3g mRNA expression was not lower in either Dectin-1-deficient or IL-22-deficient mice. Collectively, our results indicate that early innate lung defense against A. fumigatus is mediated by Dectin-1-dependent IL-22 production.
Related JoVE Video
Neutron pair distribution function study of two-line ferrihydrite.
Environ. Sci. Technol.
PUBLISHED: 10-27-2011
Show Abstract
Hide Abstract
Pair distribution function (PDF) analysis of neutron total scattering data from deuterated two-line ferrihydrite is consistent with the Keggin-related structural model for ferrihydrite published by Michel et al. (2007). Other models proposed in the literature, such as that of Drits et al. (1993), lead to inferior fits. Bond valence sums indicate that O(1) is bonded to a hydrogen atom, but the quality of the data is such that the exact position of the hydrogen could not be elucidated with confidence.
Related JoVE Video
Restoring primacy in amnesic free recall: evidence for the recency theory of primacy.
Cogn Neuropsychol
PUBLISHED: 10-17-2011
Show Abstract
Hide Abstract
Primacy and recency effects at immediate recall are thought to reflect the independent functioning of a long-term memory store (primacy) and a short-term memory store (recency). Key evidence for this theory comes from amnesic patients who show severe long-term memory storage deficits, coupled with profoundly attenuated primacy. Here we challenge this dominant dual-store theory of immediate recall by demonstrating that attenuated primacy in amnesic patients can reflect abnormal working memory rehearsal processes. D.A., a patient with severe amnesia, presented with profoundly attenuated primacy when using her preferred atypical noncumulative rehearsal strategy. In contrast, despite her severe amnesia, she showed normal primacy when her rehearsal was matched with that of controls via an externalized cumulative rehearsal schedule. Our data are in keeping with the "recency theory of primacy" and suggest that primacy at immediate recall is dependent upon medial temporal lobe involvement in cumulative rehearsal rather than long-term memory storage.
Related JoVE Video
Does the brain calculate value?
Trends Cogn. Sci. (Regul. Ed.)
PUBLISHED: 09-24-2011
Show Abstract
Hide Abstract
How do people choose between options? At one extreme, the value-first view is that the brain computes the value of different options and simply favours options with higher values. An intermediate position, taken by many psychological models of judgment and decision making, is that values are computed but that the resulting choices depend heavily on the context of available options. At the other extreme, the comparison-only view argues that choice depends directly on comparisons, with or even without any intermediate computation of value. In this paper, we place past and current psychological and neuroscientific theories on this spectrum, and review empirical data that have led to an increasing focus on comparison rather than value as the driver of choice.
Related JoVE Video
A co-ordinated interaction between CTCF and ER in breast cancer cells.
BMC Genomics
PUBLISHED: 09-13-2011
Show Abstract
Hide Abstract
CCCTC-binding factor (CTCF) is a conserved zinc finger transcription factor that is involved in both intra- and interchromasomal looping. Recent research has shown a role for CTCF in estrogen receptor (ER) biology, at some individual loci, but a multi-context global analysis of CTCF binding and transcription activity is lacking.
Related JoVE Video
C-type lectin receptors and cytokines in fungal immunity.
Cytokine
PUBLISHED: 08-05-2011
Show Abstract
Hide Abstract
Fungi are the cause of opportunistic infections, predominantly in immunocompromised individuals although, primary fungal infections can occur in apparently healthy individuals. Successful host defence requires an effective innate and adaptive immune response. Central to host immune responses are the induction of cytokines; the signals which help to activate the innate immune system and which play a central role in directing the development of pathogen-specific immunity. C-type lectins play a central role in the recognition and shaping of immune responses to fungal pathogens, in part, through the induction and modulation of cytokine responses. Understanding which cytokines induce protective responses to these pathogens and how C-type lectins and other receptors direct cytokine production may allow development of novel antifungal therapies. Here we review the C-type lectins, their influence on cytokine production and subsequent immune responses in antifungal immunity.
Related JoVE Video
Distinctive arsenic(V) trapping modes by magnetite nanoparticles induced by different sorption processes.
Environ. Sci. Technol.
PUBLISHED: 08-02-2011
Show Abstract
Hide Abstract
Arsenic sorption onto iron oxide spinels such as magnetite may contribute to arsenic immobilization at redox fronts in soils, sediments, and aquifers, as well as in putative remediation and water treatment technologies. We have investigated As(V) speciation resulting from different sorption processes on magnetite nanoparticles, including both adsorption and precipitation, using X-ray absorption fine structure (XAFS) spectroscopy and transmission electron microscopy (TEM). XAFS results suggest that AsO(4) tetrahedra form predominantly inner-sphere bidentate corner-sharing ((2)C) complexes and outer-sphere complexes on magnetite in the adsorption experiments. In the precipitation experiments, an increasing fraction of AsO(4) tetrahedra appears to be incorporated in clusters having a magnetite-like local structure with increasing As loading, the remaining fraction of As being adsorbed at the surface of magnetite particles. In the sample with the highest As loading (15.7 ?mol/m(2)) XAFS data indicate that As(V) is fully incorporated in such clusters. Such processes help to explain the significantly higher arsenic uptake in precipitation samples compared to those generated in adsorption experiments. In addition, for the precipitation samples, TEM observations indicate the formation of amorphous coatings and small (~3 nm) nanoparticles associated with larger (~20-40 nm) magnetite nanoparticles, which are absent in the adsorption samples. These results suggest that As(V) could form complexes at the surfaces of the small nanoparticles and could be progressively incorporated in their structure with increasing As loading. These results provide some of the fundamental knowledge about As(V)-magnetite interactions that is essential for developing effective water treatment technologies for arsenic.
Related JoVE Video
Neutrophils produce interleukin 17A (IL-17A) in a dectin-1- and IL-23-dependent manner during invasive fungal infection.
Infect. Immun.
PUBLISHED: 08-01-2011
Show Abstract
Hide Abstract
We have previously reported that compromised interleukin 17A (IL-17A) production in the lungs increased susceptibility to infection with the invasive fungal pathogen Aspergillus fumigatus. Here we have shown that culturing lung cells from A. fumigatus-challenged mice ex vivo demonstrated Dectin-1-dependent IL-17A production. In this system, neutralization of IL-23 but not IL-6, IL-1?, or IL-18 resulted in attenuated IL-17A production. Il23 mRNA expression was found to be lower in lung cells from A. fumigatus-challenged Dectin-1-deficient mice, whereas bone marrow-derived dendritic cells from Dectin-1-deficient mice failed to produce IL-23 in response to A. fumigatus in vitro. Addition of recombinant IL-23 augmented IL-17A production by wild-type (WT) and Dectin-1-deficient lung cells, although the addition of IL-6 or IL-1? did not augment the effect of IL-23. Intracellular cytokine staining of lung cells revealed lower levels of CD11b(+) IL-17A(+) and Ly-6G(+) IL-17A(+) cells in A. fumigatus-challenged Dectin-1-deficient mice. Ly-6G(+) neutrophils purified from the lungs of A. fumigatus-challenged Dectin-1-deficient mice displayed lower Il17a mRNA expression but surprisingly had intact Rorc and Rora mRNA expression. We further demonstrated that Ly-6G(+) neutrophils required the presence of myeloid cells for IL-17A production. Finally, upon in vitro stimulation with A. fumigatus, thioglycolate-elicited peritoneal neutrophils were positive for intracellular IL-17A expression and produced IL-17A in a Dectin-1- and IL-23-dependent manner. In summary, Dectin-1-dependent IL-17A production in the lungs during invasive fungal infection is mediated in part by CD11b(+) Ly-6G(+) neutrophils in an IL-23-dependent manner.
Related JoVE Video
Probing Ag nanoparticle surface oxidation in contact with (in)organics: an X-ray scattering and fluorescence yield approach.
J Synchrotron Radiat
PUBLISHED: 07-29-2011
Show Abstract
Hide Abstract
Characterizing interfacial reactions is a crucial part of understanding the behavior of nanoparticles in nature and for unlocking their functional potential. Here, an advanced nanostructure characterization approach to study the corrosion processes of silver nanoparticles (Ag-Nps), currently the most highly produced nanoparticle for nanotechnology, is presented. Corrosion of Ag-Nps under aqueous conditions, in particular in the presence of organic matter and halide species common to many natural environments, is of particular importance because the release of toxic Ag(+) from oxidation/dissolution of Ag-Nps may strongly impact ecosystems. In this context, Ag-Nps capped with polyvinolpyrrolidone (PVP) in contact with a simple proxy of organic matter in natural waters [polyacrylic acid (PAA) and Cl(-) in solution] has been investigated. A combination of synchrotron-based X-ray standing-wave fluorescence yield- and X-ray diffraction-based experiments on a sample consisting of an approximately single-particle layer of Ag-Nps deposited on a silicon substrate and coated by a thin film of PAA containing Cl revealed the formation of a stable AgCl corrosion product despite the presence of potential surface stabilizers (PVP and PAA). Diffusion and precipitation processes at the Ag-Nps-PAA interface were characterized with a high spatial resolution using this new approach.
Related JoVE Video
Phagocytes: fussy about carbs.
Curr. Biol.
PUBLISHED: 07-12-2011
Show Abstract
Hide Abstract
A new mechanistic model based on the formation of a phagocytic synapse explains how immune cells detect and respond to direct contact with fungal pathogens.
Related JoVE Video
Screening for ligands of C-type lectin-like receptors.
Methods Mol. Biol.
PUBLISHED: 06-25-2011
Show Abstract
Hide Abstract
In order to execute their immune functions, leukocytes interact with a broad range of cell types through cell surface receptors, such as those of the immunoglobulin and C-type lectin families, or indirectly through soluble factors. The characterization of activating and inhibitory counterparts of NK cell receptors on myeloid cells, as well as the identification of their physiological ligands, has provided new insights into the underlying mechanisms of immunity and homeostasis. Here, we describe methodology that can be employed to screen for endogenous ligands of type-II C-type lectin-like receptors using reporter cells and Fc fusion proteins.
Related JoVE Video
Innate antifungal immunity: the key role of phagocytes.
Annu. Rev. Immunol.
PUBLISHED: 06-09-2011
Show Abstract
Hide Abstract
Fungal diseases have emerged as significant causes of morbidity and mortality, particularly in immune-compromised individuals, prompting greater interest in understanding the mechanisms of host resistance to these pathogens. Consequently, the past few decades have seen a tremendous increase in our knowledge of the innate and adaptive components underlying the protective (and nonprotective) mechanisms of antifungal immunity. What has emerged from these studies is that phagocytic cells are essential for protection and that defects in these cells compromise the hosts ability to resist fungal infection. This review covers the functions of phagocytes in innate antifungal immunity, along with selected examples of the strategies that are used by fungal pathogens to subvert these defenses.
Related JoVE Video
An evolutionary based social rank explanation of why low income predicts mental distress: a 17 year cohort study of 30,000 people.
J Affect Disord
PUBLISHED: 05-23-2011
Show Abstract
Hide Abstract
This paper presents a new psychological model of why low income increases risk of mental distress. Consistent with evolutionary perspectives on disorder, income was predicted to relate to mental distress only through acting as an indirect proxy for social rank.
Related JoVE Video
Sulfidation processes of PVP-coated silver nanoparticles in aqueous solution: impact on dissolution rate.
Environ. Sci. Technol.
PUBLISHED: 05-20-2011
Show Abstract
Hide Abstract
Despite the increasing use of silver nanoparticles (Ag-NPs) in nanotechnology and their toxicity to invertebrates, the transformations and fate of Ag-NPs in the environment are poorly understood. This work focuses on the sulfidation processes of PVP-coated Ag-NPs, one of the most likely corrosion phenomena that may happen in the environment. The sulfur to Ag-NPs ratio was varied in order to control the extent of Ag-NPs transformation to silver sulfide (Ag?S). A combination of synchrotron-based X-ray Diffraction (XRD) and Extended X-ray Absorption Fine Structure spectroscopy shows the increasing formation of Ag?S with an increasing sulfur to Ag-NPs ratio. TEM observations show that Ag?S forms nanobridges between the Ag-NPs leading to chain-like structures. In addition, sulfidation strongly affects surface properties of the Ag-NPs in terms of surface charge and dissolution rate. Both may affect the reactivity, transport, and toxicity of Ag-NPs in soils. In particular, the decrease of dissolution rate as a function of sulfide exposure may strongly limit Ag-NPs toxicity since released Ag? ions are known to be a major factor in the toxicity of Ag-NPs.
Related JoVE Video
Transducin-like enhancer protein 1 mediates estrogen receptor binding and transcriptional activity in breast cancer cells.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-02-2011
Show Abstract
Hide Abstract
Estrogen receptor (ER) binds to distal enhancers within the genome and requires additional factors, such as the Forkhead protein FoxA1, for mediating chromatin interactions. We now show that the human Groucho protein, Transducin-like enhancer protein 1 (TLE1), positively assists some ER-chromatin interactions, a role that is distinct from its general role as a transcriptional repressor. We show that specific silencing of TLE1 inhibits the ability of ER to bind to a subset of ER binding sites within the genome, a phenomenon that results in perturbations in phospho-RNA Pol II recruitment. Furthermore, TLE1 is essential for effective ER-mediated cell division. We have discovered a distinct role for TLE1, as a necessary transcriptional component of the ER complex, where it facilitates ER-chromatin interactions.
Related JoVE Video
Pesticides on household surfaces may influence dietary intake of children.
Environ. Sci. Technol.
PUBLISHED: 04-25-2011
Show Abstract
Hide Abstract
The physical and chemical environment influences childrens exposures to pesticides in and around the home. Childrens activities, which increase their potential for exposure especially during eating, have been captured in the Childrens Dietary Intake Model (CDIM). In addition to the chemical exposure associated with the food itself, this model incorporates excess dietary exposures due to handling of food during consumption. To stochastically evaluate CDIM, distributions of measured, and in some cases estimated, model factors were determined from measurements of permethrin, chlorpyrifos, and diazinon derived from assembled databases and laboratory experiments. Using the distributions of these factors, Monte Carlo simulations were performed to obtain distributions of total dietary intake of pesticides. To target the sources of pesticide contamination that were influencing total dietary intake, each factor was evaluated. We found pesticide surface concentration to be highly influential. By excluding surface concentration, we were also able to determine the influence of the other factors based on the F-statistic. Transfer efficiencies, followed by pesticide residue in consumed foods and amount of food consumed, were the next most influential factors within the model. With these distributions for model inputs, CDIM has the potential to more accurately predict total dietary intake of a contaminant by a child.
Related JoVE Video
The role of Dectin-1 in the host defence against fungal infections.
Curr. Opin. Microbiol.
PUBLISHED: 04-08-2011
Show Abstract
Hide Abstract
Dectin-1 is an innate immune pattern recognition receptor (PRR) that, through its ability to bind ?-glucans, is involved in the recognition of several pathogenic fungi. Dectin-1 can stimulate a variety of cellular responses via the Syk/CARD9 signalling pathway, including phagocytosis, cytokine production and the respiratory burst. Several advances in our understanding of Dectin-1 immunobiology have been made in recent years, including characterisation of additional signalling pathways and demonstration of its ability to directly induce the development of adaptive immunity. However, the physiological role of many of the functions of this receptor is still unclear. This review aims to provide an update on Dectin-1 and its role within antifungal immune responses, focussing on progress made in the last two years.
Related JoVE Video
Expression of the hMICL in acute myeloid leukemia-a highly reliable disease marker at diagnosis and during follow-up.
Cytometry B Clin Cytom
PUBLISHED: 04-01-2011
Show Abstract
Hide Abstract
Stable flow cytometric markers for malignant myeloid cells are highly warranted. Based on data from stem cell research, we hypothesized that the human inhibitory C-type lectin like receptor (hMICL) might represent a novel diagnostic and prognostic vehicle in a standard flow cytometry (FCM) setting.
Related JoVE Video
Study of the crystallographic architecture of corals at the nanoscale by scanning transmission X-ray microscopy and transmission electron microscopy.
Ultramicroscopy
PUBLISHED: 03-26-2011
Show Abstract
Hide Abstract
We have investigated the nanotexture and crystallographic orientation of aragonite in a coral skeleton using synchrotron-based scanning transmission X-ray microscopy (STXM) and transmission electron microscopy (TEM). Polarization-dependent STXM imaging at 40-nm spatial resolution was used to obtain an orientation map of the c-axis of aragonite on a focused ion beam milled ultrathin section of a Porites coral. This imaging showed that one of the basic units of coral skeletons, referred to as the center of calcification (COC), consists of a cluster of 100-nm aragonite globules crystallographically aligned over several micrometers with a fan-like distribution and with the properties of single crystals at the mesoscale. The remainder of the skeleton consists of aragonite single-crystal fibers in crystallographic continuity with the nanoglobules comprising the COC. Our observation provides information on the nm-scale processes that led to biomineral formation in this sample. Importantly, the present study illustrates how the methodology described here, which combines HRTEM and polarization-dependent synchrotron-based STXM imaging, offers an interesting new approach for investigating biomineralizing systems at the nm-scale.
Related JoVE Video
Human papillomavirus testing in men.
J Am Osteopath Assoc
PUBLISHED: 03-19-2011
Show Abstract
Hide Abstract
Despite the morbidity associated with anogenital condylomas and the mortality associated with anal, penile, and cervical carcinoma as a direct consequence of human papillomavirus (HPV), the US Centers for Disease Control and Prevention currently does not recommend routine screening for HPV in immuno competent men. However, findings of emerging research focusing on the high-risk populations of men who have sex with men and men who test positive for human immunodeficiency virus, in whom HPV infection is pervasive and persistent, suggest that these populations may benefit from screening. Therefore, HPV screening, including anal cytology, should be considered for these men in settings where appropriate follow-up, including high-resolution anoscopy, is available.
Related JoVE Video
Thanks, but Im used to better: a relative rank model of gratitude.
Emotion
PUBLISHED: 03-16-2011
Show Abstract
Hide Abstract
We argue that more help does not necessarily lead to more gratitude. Rather, gratitude depends on how a given instance of help compares with the help that a person is used to receiving. Participants read vignettes detailing an event in which 11 different friends either lent them varying amounts of money or spent varying amounts of time providing help. The amount of gratitude elicited by a given amount of help (e.g., a loan of £36 [about $56] or 49 min help) differed substantially depending on how this amount ranked among the help they were getting from their other friends. Comparison across four experimental conditions suggested that these judgments operated via the same general cognitive mechanisms used to judge other social events and psychophysical stimuli (as outlined by range frequency theory). Although more help does lead to more gratitude, people appear to be sensitive to how that help compares with what others are providing, and experienced gratitude depends on these relative judgments.
Related JoVE Video
Control of solid-state lasers using an intra-cavity MEMS micromirror.
Opt Express
PUBLISHED: 03-04-2011
Show Abstract
Hide Abstract
High reflectivity, electrothermal and electrostatic MEMS (Micro-Electro-Mechanical Systems) micromirrors were used as a control element within a Nd-doped laser cavity. Stable continuous-wave oscillation of a 3-mirror Nd:YLF laser at a maximum output power of 200 mW was limited by thermally-induced surface deformation of the micromirror. An electrostatic micromirror was used to induce Q-switching, resulting in pulse durations of 220 ns - 2 ?s over a repetition frequency range of 6 kHz - 40 kHz.
Related JoVE Video
In vivo functional analysis and genetic modification of in vitro-derived mouse neutrophils.
FASEB J.
PUBLISHED: 03-02-2011
Show Abstract
Hide Abstract
Mature neutrophils are notoriously short-lived immune cells that cannot be genetically manipulated. Analysis of gene function therefore requires genetically modified animals, which is expensive, time-consuming, and costly in animal life. Analysis of gene function in neutrophils in a physiologically relevant context thus represents a significant problem in the field. We sought to overcome this obstruction in the field by developing a strategy for the analysis of gene function in neutrophils in a physiologically relevant context. Here, we demonstrate the functional relevance of in vitro conditional-Hoxb8 immortalized precursor-derived neutrophils. In vitro-derived neutrophils functionally resembled primary neutrophils, but critically, neutrophils generated in this way can be adoptively transferred into live animals and tracked during inflammatory responses using single-cell analysis to define functional attributes. We have validated this approach using CD11b-deficient neutrophils and replicated the key findings observed in gene-targeted animals and in naturally CD11b-deficient humans. Furthermore, we show that by retroviral transduction, one can generate stable alterations in the precursor cell lines and thus a continuous supply of functionally altered neutrophils. This novel technological advance offers for the first time the possibility of applying higher-throughput genetic modification and in vivo functional analysis to the neutrophil-lineage.
Related JoVE Video
Restoration of pattern recognition receptor costimulation to treat chromoblastomycosis, a chronic fungal infection of the skin.
Cell Host Microbe
PUBLISHED: 02-28-2011
Show Abstract
Hide Abstract
Chromoblastomycosis is a chronic skin infection caused by the fungus Fonsecaea pedrosoi. Exploring the reasons underlying the chronic nature of F. pedrosoi infection in a murine model of chromoblastomycosis, we find that chronicity develops due to a lack of pattern recognition receptor (PRR) costimulation. F. pedrosoi was recognized primarily by C-type lectin receptors (CLRs), but not by Toll-like receptors (TLRs), which resulted in the defective induction of proinflammatory cytokines. Inflammatory responses to F. pedrosoi could be reinstated by TLR costimulation, but also required the CLR Mincle and signaling via the Syk/CARD9 pathway. Importantly, exogenously administering TLR ligands helped clear F. pedrosoi infection in vivo. These results demonstrate how a failure in innate recognition can result in chronic infection, highlight the importance of coordinated PRR signaling, and provide proof of the principle that exogenously applied PRR agonists can be used therapeutically.
Related JoVE Video
Recognition and blocking of innate immunity cells by Candida albicans chitin.
Infect. Immun.
PUBLISHED: 02-28-2011
Show Abstract
Hide Abstract
Chitin is a skeletal cell wall polysaccharide of the inner cell wall of fungal pathogens. As yet, little about its role during fungus-host immune cell interactions is known. We show here that ultrapurified chitin from Candida albicans cell walls did not stimulate cytokine production directly but blocked the recognition of C. albicans by human peripheral blood mononuclear cells (PBMCs) and murine macrophages, leading to significant reductions in cytokine production. Chitin did not affect the induction of cytokines stimulated by bacterial cells or lipopolysaccharide (LPS), indicating that blocking was not due to steric masking of specific receptors. Toll-like receptor 2 (TLR2), TLR4, and Mincle (the macrophage-inducible C-type lectin) were not required for interactions with chitin. Dectin-1 was required for immune blocking but did not bind chitin directly. Cytokine stimulation was significantly reduced upon stimulation of PBMCs with heat-killed chitin-deficient C. albicans cells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.