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Find video protocols related to scientific articles indexed in Pubmed.
Negative regulation of the interferon response by an interferon-induced long non-coding RNA.
Nucleic Acids Res.
PUBLISHED: 08-13-2014
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Long non-coding RNAs (lncRNAs) play critical roles in diverse cellular processes; however, their involvement in many critical aspects of the immune response including the interferon (IFN) response remains poorly understood. To address this gap, we compared the global gene expression pattern of primary human hepatocytes before and at three time points after treatment with IFN-?. Among ? 200 IFN-induced lncRNAs, one transcript showed ? 100-fold induction. This RNA, which we named lncRNA-CMPK2, was a spliced, polyadenylated nuclear transcript that was induced by IFN in diverse cell types from human and mouse. Similar to protein-coding IFN-stimulated genes (ISGs), its induction was dependent on JAK-STAT signaling. Intriguingly, knockdown of lncRNA-CMPK2 resulted in a marked reduction in HCV replication in IFN-stimulated hepatocytes, suggesting that it could affect the antiviral role of IFN. We could show that lncRNA-CMPK2 knockdown resulted in upregulation of several protein-coding antiviral ISGs. The observed upregulation was caused by an increase in both basal and IFN-stimulated transcription, consistent with loss of transcriptional inhibition in knockdown cells. These results indicate that the IFN response involves a lncRNA-mediated negative regulatory mechanism. lncRNA-CMPK2 was strongly upregulated in a subset of HCV-infected human livers, suggesting a role in modulation of the IFN response in vivo.
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Influence of hepatitis C virus coinfection on CD4? T cells of HIV-infected patients receiving HAART.
AIDS
PUBLISHED: 08-12-2014
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The effects of hepatitis C virus (HCV) coinfection on immune homeostasis and immune restoration in treated HIV infection are not well understood.
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Ventilator associated pneumonia in major paediatric burns.
Burns
PUBLISHED: 01-25-2014
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More than three-quarters of deaths related to major burns are a consequence of infection, which is frequently ventilator associated pneumonia (VAP). A retrospective study was performed, over a five-year period, of ventilated children with major burns. 92 patients were included in the study; their mean age was 3.5 years and their mean total body surface area burn was 30%. 62% of the patients sustained flame burns, and 31% scalds. The mean ICU stay was 10.6 days (range 2-61 days) and the mean ventilation time was 8.4 days (range 2-45 days). There were 59 documented episodes of pneumonia in 52 patients with a rate of 30 infections per 1000 ventilator days. Length of ventilation and the presence of inhalational injury correlate with the incidence of VAP. 17.4% of the patients died (n=16); half of these deaths may be attributed directly to pneumonia. Streptococcus pneumonia, Pseudomonas aeruginosa, Acinetobacter baumanii and Staphylococcus aureus were the most prominent aetiological organisms. Broncho-alveolar lavage was found to be more specific and sensitive at identifying the organism than other methods. This study highlights the importance of implementing strictly enforced strategies for the prevention, detection and management of pneumonia in the presence of major burns.
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Older age is associated with peripheral blood expansion of naïve B cells in HIV-infected subjects on antiretroviral therapy.
PLoS ONE
PUBLISHED: 01-01-2014
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Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (?45 vs. ?30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p?=?0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p?=?0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.
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Specific structure and unique function define the hemicentin.
Cell Biosci
PUBLISHED: 04-24-2013
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Hemicentin has come a long way from when it was first identified in C. elegans as him-4 (High incidence of males). The protein is now a recognized player in maintaining the architectural integrity of vertebrate tissues and organs. Highly conserved hemicentin sequences across species indicate this genes ancient evolutionary roots and functional importance. In mouse, hemicentin is liberally distributed on the cell surface of many cell types, including epithelial cells, endothelial cells of the eye, lung, and uterus, and trophectodermal cells of blastocyst. Recent discoveries have uncovered yet another vital purpose of hemicentin 1. The protein also serves a unique function in mitotic cytokinesis, during which this extracellular matrix protein plays a key role in cleavage furrow maturation. Though understanding of hemicentin function has improved through new discoveries, much about this protein remains mysterious.
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Plasma proteome analysis reveals overlapping, yet distinct mechanisms of immune activation in chronic HCV and HIV infections.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 03-20-2013
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HIV infection contributes to accelerated rates of progression of liver fibrosis during hepatitis C virus (HCV) infection, and HCV liver disease contributes to mortality during HIV infection. Although mechanisms underlying these interactions are not well known, soluble and cellular markers of immune activation associate with disease progression during both infections.
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Rescue of MHC-1 antigen processing machinery by down-regulation in expression of IGF-1 in human glioblastoma cells.
PLoS ONE
PUBLISHED: 02-05-2013
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Escape from immune recognition has been hypothesized to be a factor in carcinogenesis. It may be mediated for many cancers through down-regulation in the MHC class 1 antigen processing and presentation pathway. TAP-1, TAP-2, tightly linked to LMP-2 and LMP-7 are multiple components of the endogenous, antigen presentation pathway machinery. We addressed the question of alterations in this pathway in human Glioblastoma (HGB) and of its relationship to modulation in expression of IGF-1 that is highly expressed in this cancer. Deficiencies in expression of TAP-1 were demonstrated by RT-PCR and/or by immuno-flow cytometry in the HGB cell line T98G obtained from ATCC, and in 3 of 4 human cell lines established from patients with Glioblastoma Multiforme. Deficiencies in expression of TAP-2 were observed in 3 of 4, deficiencies in expression of LMP-2 in 4 of 4 and deficiencies in LMP-7 in 3 of 4 HGB cell lines examined by RT-PCR and Western blot. Following down-regulation of IGF-1 by transfection with the pAnti IGF-1 vector that expresses IGF-1 RNA in antisense orientation, or by the exogenous addition of IGF-1 receptor monoclonal antibody to cell culture media, the deficiencies in components of the MHC-1 antigen presentation pathway were up-regulated and/or rescued in all HGB cell lines tested. Moreover, this up-regulation in expression was aborted by addition of 100 ng/ml of IGF-1 to the culture media. Unlike in the case of IFN-?, the restoration of TAP-1 and LMP-2 by down-regulation of IGF-1 in Glioblastoma cells was not correlated to the tyrosine phosphorylation of STAT 1. In summary, the simultaneous reversion in expression of the multiple constituents of MHC-1 antigen processing path and up-regulation in expression of MHC-1 occurring with down-regulation in IGF-1 may have a role in reinforcement of immunity against tumor antigen(s) in some animal cancers and in humans with Glioblastoma Multiforme.
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Interferon-? is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers.
PLoS ONE
PUBLISHED: 01-10-2013
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Type-I interferon (IFN-I) has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR. Furthermore, we measured the effect of therapeutic administration of IFN? in HCV-infected subjects to model the effect of IFN? on chronic immune activation. IFN-I bioactivity was significantly increased in plasma of untreated HIV-1-infected subjects relative to uninfected subjects (p = 0.012), and IFN? was the predominant IFN-I subtype correlating with IFN-I bioactivity (r = 0.658, p<0.001). IFN? was not detectable in plasma of subjects receiving anti-retroviral therapy. Elevated expression of IFN? mRNA was limited to lymph node tissue cells, suggesting that peripheral blood leukocytes are not a major source of IFN? in untreated chronic HIV-1 infection. Plasma IFN-I levels correlated inversely with CD4 T cell count (p = 0.003) and positively with levels of plasma HIV-1 RNA and CD38 expression on CD8 T cells (p = 0.009). In hepatitis C virus-infected subjects, treatment with IFN-I and ribavirin increased expression of CD38 on CD8 T cells (p = 0.003). These studies identify IFN? derived from lymph nodes, rather than blood leukocytes, as a possible source of the IFN-I signature that contributes to immune activation in HIV-1 infection.
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Soluble biomarkers of HIV transmission, disease progression and comorbidities.
Curr Opin HIV AIDS
PUBLISHED: 01-01-2013
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The purpose of this study is to survey and synthesize recent progress in soluble biomarkers relevant to HIV-1 disease stages, progression and comorbidities.
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A quantitative proteomic approach for detecting protein profiles of activated human myeloid dendritic cells.
J. Immunol. Methods
PUBLISHED: 06-17-2011
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Dendritic cells (DC) direct the magnitude, polarity and effector function of the adaptive immune response. DC express toll-like receptors (TLR), antigen capturing and processing machinery, and costimulatory molecules, which facilitate innate sensing and T cell activation. Once activated, DC can efficiently migrate to lymphoid tissue and prime T cell responses. Therefore, DC play an integral role as mediators of the immune response to multiple pathogens. Elucidating the molecular mechanisms involved in DC activation is therefore central in gaining an understanding of host response to infection. Unfortunately, technical constraints have limited system-wide omic analysis of human DC subsets collected ex vivo. Here we have applied novel proteomic approaches to human myeloid dendritic cells (mDCs) purified from 100 mL of peripheral blood to characterize specific molecular networks of cell activation at the individual patient level, and have successfully quantified over 700 proteins from individual samples containing as little as 200,000 mDCs. The proteomic and network readouts after ex vivo stimulation of mDCs with TLR3 agonists are measured and verified using flow cytometry.
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Systemic immune activation in HIV infection is associated with decreased MDC responsiveness to TLR ligand and inability to activate naive CD4 T-cells.
PLoS ONE
PUBLISHED: 03-15-2011
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HIV infection is characterized by ineffective anti-viral T-cell responses and impaired dendritic cell (DC) functions, including response to Toll-Like Receptor (TLR) ligands. Because TLR responsiveness may affect a hosts response to virus, we examined TLR ligand induced Myeloid and Plasmacytoid DC (MDC and PDC) activation of naïve T-cells in HIV+ subjects.
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Reduced naive CD4 T cell numbers and impaired induction of CD27 in response to T cell receptor stimulation reflect a state of immune activation in chronic hepatitis C virus infection.
J. Infect. Dis.
PUBLISHED: 01-10-2011
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Chronic hepatitis C virus (HCV) infection is characterized by reduced numbers of functional HCV-specific T cells. In addition, chronically HCV-infected individuals have reduced response to vaccine. Alterations in naive CD4 T cell phenotype or function may contribute to these immune impairments.
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Determinants of protection among HIV?exposed seronegative persons: an overview.
J. Infect. Dis.
PUBLISHED: 10-05-2010
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Both clinical experience and a growing medical literature indicate that some persons who have been exposed to human immunodeficiency virus (HIV) infection remain uninfected. Although in some instances this may represent good fortune, cohorts of uninfected persons have been reported who are considered at high risk for infection. In these cohorts a variety of characteristics have been proposed as mediating protection, but to date only the 32–base pair deletion in the chemokine (C‐C motif) receptor 5 gene, which results in complete failure of cell surface expression of this coreceptor, has been associated with high‐level protection from HIV infection. With this in mind, there are probably many other factors that may individually or in combination provide some level of protection from acquisition of HIV infection. Because some of these factors are probably incompletely protective or inconsistently active, identifying them with confidence will be difficult. Nonetheless, clarifying the determinants of protection against HIV infection is a high priority that will require careful selection of high‐risk uninfected cohorts, who should undergo targeted studies of plausible mediators and broad screening for unexpected determinants of protection.
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Peripheral blood B cell subset skewing is associated with altered cell cycling and intrinsic resistance to apoptosis and reflects a state of immune activation in chronic hepatitis C virus infection.
J. Immunol.
PUBLISHED: 07-23-2010
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Chronic hepatitis C virus (HCV) infection is associated with B cell activation, although underlying mechanisms are unclear. To investigate B cell regulation during HCV infection, we measured bulk B cell CpG and Staphylococcus aureus Cowan-induced IgG Ab-secreting cell (ASC) frequency, HCV and tetanus-specific ASC frequency, BCR- and CD40L-dependent CD80/CD86 expression, and activation of memory CD4 cells. Immature transitional, naive, resting memory, mature activated, tissue-like memory, and plasma B cell subset frequencies, cell cycling, and intrinsic apoptosis were quantified. We observed intact or enhanced tetanus-specific and total IgG ASC frequency, serum IgG, BCR- and CD40L-dependent CD80/CD86 expression, and CD40L-dependent bulk B cell activation of memory CD4 cells in HCV infection. HCV-specific ASCs were observed in HCV-infected but not control subjects, although frequencies were lower compared with tetanus-specific cells. Immature transitional and mature activated B cell subset frequencies were increased in HCV-infected subjects, with immature transitional frequency associated with liver inflammation and serum B cell-activating factor. Mature activated B cells less commonly expressed Ki67, more commonly expressed Bcl2, and were more intrinsically resistant to apoptosis, whereas immature transitional B cells more commonly expressed Ki67, the latter associated with plasma HCV level. Taken together, these results indicate that in the setting of chronic HCV infection, a state of activation results in B cell subset skewing that is likely the result of alterations in homeostasis, cell cycling, and intrinsic resistance to apoptosis and that results in an overall intact or enhanced B cell response to BCR and CD40L.
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Impaired plasmacytoid dendritic cell (PDC)-NK cell activity in viremic human immunodeficiency virus infection attributable to impairments in both PDC and NK cell function.
J. Virol.
PUBLISHED: 08-19-2009
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Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections impair plasmacytoid dendritic cell (PDC) and natural killer (NK) cell subset numbers and functions, though little is known about PDC-NK cell interactions during these infections. We evaluated PDC-dependent NK cell killing and gamma interferon (IFN-gamma) and granzyme B production, using peripheral blood mononuclear cell (PBMC)-based and purified cell assays of samples from HCV- and HIV-infected subjects. CpG-enhanced PBMC killing and IFN-gamma and granzyme B activity (dependent on PDC and NK cells) were impaired in viremic HIV infection. In purified PDC-NK cell culture experiments, CpG-enhanced, PDC-dependent NK cell activity was cell contact and IFN-alpha dependent, and this activity was impaired in viremic HIV infection but not in HCV infection. In heterologous PDC-NK cell assays, impaired PDC-NK cell killing activity was largely attributable to an NK cell defect, while impaired PDC-NK cell IFN-gamma-producing activity was attributable to both PDC and NK cell defects. Additionally, the response of NK cells to direct IFN-alpha stimulation was defective in viremic HIV infection, and this defect was not attributable to diminished IFN-alpha receptor expression, though IFN-alpha receptor and NKP30 expression was closely associated with killer activity in viremic HIV infection but not in healthy controls. These data indicate that during uncontrolled HIV infection, PDC-dependent NK cell function is impaired, which is in large part attributable to defective IFN-alpha-induced NK cell activity and not to altered IFN-alpha receptor, NKP30, NKP44, NKP46, or NKG2D expression.
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Differential effects of hepatitis C virus JFH1 on human myeloid and plasmacytoid dendritic cells.
J. Virol.
PUBLISHED: 03-18-2009
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Dendritic cells (DCs) are reported to be functionally deficient during chronic hepatitis C virus (HCV) infection. Differing results have been reported on direct effects of intact replicative-form HCV on DC function. To better understand the effect of HCV on DC function, we treated freshly purified human myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) with HCV JFH1. We found that HCV upregulated mDC maturation marker (CD83, CD86, and CD40) expression and did not inhibit Toll-like receptor 3 (TLR3) ligand [poly(I:C)]-induced mDC maturation, a finding consistent with the phenotype of DCs from HCV-infected subjects. At the same time, HCV JFH1 inhibited the ability of poly(I:C)-treated mDCs to activate naive CD4 T cells. In contrast, although there was no direct effect of virus on pDC maturation, HCV JFH1 inhibited TLR7 ligand (R848)-induced pDC CD40 expression, and this was associated with impaired ability to activate naive CD4 T cells. Parallel experiments with recombinant HCV proteins indicated HCV core protein may be responsible for a portion of the activity. Furthermore, HCV-mediated mDC maturation was dependent upon CD81-E2 interaction and, in part, TLR2. Using UV-treated HCV, we show that HCV-mediated mDC and pDC maturation is virus replication independent and, using strand specific PCR, we found no evidence for HCV replication within DCs. Because these effects of HCV on DC subset maturation and function in part recapitulate direct ex vivo analysis of DCs in chronic HCV infection, the mechanisms described here likely account for a portion of the DC subset defects observed in vivo.
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Accessory cell dependent NK cell mediated PBMC IFN-gamma production is defective in HIV infection.
Clin. Immunol.
PUBLISHED: 02-03-2009
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HCV and HIV infections impair dendritic cell function. We evaluated the impact of HCV, HIV, and HCV-HIV infection on MDC-NK interactions by analyzing CD3 depleted PBMC for NK cell IFN-gamma in response to IL-12 or poly (I:C). Purified MDC and NK cells were analyzed for TLR ligand-dependent, MDC-dependent NK activity. In HIV infection, IFN-gamma production by CD3 depleted PBMC was reduced in response to poly (I:C), while response to IL-12 was intact in HCV and HIV infections. Poly (I:C) induced activity was dependent on MDC and partially dependent on IL-12, consistent with accessory cell help. In purified MDC-NK co-cultures, MDC dependent NK IFN-gamma and Granzyme B was intact in both HCV and HIV infections, while MDC numerical defects were observed in HIV infection. These data indicate that during viral infection with HIV, accessory cell dependent NK function in the periphery is impaired. This impairment may be related to the identified MDC numerical defect.
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Baseline levels of soluble CD14 and CD16+56- natural killer cells are negatively associated with response to interferon/ribavirin therapy during HCV-HIV-1 coinfection.
J. Infect. Dis.
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Disease progression of human immunodeficiency virus type 1 (HIV-1) is associated with immune activation. Activation indices are higher during coinfection of hepatitis C virus (HCV) and HIV. The effect of immune activation on interferon ? (IFN-?) therapy response is unknown. We evaluated soluble CD14 (sCD14) and natural killer (NK)-cell subsets at baseline, and during pegIFN-?2a/ribavirin therapy in HCV-HIV coinfection. The sCD14 level increased during therapy. Baseline sCD14 positively correlated with baseline HCV level and CD16(+)56(-) NK-cell frequency, and both sCD14 and CD16(+)56(-) NK cells correlated negatively with magnitude of HCV decline. IL28B genotype was associated with therapy response but not sCD14 or CD16(+)56(-) NK frequency. Markers of innate immune activation predict poor host response to IFN-?-based HCV therapy during HCV-HIV coinfection.
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Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours.
Chemother Res Pract
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The aim of this study was to establish the criteria for methodology of cellular "anti-IGF-I" therapy of malignant tumours and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and chemotherapy was followed by subcutaneous injection of autologous cancer cells transfected by IGF-I antisense/triple helix expression vectors. The prepared cell "vaccines" should it be in the case of glioblastomas or other tumours, have shown a change of phenotype, the absence of IGF-I protein, and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells, removed after each of two successive vaccinations, have demonstrated for all the types of tumour tested an increasing level of CD8(+) and CD8(+)28(+) molecules and a switch from CD8(+)11b(+) to CD8(+)11. All cancer patients were supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients. The obtained results have permitted to specify the common criteria for "anti-IGF-I" strategy: characteristics sine qua non of injected "vaccines" (cloned cells IGF-I(-) and MHC-I(+)) and of PBL cells (CD8(+) increased level).
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Genetically associated CD16(+)56(-) natural killer cell interferon (IFN)-?R expression regulates signaling and is implicated in IFN-?-induced hepatitis C virus decline.
J. Infect. Dis.
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Natural killer (NK) cells likely contribute to outcome of acute hepatitis C virus (HCV) infection and interferon (IFN)-induced control of chronic HCV infection. We previously observed IFN-?R and NKp30 expression associated with IFN-?-dependent NK cell activity.
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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.

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

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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.