Effect of CCR5-Δ32 Heterozygosity on HIV-1 Susceptibility: A Meta-Analysis

So far, many studies have investigated the distribution of CCR5 genotype between HIV-1 infected patients and uninfected people. However, no definite results have been put forward about whether heterozygosity for a 32-basepair deletion in CCR5 gene (CCR5-Δ32) can affect HIV-1 susceptibility.We performed a meta-analysis of 18 studies including more than 12000 subjects for whom the CCR5-Δ32 polymorphism was genotyped. Odds ratio (OR) with 95% confidence interval (CI) were employed to assess the association of CCR5-Δ32 polymorphism with HIV-1 susceptibility.Compared with the wild-type CCR5 homozygotes, the pooled OR for CCR5-Δ32 heterozygotes was 1.02 (95%CI, 0.88–1.19) for healthy controls (HC) and 0.95 (95%CI, 0.71–1.26) for exposed uninfected (EU) controls. Similar results were found in stratified analysis by ethnicity, sample size and method of CCR5-Δ32 genotyping.The meta-analysis indicated that HIV-1 susceptibility is not significantly affected by heterozygosity for CCR5-Δ32

Mutational Analysis of Highly Conserved Residues in the Phage PhiC31 Integrase Reveals Key Amino Acids Necessary for the DNA Recombination

Background: Amino acid sequence alignment of phage phiC31 integrase with the serine recombinases family revealed highly conserved regions outside the catalytic domain. Until now, no system mutational or biochemical studies have been carried out to assess the roles of these conserved residues in the recombinaton of phiC31 integrase. Methodology/Principal Findings: To determine the functional roles of these conserved residues, a series of conserved residues were targeted by site-directed mutagenesis. Out of the 17 mutants, 11 mutants showed impaired or no recombination ability, as analyzed by recombination assay both in vivo and in vitro. Results of DNA binding activity assays showed that mutants (R18A, I141A, L143A,E153A, I432A and V571A) exhibited a great decrease in DNA binding affinity, and mutants (G182A/F183A, C374A, C376A/G377A, Y393A and V566A) had completely lost their ability to bind to the specific target DNA attB as compared with wild-type protein. Further analysis of mutants (R18A, I141A, L143A and E153A) synapse and cleavage showed that these mutants were blocked in recombination at the stage of strand cleavage. Conclusions/Significance: This data reveals that some of the highly conserved residues both in the N-terminus and C-terminus region of phiC31 integrase, play vital roles in the substrate binding and cleavage. The cysteine-rich motif and th

CCL3L1 Copy Number Variation and Susceptibility to HIV-1 Infection: A Meta-Analysis

Background: Although several studies have investigated whether CCL3L1 copy number variation (CNV) influences the risk of HIV-1 infection, there are still no clear conclusions. Therefore, we performed a meta-analysis using two models to generate a more robust estimate of the association between CCL3L1 CNV and susceptibility to HIV-1 infection. Methods: We divided the cases and controls into two parts as individuals with CCL3L1 gene copy number (GCN) above the population specific median copy number (PMN) and individuals with CCL3L1 GCN below PMN, respectively. Odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were given for the main analysis. We also conducted stratified analyses by ethnicity, age group and sample size. Relevant literatures were searched through PubMed and ISI Web of Knowledge up t

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Function of tumor necrosis factor alpha before and after mutation in gastric cancer

Purpose: To explore the cause of functional changes of tumor necrosis factor alpha (TNF-α) in development of gastric cancer through the structural changes of each site in TNF-α before and after mutation. Methods: Three typical mutant sites (TNF-α-308G/A, 857C/T and 863C/A of TNF-α) were chosen and methods like ab initio modeling was adopted for 3D modeling of TNF-α before and after mutation, besides, the structural changes were also analyzed. Results: Mutation of TNF-α-308G/A led to the production of multiple helical structures and that of 863C/A caused the production of one helical structure in its adjacent region. Mutation of 857C/T, however, did not cause the change in the basic structure of TNF-α. Conclusions: Structural changes of TNF-α may have a significant effect on development of gastric cancer

Visual Object Categorization via Sparse Representation

International audienceIn this paper, we consider the problem of classifying a real world image to the corresponding object class based on its visual content via sparse representation, which is originally used as a powerful tool for acquiring, representing and compressing high-dimensional signals. Assuming the intuitive hypothesis that an image could be represented by a linear combination of the training images from the same class, we propose a novel approach for visual object categorization in which a sparse representation of the image is first of all obtained by solving a l1 or l0-minimization problem and then fed into a traditional classifier such as Support Vector Machine (SVM) to finally perform the specified task. Experimental results obtained on the SIMPLIcity database have shown that this new approach can improve the classification performance compared to standard SVM using directly features extracted from the image

Visual object recognition using multi-scale local binary patterns and line segment feature

International audienceVisual content description is a key issue for machine-based visual objectrecognition, which is one of the most challenging problems in computer vision, dueto intra-class variations and inter-class similarities. A good visual descriptor should bediscriminative enough and computationally efficient while displaying some propertiesof robustness to variations. The recent literature has featured local appearance-basedfeatures, e.g. SIFT, as the main trend because of their great discriminative power. Inthis paper, we propose to adopt two different kinds of feature to characterize differentaspects of object appearance. The first is multi-scale local binary pattern (LBP) operator,which is extracted from coarse-to-fine image blocks to well describe texture structureswhile keeping its computational efficiency. The second is line segment feature, which isbased on Gestalt-inspired region segmentation and fast Hough transform, and aims atcapturing accurate geometric information of visual objects. The experimental results onthe SIMPLIcity database and PASCAL VOC 2007 benchmark show the effectivenessof line segment feature, and significant accuracy improvement by using fine level imageblocks for LBP. Moreover, combining LBP from different image block levels can furtherboost its performance, and outperform the state-of-the-art SIFT. Both descriptors arealso proven to provide complementary information to the SIFT

Visual Object Recognition using Local Binary Patterns and Segment-based Feature

International audienceVisual object recognition is one of the most challenging problems in computer vision, due to both inter-class and intra-class variations. The local appearance-based features, especially SIFT, have gained a big success in such a task because of their great discriminative power. In this paper, we propose to adopt two different kinds of feature to characterize different aspects of object. One is the Local Binary Pattern (LBP) operator which catches texture structure, while the other one is segment-based feature which catches geometric information. The experimental results on PASCAL VOC benchmark show that the LBP operator can provide complementary information to SIFT, and segment-based feature is mainly effective to rigid objects, which means its usefulness is class-specific. We evaluated our features and approach by participating in PASCAL VOC Challenge 2009 for the very first attempt, and achieved decent results

Visual object recognition using multi-scale local binary patterns and line segment feature

International audienceVisual content description is a key issue for machine-based visual objectrecognition, which is one of the most challenging problems in computer vision, dueto intra-class variations and inter-class similarities. A good visual descriptor should bediscriminative enough and computationally efficient while displaying some propertiesof robustness to variations. The recent literature has featured local appearance-basedfeatures, e.g. SIFT, as the main trend because of their great discriminative power. Inthis paper, we propose to adopt two different kinds of feature to characterize differentaspects of object appearance. The first is multi-scale local binary pattern (LBP) operator,which is extracted from coarse-to-fine image blocks to well describe texture structureswhile keeping its computational efficiency. The second is line segment feature, which isbased on Gestalt-inspired region segmentation and fast Hough transform, and aims atcapturing accurate geometric information of visual objects. The experimental results onthe SIMPLIcity database and PASCAL VOC 2007 benchmark show the effectivenessof line segment feature, and significant accuracy improvement by using fine level imageblocks for LBP. Moreover, combining LBP from different image block levels can furtherboost its performance, and outperform the state-of-the-art SIFT. Both descriptors arealso proven to provide complementary information to the SIFT

Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation

Reversing HIV-1 latency promotes the killing of infected cells and is essential for cure strategies. However, current latency-reversing agents (LRAs) are not entirely effective and safe in activating latent viruses in patients. In this study, we investigated whether Scopoletin (6-Methoxy-7-hydroxycoumarin), an important coumarin phytoalexin found in plants with multiple pharmacological activities, can reactivate HIV-1 latency and elucidated its underlying mechanism. Using the Jurkat T cell model of HIV-1 latency, we found that Scopoletin can reactivate latent HIV-1 replication with a similar potency to Prostratin and did so in a dose- and time-dependent manner. Moreover, we provide evidence indicating that Scopoletin-induced HIV-1 reactivation involves the nuclear factor kappa B (NF-κB) signaling pathway. Importantly, Scopoletin did not have a stimulatory effect on T lymphocyte receptors or HIV-1 receptors. In conclusion, our study suggests that Scopoletin has the potential to reactivate latent HIV-1 without causing global T-cell activation, making it a promising treatment option for anti-HIV-1 latency strategies