Analysis of two susceptibility SNPs in HLA region and evidence of interaction between rs6457617 in <Emphasis Type="BoldItalic">HLA-DQB1</Emphasis> and <Emphasis Type="BoldItalic">HLA-DRB1</Emphasis>*04 locus on Tunisian rheumatoid arthritis

Previous genomewide association studies (GWAS) and meta-analyses have enumerated several genes/loci in major histocompatibility complex region, which are consistently associated with rheumatoid arthritis (RA) in different ethnic populations. Given the genetic heterogeneity of the disease, it is necessary to replicate these susceptibility loci in other populations. In this case, we investigate the analysis of two SNPs, rs13192471 and rs6457617, from the human leukocyte antigen (HLA) region with the risk of RA in Tunisian population. These SNPs were previously identified to have a strong RA association signal in several GWAS studies. A case–control sample composed of 142 RA patients and 123 healthy controls was analysed. Genotyping of rs13192471 and rs6457617 was carried out using real-time PCR methods by TaqMan allelic discrimination assay. A trend of significant association was found in rs6457617 TT genotype with susceptibility to RA (\(P = 0.04\), \(p_{c} = 0.08\), \(\hbox {OR} = 1.73\)). Moreover, using multivariable analysis, the combination of rs6457617*TT–HLA-DRB1*\(04^{+}\) increased risk of RA (\(\hbox {OR} = 2.38\)), which suggest a gene–gene interaction event between rs6457617 located within the HLA-DQB1 and HLA-DRB1. Additionally, haplotypic analysis highlighted a significant association of rs6457617*T–HLA-DRB1*\(04^{+}\) haplotype with susceptibility to RA (\(P = 0.018\), \(p_{c} = 0.036\), \(\hbox {OR} = 1.72\)). An evidence of association was shown subsequently in \(\hbox {antiCCP}^{+}\) subgroup with rs6457617 both in T allele and TT genotype (\(P = 0.01\), \(p_{c} = 0.03\), \(\hbox {OR} = 1.66\) and \(P = 0.008\), \(p_{c} = 0.024\), \(\hbox {OR} = 1.28\), respectively). However, no association was shown for rs13192471 polymorphism with susceptibility and severity to RA. This study suggests the involvement of rs6457617 locus as risk variant for susceptibility/severity to RA in Tunisian population. Secondly, it highlights the gene–gene interaction between HLA-DQB1 and HLA-DRB1.     

Expression of sarcolectin in the human pituitary gland and amniotic fluid

Sarcolectin (SCL) is a 55 kDa protein cross-reacting with a cytokeratin 7 monomer found in placental blood, sarcomas and various tissues. It blocks the synthesis of interferon-dependent secondary proteins, induces cell DNA activation and sensitizes cells to viral infection. SCL is a potent promoter of tissue growth. In the present report, we demonstrate that SCL is expressed in the human pituitary gland at the mRNA and protein levels. We show also its presence in human amniotic fluid in high titres while interferon titres is weak. These results allow to postulate a potential role of SCL as a growth factor participating in human foetal development.     

A G-C-Rich Palindromic Structural Motif and a Stretch of Single-Stranded Purines Are Required for Optimal Packaging of Mason-Pfizer Monkey Virus (MPMV) Genomic RNA

During retroviral RNA packaging, two copies of genomic RNA are preferentially packaged into the budding virus particles whereas the spliced viral RNAs and the cellular RNAs are excluded during this process. Specificity towards retroviral RNA packaging is dependent upon sequences at the 5′ end of the viral genome, which at times extend into Gag sequences. It has earlier been suggested that the Mason-Pfizer monkey virus (MPMV) contains packaging sequences within the 5′ untranslated region (UTR) and Gag. These studies have also suggested that the packaging determinants of MPMV that lie in the UTR are bipartite and are divided into two regions both upstream and downstream of the major splice donor. However, the precise boundaries of these discontinuous regions within the UTR and the role of the intervening sequences between these dipartite sequences towards MPMV packaging have not been investigated. Employing a combination of genetic and structural prediction analyses, we have shown that region “A”, immediately downstream of the primer binding site, is composed of 50 nt, whereas region “B” is composed of the last 23 nt of UTR, and the intervening 55 nt between these two discontinuous regions do not contribute towards MPMV RNA packaging. In addition, we have identified a 14-nt G-C-rich palindromic sequence (with 100% autocomplementarity) within region A that has been predicted to fold into a structural motif and is essential for optimal MPMV RNA packaging. Furthermore, we have also identified a stretch of single-stranded purines (ssPurines) within the UTR and 8 nt of these ssPurines are duplicated in region B. The native ssPurines or its repeat in region B when predicted to refold as ssPurines has been shown to be essential for RNA packaging, possibly functioning as a potential nucleocapsid binding site. Findings from this study should enhance our understanding of the steps involved in MPMV replication including RNA encapsidation process.     

Binding of Subdomains 1/2 of PfEMP1-DBL1α to Heparan Sulfate or Heparin Mediates Plasmodium falciparum Rosetting

The capacity of Plasmodium falciparum parasitized erythrocytes (pRBC) to adhere to the endothelial lining in the microvasculature and to red blood cells (RBC) is associated with the virulence of the parasite, the pathogenesis and development of severe malaria. Rosetting, the binding of uninfected RBC to pRBC, is frequently observed in individuals with severe malaria and is mediated by the N-terminal NTS-DBL1α domain of the adhesin Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) expressed at the surface of the pRBC. Heparan sulfate has been suggested to be an important receptor for the NTS-DBL1α variant IT4_var60 expressed by the parasite FCR3S1.2. Here, we have determined the binding site of NTS-DBL1α (IT4_var60) to the RBC and heparin using a set of recombinant, mutated proteins expressed in and purified from E. coli. All the variants were studied for their ability to bind to RBC, their capacities to disrupt FCR3S1.2 rosettes, their affinities for heparin and their binding to rosette-disruptive mAbs. Our results suggest that NTS-DBL1α mediates binding to RBC through a limited number of basic amino acid residues localized on the surface of subdomains 1 (SD1) and 2 (SD2). The SD2-binding site is localized in close proximity to one of two previously identified binding sites in the rosetting PfEMP1 of the parasite PaloAlto-varO. The binding site in SD2 of NTS-DBL1α could represent a template for the development of anti-rosetting drugs.     

Aqueous date fruit extract protects against lipid peroxidation and improves antioxidant status in the liver of rats subchronically exposed to trichloroacetic acid

Trichloroacetic acid (TCA) is a prominent by-product of the chlorination of drinking water. It induces cell damage by producing free radicals and reactive oxygen species. The present study was carried out to evaluate the potential hepatoprotective role of the aqueous date extract (ADE) against TCA-induced liver injury. Forty-eight male Wistar rats were randomly divided into six groups of eight: group I served as the control; group II was given ADE by gavage; groups III and IV received TCA as drinking water at 0.5 and 2 g/L, respectively; and groups V and VI were treated with ADE by gavage and then received TCA at 0.5 and 2 g/L, respectively, as drinking water. The experiment was performed for 2 months. The hepatotoxicity of TCA administration was revealed by an increase in the levels of hepatic marker enzymes (transaminases, gamma-glutamyl transferase, and lactate dehydrogenase) and conjugated bilirubin and a decrease in albumin level. The TCA administration induced also significant elevation of the malondialdehyde (MDA) level and the antioxidant activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) paralleled with a significant decline in catalase (CAT) activity. These biochemical alterations were accompanied by histological changes marked by the appearance of vacuolization, necrosis, congestion, inflammation, and enlargement of sinusoids in the liver section. Treatment with date palm fruit extract restored the liver damage induced by TCA, as demonstrated by inhibition of hepatic lipid peroxidation; amelioration of SOD, GPx, and CAT activities; and improvement of histopathology changes. These results suggest that ADE has a protective effect over TCA-induced oxidative damage in rat liver.     

Fuzzy ART-based place recognition for visual loop closure detection

The automatic place recognition problem is one of the key challenges in SLAM approaches for loop closure detection. Most of the appearance-based solutions to this problem share the idea of image feature extraction, memorization, and matching search. The weakness of these solutions is the storage and computational costs which increase drastically with the environment size. In this regard, the major constraints to overcome are the required visual information storage and the complexity of similarity computation. In this paper, a novel formulation is proposed that allows the computation time reduction while no visual information are stored and matched explicitly. The proposed solution relies on the incremental building of a bio-inspired visual memory using a Fuzzy ART network. This network considers the properties discovered in primate brain. The performance evaluation of the proposed method has been conducted using two datasets representing different large scale outdoor environments. The method has been compared with RatSLAM and FAB-MAP approaches and has demonstrated a decreased time and storage costs with broadly comparable precision recall performance.     

Functional inhibition by cyclosporin A of the lymphocyte receptor for the AIDS virus (HIV)

The Human Immunodeficiency Virus (HIV) displays a selective tropism for cells expressing the CD4 molecule which, by itself, represents at least part of the specific receptor for this virus. However, modification of the activation state of each individual cell seems critical not only for virus replication but also for its binding and subsequent penetration into its target. We demonstrate here that Cyclosporin-A (CSA), a drug which inhibits IL-2 dependent T-lymphocyte proliferation and differentiation and which is known for its immunosuppressive activity, can prevent subsequent virus binding to cells otherwise susceptible to HIV. Normal T-lymphocytes were preincubated in vitro with CSA at concentrations that were in the same range than those reached in the serum of treated patients. This resulted in the complete disappearance of HIV receptors (HIV-R), as assessed by the direct measure of specific binding of fluoresceinated HIV (HIV-FITC), and in the subsequent inhibition of HIV replication in cultured cells. Moreover CSA pretreatment of IL-2 independent transformed cells derived from the CEM line, before their infection, strongly inhibited HIV adsorption as well as further virus replication. These results provide a new experimental basis for the potential application of CSA in the treatment of HIV-related diseases.     

A Comprehensive Characterisation of Rosemary tea Obtained from Rosmarinus officinalis L. Collected in a sub‐Humid Area of Tunisia

Introduction

Rosemary (Rosmarinus officinalis L.) is an aromatic plant common in Tunisia and it is widely consumed as a tea in traditional cuisine and in folk medicine to treat various illnesses. Currently, most research efforts have been focused on rosemary essential oil, alcoholic and aqueous extracts, however, little is reported on rosemary infusion composition.

Objective

To investigate compounds present in rosemary tea obtained from Rosmarinus officinalis L. collected in a sub‐humid area of Tunisia in order to assess whether the traditional rosemary tea preparation method could be considered as a reference method for rosemary's compounds extraction.

Methodology

Qualitative characterisation of Rosmarinus officinalis tea obtained after rosemary infusion in boiled water was determined by high performance liquid chromatography coupled with electrospray ionisation quadrupole time‐of‐flight mass spectrometry (HPLC‐ESI‐QTOF‐MS). Quantitative analysis relies on high performance liquid chromatography with diode array detector (HPLC‐DAD).

Results

Forty‐nine compounds belonging to six families, namely flavonoids, phenolic acids, phenolic terpenes, jasmonate, phenolic glycosides, and lignans were identified. To the best of the authors' knowledge eucommin A is characterised for the first time in rosemary. Rosmarinic acid (158.13 μg/g dried rosemary) was the main compound followed then by feruloylnepitrin (100.87 μg/g) and luteolin‐3′‐O‐(2″‐O‐acetyl)‐β‐d ‐glucuronide (44.04 μg/g). Among quantified compounds, luteolin‐7‐O‐rutinoside was the compound with the lowest concentration.

Conclusion

The infusion method allows several polyphenols present in rosemary tea to be extracted, therefore it could be a reference method for rosemary's compounds extraction. Moreover, traditional Tunisian Rosmarinus officinalis tea consumption is of interest for its rich phenolic content. Copyright © 2017 John Wiley & Sons, Ltd.     

Crystal structure of the major Malassezia sympodialis allergen Mala s 1 reveals a beta-propeller fold: a novel fold among allergens

Atopic eczema (AE) is a chronic inflammatory disease in which genetic predisposition and environmental factors such as microorganisms contribute to the symptoms. The yeast Malassezia Sympodialis, part of the normal human cutaneous flora, can act as an allergen eliciting specific IgE and T-cell reactivity in patients with AE. The major M. sympodialis allergen Mala s 1 is localized mainly in the yeast cell wall and exposed on the cell surface. Interestingly, Mala s 1 does not exhibit any significant sequence homology to known proteins. Here we present the crystal structure of Mala s 1 determined by single-wavelength anomalous dispersion techniques using selenomethionine-substituted Mala s 1. Mala s 1 folds into a 6-fold beta-propeller, a novel fold among allergens. The putative active site of Mala s 1 overlaps structurally to putative active sites in potential homologues, Q4P4P8 and Tri 14, from the plant parasites Ustilago maydis and Gibberella zeae, respectively. This resemblance suggests that Mala s 1 and the parasite proteins may have similar functions. In addition, we show that Mala s 1 binds to the phosphoinositides (PI) PI(3)P, PI(4)P, and PI(5)P, lipids possibly playing a role in the localization of Mala s 1 to the cell surface. The crystal structure of Mala s 1 will provide insights into the role of this major allergen in the host-microbe interactions and induction of an allergic response in AE.