The COL5A3 and MMP9 genes interact in eczema susceptibility.

BACKGROUND: Genetic studies of eczema have identified many genes, which explain only 14% of the heritability. Missing heritability may be partly due to ignored gene-gene (G-G) interactions. OBJECTIVE: Our aim was to detect new interacting genes involved in eczema. METHODS: The search for G-G interaction in eczema was conducted using a two-step approach, which included as a first step, a biological selection of genes, which are involved either in the skin or epidermis development or in the collagen metabolism, and as a second step, an interaction analysis of the selected genes. Analyses were carried out at both SNP and gene levels in three asthma-ascertained family samples: the discovery dataset of 388 EGEA (Epidemiological study on the Genetics and Environment of Asthma) families and the two replication datasets of 253 SLSJ (Saguenay-Lac-Saint-Jean) families and 207 MRCA (Medical Research Council) families. RESULTS: One pair of SNPs, rs2287807 in COL5A3 and rs17576 in MMP9, that were detected in EGEA at P ≤ 10-5 showed significant interaction by meta-analysis of EGEA, SLSJ and MRCA samples (P = 1.1 × 10-8 under the significant threshold of 10-7 ). Gene-based analysis confirmed strong interaction between COL5A3 and MMP9 (P = 4 × 10-8 under the significant threshold of 4 × 10-6 ) by meta-analysis of the three datasets. When stratifying the data on asthma, this interaction remained in both groups of asthmatic and non-asthmatic subjects. CONCLUSION: This study identified significant interaction between two new genes, COL5A3 and MMP9, which may be accounted for by a degradation of COL5A3 by MMP9 influencing eczema susceptibility. Further confirmation of this interaction as well as functional studies is needed to better understand the role of these genes in eczema.

Rosenbluth Separation of the π

We report the first longitudinal-transverse separation of the deeply virtual exclusive π^{0} electroproduction cross section off the neutron and coherent deuteron. The corresponding four structure functions dσ_{L}/dt, dσ_{T}/dt, dσ_{LT}/dt, and dσ_{TT}/dt are extracted as a function of the momentum transfer to the recoil system at Q^{2}=1.75 GeV^{2} and x_{B}=0.36. The ed→edπ^{0} cross sections are found compatible with the small values expected from theoretical models. The en→enπ^{0} cross sections show a dominance from the response to transversely polarized photons, and are in good agreement with calculations based on the transversity generalized parton distributions of the nucleon. By combining these results with previous measurements of π^{0} electroproduction off the proton, we present a flavor decomposition of the u and d quark contributions to the cross section.

Rosenbluth Separation of the π

We present deeply virtual π^{0} electroproduction cross-section measurements at x_{B}=0.36 and three different Q^{2} values ranging from 1.5 to 2 GeV^{2}, obtained from Jefferson Lab Hall A experiment E07-007. The Rosenbluth technique is used to separate the longitudinal and transverse responses. Results demonstrate that the cross section is dominated by its transverse component and, thus, is far from the asymptotic limit predicted by perturbative quantum chromodynamics. Nonetheless, an indication of a nonzero longitudinal contribution is provided by the measured interference term σ_{LT}. Results are compared with several models based on the leading-twist approach of generalized parton distributions (GPDs). In particular, a fair agreement is obtained with models in which the scattering amplitude includes convolution terms of chiral-odd (transversity) GPDs of the nucleon with the twist-3 pion distribution amplitude. This experiment, together with previous extensive unseparated measurements, provides strong support to the exciting idea that transversity GPDs can be accessed via neutral pion electroproduction in the high-Q^{2} regime.

A common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults.

BACKGROUND: Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. OBJECTIVE: We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. METHODS: We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N = 610 adults) and the Hutterites (N = 601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N = 450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations, and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N = 8858) consortium. RESULTS: We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P = 1.6 × 10(-7) ) in the combined discovery and replication adult data sets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P = 8.9 × 10(-7) ) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. CONCLUSIONS AND CLINICAL RELEVANCE: This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults.

Which knee and probe position determines the final diagnosis of knee inflammation by ultrasound? Results from a European multicenter study.

PURPOSE: To investigate which knee and probe position best identifies knee inflammation and to determine a cut-off level for abnormal synovial effusion. MATERIALS AND METHODS: 18 experienced sonographers (all rheumatologists) performed ultrasound examinations of the knee joint in patients with knee symptoms and in healthy controls. Each sonographer performed longitudinal suprapatellar ultrasound scans using 9 different configurations at each knee: Midline, parapatallar lateral and parapatellar medial from midline in neutral position (0°) with and without quadriceps muscle contraction and in 30° flexion of the knee. The presence of synovial effusion (SE), the effusion measured in millimeters and the presence of synovial hypertrophy (SH) was noted. RESULTS: A total of 298 knees of 149 subjects (129 patients and 20 controls) were examined. The detection of SH is more sensitive and specific than the detection of SE, independently of the knee and probe position, for the final diagnosis of abnormality. The detection of both synovial hypertrophy and effusion in the knee in neutral position (0°) with quadriceps contraction and with the probe in the midline position, are the best independent predictors for knee abnormalities. Knee effusion > 3.2 mm measured with the probe in the lateral aspect of the knee is the best diagnostic characteristics for predicting pathological SE. CONCLUSION: The best combination for detecting SH and SE is obtained by placing the probe in the midline position with the knee in 0° with quadriceps contraction. A cut-off value for pathological effusion may be obtained in the lateral aspect of the knee.

Network-assisted analysis of GWAS data identifies a functionally-relevant gene module for childhood-onset asthma.

The number of genetic factors associated with asthma remains limited. To identify new genes with an undetected individual effect but collectively influencing asthma risk, we conducted a network-assisted analysis that integrates outcomes of genome-wide association studies (GWAS) and protein-protein interaction networks. We used two GWAS datasets, each consisting of the results of a meta-analysis of nine childhood-onset asthma GWASs (5,924 and 6,043 subjects, respectively). We developed a novel method to compute gene-level P-values (fastCGP), and proposed a parallel dense-module search and cross-selection strategy to identify an asthma-associated gene module. We identified a module of 91 genes with a significant joint effect on childhood-onset asthma (P < 10-5). This module contained a core subnetwork including genes at known asthma loci and five peripheral subnetworks including relevant candidates. Notably, the core genes were connected to APP (encoding amyloid beta precursor protein), a major player in Alzheimer's disease that is known to have immune and inflammatory components. Functional analysis of the module genes revealed four gene clusters involved in innate and adaptive immunity, chemotaxis, cell-adhesion and transcription regulation, which are biologically meaningful processes that may underlie asthma risk. Our findings provide important clues for future research into asthma aetiology.

A glimpse of gluons through deeply virtual compton scattering on the proton.

The internal structure of nucleons (protons and neutrons) remains one of the greatest outstanding problems in modern nuclear physics. By scattering high-energy electrons off a proton we are able to resolve its fundamental constituents and probe their momenta and positions. Here we investigate the dynamics of quarks and gluons inside nucleons using deeply virtual Compton scattering (DVCS)-a highly virtual photon scatters off the proton, which subsequently radiates a photon. DVCS interferes with the Bethe-Heitler (BH) process, where the photon is emitted by the electron rather than the proton. We report herein the full determination of the BH-DVCS interference by exploiting the distinct energy dependences of the DVCS and BH amplitudes. In the regime where the scattering is expected to occur off a single quark, measurements show an intriguing sensitivity to gluons, the carriers of the strong interaction.

In-depth analysis of chloride treatments for thin-film CdTe solar cells.

CdTe thin-film solar cells are now the main industrially established alternative to silicon-based photovoltaics. These cells remain reliant on the so-called chloride activation step in order to achieve high conversion efficiencies. Here, by comparison of effective and ineffective chloride treatments, we show the main role of the chloride process to be the modification of grain boundaries through chlorine accumulation, which leads an increase in the carrier lifetime. It is also demonstrated that while improvements in fill factor and short circuit current may be achieved through use of the ineffective chlorides, or indeed simple air annealing, voltage improvement is linked directly to chlorine incorporation at the grain boundaries. This suggests that focus on improved or more controlled grain boundary treatments may provide a route to achieving higher cell voltages and thus efficiencies.

Matrix metalloproteinase inhibition by green tea catechins.

We have investigated the effects of different biologically active components from natural products, including green tea polyphenols (GTP), resveratrol, genistein and organosulfur compounds from garlic, on matrix metalloproteinase (MMP)-2, MMP-9 and MMP-12 activities. GTP caused the strongest inhibition of the three enzymes, as measured by fluorescence assays using gelatin or elastin as substrates. The inhibition of MMP-2 and MMP-9 caused by GTP was confirmed by gelatin zymography and was observed for MMPs associated with both various rat tissues and human brain tumors (glioblastoma and pituitary tumors). The activities of MMPs were also measured in the presence of various catechins isolated from green tea including (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate(ECG), (-)-epigallocatechin (EGC), (-)-epicatechin (EC) and (+)-catechin (C). The most potent inhibitors of these activities, as measured by fluorescence and by gelatin or casein zymography, were EGCG and ECG. GTP and the different catechins had no effect on pancreatic elastase, suggesting that the effects of these molecules on MMP activities are specific. Furthermore, in vitro activation of proMMP-2 secreted from the glioblastomas cell line U-87 by the lectin concanavalin A was completely inhibited by GTP and specifically by EGCG. These results indicate that catechins from green tea inhibit MMP activities and proMMP-2 activation.

Dexamethasone modulation of multidrug transporters in normal tissues.

The expression of P-glycoprotein (P-gp) and canalicular multispecific organic anion transporter (cMOAT or Mrp2) was evaluated by Western blotting analysis of rat tissues isolated following daily administration (1 mg kg(-1) day(-1)) of dexamethasone over 4 days. Dexamethasone rapidly increased P-gp expression more than 4.5- and 2-fold in liver and lung, respectively, while it was decreased 40% in kidney. cMOAT expression was increased 2-fold in liver and kidney following dexamethasone treatment. The levels of both proteins returned to control values by 6 days after the conclusion of dexamethasone administration. These results indicate that dexamethasone can modulate P-gp and cMOAT expression in specific rat tissues and may have significant relevance for patients treated with dexamethasone as a single agent or in combination therapy with other drugs.

Sero-epidemiological survey for alveolar echinococcosis (by Em2-ELISA) of blood donors in an endemic area of Switzerland.

Sera from 17,166 blood donors living in 10 cantons of northern Switzerland in an area endemic for Echinococcus multilocularis were investigated by serological survey for alveolar echinococcosis (AE). A highly species-specific antigen (Em2) and a commonly used E. granulosus hydatid fluid antigen (EgHF) were compared for their suitability in seroepidemiology. EgHF showed a degree of nonspecificity which did not allow direct detection of AE cases. Antibody reaction with Em2 resulted in the detection of 2 asymptomatic clinical cases of AE (seroprevalence 0.01%) within this population of blood donors. A further 4 persons were positive in Em2-ELISA. These 4 persons had negative imaging studies and will be followed serologically and clinically.

[Immunologic relations between cattle and ticks, specifically between cattle and Boophilus microplus]. / Relations immunologiques entre bovins et tiques, plus particulièrement entre bovins et Boophilus microplus

In the present investigation, it has been demonstrated that cattle become resistant to ticks after several heavy infestations, particularly with B. microplus. During development of the infestations, antibodies against salivary glands of B. microplus were detected using 2 techniques: indirect immunofluorescence and immunoelectrophoresis. There is a positive causal relationship between antibody titer and resistance development. Two precipitating systems against B. microplus in infested cattle and 7 systems in immunized rabbits were studied. The systems 1 and 2 are similar in cattle and rabbits, but system 2 does not show any specificity, as it has been detected in cattle completely lacking tick infestations. Two one-day calves were treated with the antigen of B. microplus by injection of salivary glands and repeated infestations with a small number of larvae. They developed a pronounced resistance to the usual subsequent infestations by the ticks of the same species. Specific antibodies were found before the first usual infestation. This suggests that they might be responsible for resistance.

[Contribution to the knowledge of Swiss piroplasmas]. / Contribution á la connaissance des piroplasmes de Suisse

The authors identify 3 species of Babesia, which parasitize cattle in Switzerland (Babesia major, B. divergens and B. hovis). They also confirm the presence of B. canis in a dog in the proximity of Geneva. Finally, for the first time in Switzerland, they point out the presence of non-identified Babesia in various rodents (Apodemus sylvaticus, A. flavicollis and Clethrionomys glareolus).

[Immune response of rabbit to repeated infestations by Ornithodoros moubata Murray females: its influence on the biology of tick (author's transl)]. / Réponse immunologique du lapin aux infestations répétées de femelles d'Ornithodoros moubata Murray: son influence sur la biologie des tiques.

Antibodies against salivary gland tissues of the argasid tick, Ornithodoros moubata, were detected by indirect immunofluorescence in rabbits repeatedly fed on by ticks. This immune response appears to have little adverse affects on the biology of the tick; blood intake was found to be sometimes smaller and the feeding period somewhat longer. Attachment to the host and oviposition were not adversely affected. There exists a linear relationship between a) the weight of unfed and engorged females, and b) the weight of engorged females and the number of deposited eggs.

Modulation of erythrocyte Na transport pathway(s) by excess Na intake.

Different Na transport pathways were studied in the erythrocytes of 10 normotensive subjects who received 240 meq/day of Na in excess of their usual diet. In most of these subjects the maximal rate (Vmax) of the Na,K pump and the Na,K-cotransport system was markedly decreased on the first day of the diet. In some of these subjects, excess Na intake induced an increase in the apparent affinity for internal Na for the Na,K pump and the Na,K-cotransport system. The decrease in the Na,K pump fluxes was not concomitant to that of the co-transport system and not accompanied with an increase in blood pressure or cation concentration in the plasma. Interestingly, the apparent affinity for internal Li of the Li-Na exchange was markedly increased without alteration of the Vmax. The passive permeability for Na and the cellular Na content were not altered by excess Na intake. Ouabain and bumetanide at low concentrations respectively induced an increase in the apparent affinity for internal Na of the Na,K pump and the Na,K- cotransport system. These results are similar to those observed after excess Na intake. These later agree with the hypothesis that Na homeostasis regulates some endogenous factors with ouabain-like and furosemide-like properties that might contribute to the regulation of cellular Na handling.

Vector competence of Ixodes scapularis and Ixodes ricinus (Acari: Ixodidae) for three genospecies of Borrelia burgdorferi.

The vector competence of 2 tick species, Ixodes ricinus (L.) and Ixodes scapularis Say, was determined and compared for 3 genospecies of Borrelia burgdorferi. The 3 genospecies of B. burgdorferi used in the following experiments were Borrelia burgdorferi sensu stricto (B-31 and B-31.D1 clone), Borrelia afzelii (strain Pgau. C3), and Borrelia garinii (strain VS286 and VSBP). Spirochetes from all 5 strains were inoculated intradermally into outbred mice; larval ticks of both species were subsequently fed on those mice and replete larvae were assayed for infection by culture in BSK-H media every 7 d for 4 wk. Infection frequencies in I. scapularis exposed to the 5 strains were as follows: B-31 (90%), B-31.D1 (83%), Pgau.C3 (87%), VS286 (10%), and VSBP (5%). The comparable infection frequencies for I. ricinus were B-31 (3%), B-31.D1 (3%), Pgau.C3 (90%), VS286 (5%), and VSBP (3%). Resultant nymphal I. scapularis successfully transmitted B-31, B-31,D1, Pgau.C3, and VS286 to outbred mice. I. ricinus nymphs transmitted Pgau.C3 and VS286. Both species failed to transmit strain VSBP.

Effects of human recombinant interleukin-2 on resistance, and on the humoral and cellular response of rabbits infested with adult Ixodes ricinus ticks.

Rabbits were treated with subcutaneous injections of ten doses of 5 x 10(3) units of human recombinant interleukin-2 (IL-2) during a first infestation with five adult pairs Ixodes ricinus per rabbit, while untreated controls were infested by either five (direct control) or 25 pairs (resistant control) per rabbit. During the second infestation with 25 pairs per rabbit in each group, rabbits treated with IL-2 became more resistant than the rabbits in the two untreated control groups. Stronger resistance was manifested by lower engorgement and egg laying weights, and by smaller numbers of normally fed or ovipositioning ticks. IL-2 treatment had no significant effects on the rabbit anti-tick antibody production and the lymphocyte proliferation to a salivary gland extract (SGE). By contrast, the highest cutaneous responses to SGE were observed in the IL-2 treated group. IL-2 may increase rabbit cell-mediated immunity, and stimulate an increase in the production of memory cells during the induction phase of the immune response (first infestation), allowing the development of a strong resistance in lightly infested rabbits.

Piroplasms of domestic animals in the Macedonia region of Greece. 2. Piroplasms of cattle.

A study was carried out on piroplasms of cattle in the Macedonia region of Greece. During 1984-1986, 602 serum samples were collected from cattle in 33 localities. Blood smears were also prepared from 50 of the animals in 13 localities. The indirect fluorescent antibody (IFA) test revealed that 41.4% of cattle sera were positive to Theileria orientalis, 2.0% to Theileria annulata, 21.6% to Babesia bovis, 15.2% to Babesia bigemina, 5.1% to Babesia major and 2.7% to Babesia divergens. Some of the positive titres were probably due to cross reactions. T. orientalis was widely distributed. T. annulata was limited to a small number of foci. B. bigemina and B. bovis, often present together, were widespread, whereas B. major was only present in a small number of localities. No convincing evidence of B. divergens infection was found. By examination of Giemsa stained blood smears T. orientalis, T. annulata and a Babesia sp. were detected.

Piroplasms of domestic animals in the Macedonia region of Greece. 3. Piroplasms of small ruminants.

A study was carried out on piroplasms of small ruminants in the Macedonia region of Greece. During 1984-1985, 721 serum samples were collected from sheep in 49 localities and 487 from goats in 43 localities. Blood smears were also prepared from 26 sheep and eight goats in 16 localities. The prevalence of positive IFA titres for sheep and goat sera, respectively, was: 24.6% and 0.6% for Theileria ovis, 52.1% and 36.4% for Babesia ovis, 10.5% and 4.2% for Babesia motasi, 12.6% and 6.6% for Babesia crassa. Many of the positive reactions, specially for the large Babesia species, B. motasi and B. crassa, probably resulted from cross-reactions and the presence of these two species is doubtful. Antibodies against B. ovis were found in animals from more than 90% of the localities. T. ovis was also common, but it was confined essentially to sheep. The examination of Giemsa stained blood smears revealed the presence of T. ovis and B. ovis in sheep, and Anaplasma ovis in a goat.

Immunity of dogs against Babesia canis, its vector tick Dermacentor reticulatus, and Ixodes ricinus in endemic area.

Previous epidemiological studies allowed us to accurately define endemic areas of canine babesiosis and tick distribution in southeastern France (Martinod, 1983). Using a micro-ELISA test 100 dogs sera were tested with 3 antigens: Babesia canis, Dermacentor reticulatus and Ixodes ricinus. Antibodies against B. canis and its vector D. reticulatus were detected in an endemic area, sometimes with high levels (optical density 1.38 and 0.80 respectively). A correlation factor and regression lines were found between ELISA activity of B. canis and vector tick antigens, even for dogs which never showed any babesiosis symptoms. These results were compared with those of an area without any babesiosis. Furthermore I. ricinus antigens detected ELISA activity in sera of dogs; some cross reactions were observed between I. ricinus and D. reticulatus antigen.