IQ-motif peptides as novel anti-microbial agents

The IQ-motif is an amphipathic, often positively charged, a-helical, calmodulin binding sequence found in a number of eukaryote signalling, transport and cytoskeletal proteins. They share common biophysical characteristics with established, cationic a-helical antimicrobial peptides, such as the human cathelicidin LL-37. Therefore, we tested eight peptides encoding the sequences of IQ-motifs derived from the human cytoskeletal scaffolding proteins IQGAP2 and IQGAP3. Some of these peptides were able to inhibit the growth of Escherichia coli and Staphylococcus aureus with minimal inhibitory concentrations (MIC) comparable to LL-37. In addition some IQ-motifs had activity against the fungus Candida albicans. This antimicrobial activity is combined with low haemolytic activity (comparable to, or lower than, that of LL-37). Those IQ-motifs with anti-microbial activity tended to be able to bind to lipopolysaccharide. Some of these were also able to permeabilise the cell membranes of both Gram positive and Gram negative bacteria. These results demonstrate that IQ-motifs are viable lead sequences for the identification and optimisation of novel anti-microbial peptides. Thus, further investigation of the anti-microbial properties of this diverse group of sequences is merited.

Local materials for building houses: Laterite valorization in Africa

This paper presents the preliminary results of geological and geomechanical studies on the laterite stone exploited at Dano quarry in Burkina Faso. The field work described the geological structure of quarry sites and their environment to determine the rocks alteration and the links between the bedrock and lateritic material. Physic-mechanical properties have been studied for assessing the potentiality of this material for lightweight housing, to be completed with thermal and environmental considerations. Some social and economic evaluations are in progress in order to foster its utilization under local conditions. © (2014) Trans Tech Publications, Switzerland.

Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection

Background: Differentiation between septic and aseptic loosening of joint replacements is essential for successful revision surgery, but reliable markers for the diagnosis of low-grade infection are lacking. The present study was performed to assess intra-articular and systemic levels of antimicrobial peptides and proinflammatory cytokines as diagnostic markers for periprosthetic joint infection. Methods: Fifteen consecutive patients with staphylococcal periprosthetic joint infections and twenty control patients with aseptic loosening of total hip and knee replacements were included in this prospective, single-center, controlled clinical trial. Expression of the antimicrobial peptides human β-defensin-2 (HBD-2), human β-defensin-3 (HBD-3), and cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in serum and joint aspirates with use of cytometric bead arrays. C-reactive protein in serum, microbiology, and histopathology of periprosthetic tissue served as the “gold standard” for the diagnosis of infection. Results: The antimicrobial peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from patients with periprosthetic joint infection compared with patients with aseptic loosening, and the area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 0.745 and 0.875, respectively. Additionally, significant local increases in the proinflammatory cytokines interleukin (IL)-1β, IL-4, IL-6, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were observed to be associated with infection. Logistic regression analysis indicated that the combination of an antimicrobial peptide with another synovial fluid biomarker improved diagnostic accuracy; the AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3 and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial peptides and cytokines in serum that showed a significant systemic increase in association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC value of <0.75). Conclusions: The present study showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection, and analysis of the levels in synovial fluid was more accurate than analysis of serum.

Transatlantic distribution of the Alaskan White River Ash

Volcanic ash layers preserved within the geologic record represent precise time markers that correlate disparate depositional environments and enable the investigation of synchronous and/or asynchronous behaviors in Earth system and archaeological sciences. However, it is generally assumed that only exceptionally powerful events, such as supereruptions (≥450 km3 of ejecta as dense-rock equivalent; recurrence interval of ∼105 yr), distribute ash broadly enough to have an impact on human society, or allow us to address geologic, climatic, and cultural questions on an intercontinental scale. Here we use geochemical, age, and morphological evidence to show that the Alaskan White River Ash (eastern lobe; A.D. 833–850) correlates to the “AD860B” ash (A.D. 846–848) found in Greenland and northern Europe. These occurrences represent the distribution of an ash over 7000 km, linking marine, terrestrial, and ice-core records. Our results indicate that tephra from more moderate-size eruptions, with recurrence intervals of ∼100 yr, can have substantially greater distributions than previously thought, with direct implications for volcanic dispersal studies, correlation of widely distributed proxy records, and volcanic hazard assessment.

Family Nurse Partnership: Meeting the needs of teenage mothers

Meeting the needs of young parents and their children more effectively will improve their life and long term health. This paper examines the Family Nurse Partnership as a public health initiative in supporting young women and improving the outcomes of themselves and their child(ren). It explores evidence of effectiveness, cost benefit and resource implications and discusses the role of the midwife within the context of public health initiatives and specifically to the delivery of the Family Nurse Partnership.

Tri-Band HIS Backed Spiral Antenna for Wireless LAN Applications

This study reports the performance of an Archimedean spiral antenna, which exhibits unidirectional circularly polarized radiation patterns with a peak gain >8 dBic in the lower (2.4–2.485 GHz) and upper (5.15–5.35 and 5.725–5.875 GHz) Wireless local area network frequency bands. The required backlobe suppression and impedance match are obtained by placing a multiresonant high impedance surface (HIS) in close proximity to the radiating aperture. Simulated and measured radiation patterns are shown at the center frequency of all three channels and a comparison of the key performance metrics is made with free space and metal backed antenna arrangements to demonstrate the enhancements which are attributed to the HIS reflector.

Free fatty acid receptors:structural models and elucidation of ligand binding interactions

BACKGROUND: The free fatty acid receptors (FFAs), including FFA1 (orphan name: GPR40), FFA2 (GPR43) and FFA3 (GPR41) are G protein-coupled receptors (GPCRs) involved in energy and metabolic homeostasis. Understanding the structural basis of ligand binding at FFAs is an essential step toward designing potent and selective small molecule modulators.

RESULTS: We analyse earlier homology models of FFAs in light of the newly published FFA1 crystal structure co-crystallized with TAK-875, an ago-allosteric ligand, focusing on the architecture of the extracellular binding cavity and agonist-receptor interactions. The previous low-resolution homology models of FFAs were helpful in highlighting the location of the ligand binding site and the key residues for ligand anchoring. However, homology models were not accurate in establishing the nature of all ligand-receptor contacts and the precise ligand-binding mode. From analysis of structural models and mutagenesis, it appears that the position of helices 3, 4 and 5 is crucial in ligand docking. The FFA1-based homology models of FFA2 and FFA3 were constructed and used to compare the FFA subtypes. From docking studies we propose an alternative binding mode for orthosteric agonists at FFA1 and FFA2, involving the interhelical space between helices 4 and 5. This binding mode can explain mutagenesis results for residues at positions 4.56 and 5.42. The novel FFAs structural models highlight higher aromaticity of the FFA2 binding cavity and higher hydrophilicity of the FFA3 binding cavity. The role of the residues at the second extracellular loop used in mutagenesis is reanalysed. The third positively-charged residue in the binding cavity of FFAs, located in helix 2, is identified and predicted to coordinate allosteric modulators.

CONCLUSIONS: The novel structural models of FFAs provide information on specific modes of ligand binding at FFA subtypes and new suggestions for mutagenesis and ligand modification, guiding the development of novel orthosteric and allosteric chemical probes to validate the importance of FFAs in metabolic and inflammatory conditions. Using our FFA homology modelling experience, a strategy to model a GPCR, which is phylogenetically distant from GPCRs with the available crystal structures, is discussed.

A method of measuring anterior chamber volume using the anterior segment optical coherence tomographer and specialized software.

PURPOSE: To describe and evaluate a new method for measuring anterior chamber volume (ACV). DESIGN: Observational case series. METHODS: The authors measured ACV using the anterior chamber (AC) optical coherence tomographer (OCT) and applied image-processing software developed by them. Repeatability was evaluated. The ACV was measured in patient groups with normal ACs, shallow ACs, and deep ACs. The volume difference before and after laser peripheral iridotomy (LPI) was analyzed for the shallow and deep groups. RESULTS: Coefficients of repeatability for intraoperator, interoperator, and interimage measurements were 0.406%, 0.958%, and 0.851%, respectively. The limits of agreement for intraoperator and interoperator measurement were -0.911 microl to 1.343 microl and -7.875 microl to -2.463 microl, respectively. There were significant ACV differences in normal, shallow, and deep AC eyes (P < .001) and before and after LPI in shallow AC (P < .001) and deep AC (P = .008) eyes. CONCLUSIONS: The ACV values obtained by this method were repeatable and in accord with clinical observation.

Handmade Films: Questioning and Integrating Cinematic Technology

Artigo publicado enquanto investigadora na Universidade de Aalborg, Dinamarca.

Travailler ensemble à l'école primaire qu'en pensent des acteurs de l'ÉPS du milieu scolaire et de la formation à l'enseignement?

Au Québec, les réformes du système scolaire implantées depuis 2001 au primaire appellent à modifier considérablement la tâche des personnes enseignantes. L'appel au professionnalisme collectif s'oppose à une conception plus traditionnelle du travail de l'enseignant"seul devant ses élèves". Cette dimension du travail enseignant est également présente à l'intérieur de la formation initiale à l'enseignement (Gouvernement du Québec, 200 lb). Parmi les douze compétences professionnelles, deux d'entre elles se réfèrent au travail entre les personnes impliquées dans les apprentissages des élèves. Dans le domaine de l'éducation physique et à la santé (EPS) au primaire, un certain nombre de transformations observées depuis quelques années sont susceptibles d'influencer le travail entre personnes enseignantes. En effet, plusieurs spécialistes en éducation physique et à la santé sont de plus en plus fréquemment appelés à enseigner dans un contexte de co-enseignement (team teaching). Le programme de formation de l'école québécoise (Gouvernement du Québec, 200la) invite également les spécialistes d'éducation physique et à la santé à travailler à l'intérieur des équipes-cycles. Finalement, les spécialistes de l'ÉPS se sont vus attribuer la responsabilité du volet éducation à la santé à l'école par le biais de la compétence disciplinaire Adopter un mode de vie sain et actif . Depuis ces récentes transformations, les spécialistes en ÉPS sont davantage appelés à travailler avec des acteurs du milieu scolaire qu'auparavant. L'objectif général de cette étude est de comprendre comment des acteurs oeuvrant dans le domaine de l'ÉPS au primaire voient le"travailler ensemble" comme dimension du travail enseignant et comme objet de formation. Plus précisément, les questions de recherche sont liées aux thèmes suivants : 1) le sens que les acteurs du milieu scolaire donnent au concept du"travailler ensemble"; 2) les conditions et les obstacles à la mise en place et à l'accomplissement dû"travailler ensemble"; 3) la place qu'occupe la formation au"travailler ensemble" à l'intérieur du programme de formation à l'enseignement ciblé dans cette étude. Sur le plan conceptuel, cette étude est confrontée à la polysémie des terminologies des concepts qui font référence au"travailler ensemble". Dans cette optique, nous chercherons à définir les différents concepts qui s'y rapportent. Nous présenterons un modèle conceptuel du"travailler ensemble" à partir d'autres référents traitant du même thème. Le modèle conceptuel s'opérationnalisera selon deux concepts, soit celui d'intensité et celui d'interdépendance. Cette étude emprunte une approche de recherche qualitative de type interprétative, elle est menée auprès de onze (n = 11) acteurs du milieu scolaire (personnes enseignantes associées en EPS (n = 4), directions d'école (n = 2) et auprès d'acteurs issus d'un programme de formation à l'enseignement de l'ÉPS (stagiaires en EPS (n = 3), formateurs universitaires à l'enseignement (n = 2)). Il s'agit d'un échantillon non probabiliste de type critérié (Patton, 1990). Les résultats ont été recueillis par le biais de questionnaires sociodémographiques et d'entrevues semi-dirigées. La présence d'acteurs provenant de quatre catégories différentes nous permettra d'effectuer une triangulation par les sources d'informations (Savoie-Zajc et Karsenti, 2000). Les entrevues nous révèlent que les acteurs rencontrés ont diverses occasions de travailler avec leurs collègues à l'école et que les conditions varient selon le rôle occupé par les personnes (enseignantes d'une même discipline, enseignantes d'une discipline différente ou non enseignantes). Chez les spécialistes en EPS que nous avons rencontrés, nous observons que le travail entre collègues d'une même discipline dépasse les limites de l'école. Ce contexte s'avère propice au renforcement d'une identité professionnelle commune. Les acteurs rencontrés identifient des conditions favorables et défavorables au"travailler ensemble". Celles-ci prennent diverses formes. Elles sont tantôt de nature affective, organisationnelle ou identitaire. En ce qui concerne la place occupée par la formation au"travailler ensemble" à l'intérieur du programme d'ÉPS participant, il semble que les occasions de développer cette compétence soient plus pertinentes à l'intérieur des stages qu'à l'intérieur des cours donnés à l'université. Par contre, les occasions de"travailler ensemble" en stage varient en fonction du contexte d'intervention de la personne enseignante associée. Cette situation soulève un certain nombre d'interrogations se rapportant tant à la capacité de la personne enseignante à s'adapter aux récentes transformations de l'école québécoise qu'aux programmes actuels de formation à l'enseignement pour former les futures personnes enseignantes au"travailler ensemble". Cette étude contribuera de façon significative à l'accroissement des connaissances au regard du"travailler ensemble" à l'école et en formation à l'enseignement dans le contexte de l'ÉPS. Cette perspective n'a pas ou très peu été documentée par d'autres auteurs. Bien qu'elle ne conduise pas à une série de recommandations à l'intention des acteurs impliqués dans la formation à l'enseignement, cette étude contribue, à clarifier des concepts liés au"travailler ensemble" et à les articuler."--Résumé abrégé par UMI.

Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene.

Complete achromatopsia is a rare autosomal recessive disease associated with CNGA3, CNGB3, GNAT2 and PDE6C mutations. This retinal disorder is characterized by complete loss of color discrimination due to the absence or alteration of the cones function. The purpose of the present study was the clinical and the genetic characterization of achromatopsia in a large consanguineous Tunisian family. Ophthalmic evaluation included a full clinical examination, color vision testing and electroretinography. Linkage analysis using microsatellite markers flanking CNGA3, CNGB3, GNAT2 and PDE6C genes was performed. Mutations were screened by direct sequencing. A total of 12 individuals were diagnosed with congenital complete achromatopsia. They are members of six nuclear consanguineous families belonging to the same large consanguineous family. Linkage analysis revealed linkage to GNAT2. Mutational screening of GNAT2 revealed three intronic variations c.119-69G>C, c.161+66A>T and c.875-31G>C that co-segregated with a novel mutation p.R313X. An identical GNAT2 haplotype segregating with this mutation was identified, indicating a founder mutation. All patients were homozygous for the p.R313X mutation. This is the first report of the clinical and genetic investigation of complete achromatopsia in North Africa and the largest family with recessive achromatopsia involving GNAT2; thus, providing a unique opportunity for genotype-phenotype correlation for this extremely rare condition.

Trabecular bone score in type 1 diabetes--a cross-sectional study.

UNLABELLED: Trabecular bone score (TBS) seems to provide additive value on BMD to identify individuals with prevalent fractures in T1D. TBS did not significantly differ between T1D patients and healthy controls, but TBS and HbA1c were independently associated with prevalent fractures in T1D. A TBS cutoff <1.42 reflected prevalent fractures with 91.7 % sensitivity and 43.2 % specificity. INTRODUCTION: Type 1 diabetes (T1D) increases the risk of osteoporotic fractures. TBS was recently proposed as an indirect measure of bone microarchitecture. This study aimed at investigating the TBS in T1D patients and healthy controls. Associations with prevalent fractures were tested. METHODS: One hundred nineteen T1D patients (59 males, 60 premenopausal females; mean age 43.4 ± 8.9 years) and 68 healthy controls matched for gender, age, and body mass index (BMI) were analyzed. The TBS was calculated in the lumbar region, based on two-dimensional (2D) projections of DXA assessments. RESULTS: TBS was 1.357 ± 0.129 in T1D patients and 1.389 ± 0.085 in controls (p = 0.075). T1D patients with prevalent fractures (n = 24) had a significantly lower TBS than T1D patients without fractures (1.309 ± 0.125 versus 1.370 ± 0.127, p = 0.04). The presence of fractures in T1D was associated with lower TBS (odds ratio = 0.024, 95 % confidence interval (CI) = 0.001-0.875; p = 0.042) but not with age or BMI. TBS and HbA1c were independently associated with fractures. The area-under-the curve (AUC) of TBS was similar to that of total hip BMD in discriminating T1D patients with or without prevalent fractures. In this set-up, a TBS cutoff <1.42 discriminated the presence of fractures with a sensitivity of 91.7 % and a specificity of 43.2 %. CONCLUSIONS: TBS values are lower in T1D patients with prevalent fractures, suggesting an alteration of bone strength in this subgroup of patients. Reliable TBS cutoffs for the prediction of fracture risk in T1D need to be determined in larger prospective studies.

L'Écho de Paris

1886/08/04 (Numéro 875).