Inherited IL-17RC deficiency in patients with chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections of the skin, nail, oral, and genital mucosae with Candida species, mainly C. albicans. Autosomal-recessive (AR) IL-17RA and ACT1 deficiencies and autosomal-dominant IL-17F deficiency, each reported in a single kindred, underlie CMC in otherwise healthy patients. We report three patients from unrelated kindreds, aged 8, 12, and 37 yr with isolated CMC, who display AR IL-17RC deficiency. The patients are homozygous for different nonsense alleles that prevent the expression of IL-17RC on the cell surface. The defect is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. However, in contrast to what is observed for the IL-17RA– and ACT1-deficient patients tested, the response to IL-17E (IL-25) is maintained in these IL-17RC–deficient patients. These experiments of nature indicate that human IL-17RC is essential for mucocutaneous immunity to C. albicans but is otherwise largely redundant.In humans, chronic mucocutaneous candidiasis (CMC) is characterized by infections of the skin, nail, digestive, and genital mucosae with Candida species, mainly C. albicans, a commensal of the gastrointestinal tract in healthy individuals (Puel et al., 2012). CMC is frequent in acquired or inherited disorders involving profound T cell defects (Puel et al., 2010b; Vinh, 2011; Lionakis, 2012). Human IL-17 immunity has recently been shown to be essential for mucocutaneous protection against C. albicans (Puel et al., 2010b, 2012; Cypowyj et al., 2012; Engelhardt and Grimbacher, 2012; Huppler et al., 2012; Ling and Puel, 2014). Indeed, patients with primary immunodeficiencies and syndromic CMC have been shown to display impaired IL-17 immunity (Puel et al., 2010b). Most patients with autosomal-dominant (AD) hyper-IgE syndrome (AD-HIES) and STAT3 deficiency (de Beaucoudrey et al., 2008; Ma et al., 2008; Milner et al., 2008; Renner et al., 2008; Chandesris et al., 2012) and some patients with invasive fungal infection and autosomal-recessive (AR) CARD9 deficiency (Glocker et al., 2009; Lanternier et al., 2013) or Mendelian susceptibility to mycobacterial diseases (MSMD) and AR IL-12p40 or IL-12Rβ1 deficiency (de Beaucoudrey et al., 2008, 2010; Prando et al., 2013; Ouederni et al., 2014) have low proportions of IL-17A–producing T cells and CMC (Cypowyj et al., 2012; Puel et al., 2012). Patients with AR autoimmune polyendocrine syndrome type 1 (APS-1) and AIRE deficiency display CMC and high levels of neutralizing autoantibodies against IL-17A, IL-17F, and/or IL-22 (Browne and Holland, 2010; Husebye and Anderson, 2010; Kisand et al., 2010, 2011; Puel et al., 2010a).These findings paved the way for the discovery of the first genetic etiologies of CMC disease (CMCD), an inherited condition affecting individuals with none of the aforementioned primary immunodeficiencies (Puel et al., 2011; Casanova and Abel, 2013; Casanova et al., 2013, 2014). AR IL-17RA deficiency, AR ACT1 deficiency, and AD IL-17F deficiency were described, each in a single kindred (Puel et al., 2011; Boisson et al., 2013). A fourth genetic etiology of CMCD, which currently appears to be the most frequent, has also been reported: heterozygous gain-of-function (GOF) mutations of STAT1 impairing the development of IL-17–producing T cells (Liu et al., 2011; Smeekens et al., 2011; van de Veerdonk et al., 2011; Hori et al., 2012; Takezaki et al., 2012; Tóth et al., 2012; Al Rushood et al., 2013; Aldave et al., 2013; Romberg et al., 2013; Sampaio et al., 2013; Soltész et al., 2013; Uzel et al., 2013; Wildbaum et al., 2013; Frans et al., 2014; Kilic et al., 2014; Lee et al., 2014; Mekki et al., 2014; Mizoguchi et al., 2014; Sharfe et al., 2014; Yamazaki et al., 2014). We studied three unrelated patients with CMCD without mutations of IL17F, IL17RA, ACT1, or STAT1. We used a genome-wide approach based on whole-exome sequencing (WES). We found AR complete IL-17RC deficiency in all three patients.     

Effects of Hybridized Synthetic Fibers on the Shear Properties of Cement Composites

The use of fibers in cementitious composites yields numerous benefits due to their fiber-bridging capabilities in resisting cracks. Therefore, this study aimed to improve the shear-resisting capabilities of conventional concrete through the hybridization of multiple synthetic fibers, specifically on reinforced concrete structures in seismic-prone regions. For this study, 16 hybrid fiber-reinforced concretes (HyFRC) were developed from the different combinations of Ferro macro-synthetic fibers with the Ultra-Net, Super-Net, Econo-Net, and Nylo-Mono microfibers. These hybrids were tested under direct shear, resulting in improved shear strength of controlled specimens by Ferro-Ultra (32%), Ferro-Super (24%), Ferro-Econo (44%), and Ferro-Nylo (24%). Shear energy was further assessed to comprehend the effectiveness of the fiber interactions according to the mechanical properties, dosage, bonding power, manufactured material, and form of fibers. Conclusively, all fiber combinations used in this study produced positive synergistic effects under direct shear at large crack deformations.     

Magnetic and Tunable Sound Absorption Properties of an In-Situ Prepared Magnetorheological Foam

Conventional polyurethane foam has non-tunable sound absorption properties. Here, a magneto-induced foam, called magnetorheological (MR) foam, was fabricated with the feature of being able to tune sound absorption properties, primarily from the middle- to higher-frequency ranges. Three different samples of MR foams were fabricated in situ by varying the concentration of Carbonyl Iron Particles (CIPs) (0, 35, and 75 wt.%). The magnetization properties and tunable sound absorption characteristics were evaluated. From the magnetic saturation properties, the results showed very narrow and small coercivity of hysteresis loops relative to the soft magnetic properties of the CIPs. MR foam with 75 wt.% CIPs showed a higher magnetic saturation at 91.350 emu/g compared to MR foam with 35 wt.% CIPs at 63.896 emu/g. For tunable sound absorption testing, the effect of ‘shifting’ to higher frequency was also observed when the magnetic field was applied, which was ~10 Hz for MR foam with 35 wt.% CIPs and ~130 Hz for MR foam with 75 wt.% CIPs. As the latest evolution of semi-active noise control materials, the results from this study are valuable guidance for the advancement of MR-based devices.     

Effects of polyols on the quality characteristics of sucrose-free milk chocolate produced in a ball mill

Sucrose-free milk chocolates containing different types of bulk (isomalt, xylitol and maltitol) and high intensity (Stevia) sweeteners were produced by using a ball mill. The main quality characteristics of the formulated chocolates were evaluated and compared with those of the conventional sample containing sucrose. The Casson model was the best fitting model for the rheological data. Casson viscosity and Casson yield stress were significantly affected by the type of bulking agent in chocolates formulated with xylitol (p < 0.05). However xylitol notably improved the overall acceptability according to the sensory analysis results. Chocolates containing the sucrose replacers demonstrated lower T_onset values and higher enthalpy than the control sample. Sucrose-free chocolates illustrated a higher degree of particle agglomeration. Bulk sweeteners meanwhile seem to have high potential for milk chocolate production with low calorie values by using the ball mill technique. Industrial applications: the production of sucrose-free chocolates with conventional methods requires a lot of time and energy. Recently, using alternative methods for chocolate production has been raising interest in many small industries. This study proposed a ball mill method for the preparation of sucrose-free milk chocolates with physiochemical properties almost ranging in the standard limit defined for chocolate. Although using the ball mill method presents a more cost-effective technique for chocolate production and provides shorter processing times for small chocolate industries, it seems to be less efficient in evaporating moisture than the conventional processing. Challenges are still ahead for upgrading this alternative technique to be efficient in evaporating more moisture during operation ending in a high quality product.

Sucrose-free milk chocolates containing different types of bulk (isomalt, xylitol and maltitol) and high intensity (Stevia) sweeteners were produced by using a ball mill.