Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Human skin penetration of silver nanoparticles through intact and damaged skin

7There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70g/cm2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24 h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ngcm−2 (range <LOD–2.23) and 2.32 ngcm−2 (range 0.43–11.6) were found in the receiving solutions of cells where the nanoparticles solution was applied on intact skin (eight cells) and on damaged skin (eight cells), respectively. Twenty-four hours silver flux permeation in damaged skin was 0.62±0.2 ngcm−2 with a lag time <1 h. Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very lowbut detectable, and that in case of damaged skin itwas possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy. We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system.There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70g/cm2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24 h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ngcm−2 (range <LOD–2.23) and 2.32 ngcm−2 (range 0.43–11.6) were found in the receiving solutions of cells where the nanoparticles solution was applied on intact skin (eight cells) and on damaged skin (eight cells), respectively. Twenty-four hours silver flux permeation in damaged skin was 0.62±0.2 ngcm−2 with a lag time <1 h. Our experimental data showed that silver nanoparticles absorption through intact and damaged skin was very lowbut detectable, and that in case of damaged skin itwas possible an increasing permeation of silver applied as nanoparticles. Moreover, silver nanoparticles could be detected in the stratum corneum and the outermost surface of the epidermis by electron microscopy. We demonstrated for the first time that silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the damaged skin in an in vitro diffusion cell system.nonemixedLARESE FILON F; D'AGOSTIN F; CROSERA M; ADAMI G.; RENZI N; BOVENZI M; MAINA GLARESE FILON, Francesca; D'Agostin, F; Crosera, Matteo; Adami, Gianpiero; Renzi, N; Bovenzi, Massimo; Maina, G

Targeted ablation of IKK2 improves skeletal muscle strength, maintains mass, and promotes regeneration

NF-\u3baB is a major pleiotropic transcription factor modulating immune, inflammatory, cell survival, and proliferative responses, yet the relevance of NF-\u3baB signaling in muscle physiology and disease is less well documented. Here we show that muscle-restricted NF-\u3baB inhibition in mice, through targeted deletion of the activating kinase inhibitor of NF-\u3baB kinase 2 (IKK2), shifted muscle fiber distribution and improved muscle force. In response to denervation, IKK2 depletion protected against atrophy, maintaining fiber type, size, and strength, increasing protein synthesis, and decreasing protein degradation. IKK2-depleted mice with a muscle-specific transgene expressing a local Igf-1 isoform (mIgf-1) showed enhanced protection against muscle atrophy. In response to muscle damage, IKK2 depletion facilitated skeletal muscle regeneration through enhanced satellite cell activation and reduced fibrosis. Our results establish IKK2/NF-\u3baB signaling as an important modulator of muscle homeostasis and suggest a combined role for IKK inhibitors and growth factors in the therapy of muscle diseases

Old age and other factors associated with salivary microbiome variation

BACKGROUND: Many factors can contribute to the exact makeup of the salivary microbiome. Differences in the oral microbiome occur with old age, which may be due to oral conditions and diseases associated with old age, such as edentulism, as well as other unknown causes. METHODS: The salivary microbiome was sampled in patients from a large urban clinic. For all subjects age, gender, periodontal status, caries status, presence of edentulism, medications, and tobacco usage were recorded. Multifactor analysis was used to study variation in salivary microbiome profiles linked to these factors. RESULTS: In the population sampled, there were significantly higher numbers of edentulous subjects, and increased levels of polypharmacy found with aging. Large differences in alpha diversity and beta diversity of the salivary microbiome in the old age group were largely linked to edentulism. However, multivariable analysis revealed, even after adjusting for differences in edentulism, polypharmacy, tobacco usage, periodontal disease, caries level, and gender, that old age itself was associated with lower levels of taxa Porphyromonas endodontalis, Alloprevotella tannerae, Filifactor alocis, Treponema, Lautropia Mirabilis and Pseudopropionibacterium sp._HMT_194. Surprisingly, of these taxa, most were ones known to reside on or near tooth surfaces. CONCLUSIONS: Another factor or factors beyond edentulism, polypharmacy and periodontal disease play a role in the differences seen in oral microbiome with old age. The nature of this factor(s) is not known

Salivary microbiome with gastroesophageal reflux disease and treatment

The effect of oral microbial composition on periodontal health and on systemic health has been, and is being established. The oral microbiome, in turn, can be altered by local and systemic diseases and conditions. Gastroesophageal reflux disease (GERD), has been associated with increased acidity in the oral cavity resulting in dental erosion, and controversially a reduced risk of periodontal disease. We hypothesized that presence of GERD was linked to a modified microbial profile in untreated GERD patients and that the use of proton pump inhibitor (PPI) drugs: potent disruptors of gut microbiome, in GERD patients might result in a salivary microbiome that is further distinct. Untreated GERD patients showed multiple differences in salivary microbiome as compared to healthy controls. Taxa found at lower levels related to the presence of GERD not treated by PPI included: Prevotella melaninogenica, Prevotella pallens, Leptotrichia, and Solobacterium moorei and thirteen others. In contrast, GERD patients chronically using PPI showed minimal differences in salivary taxa compared to healthy controls not using PPI

Traditional Craft Training and Demonstration in Museums

International audienceThis work regards the representation of handicrafts for craft training and demonstration in the environment of an ethnographic heritage museum. The craft of mastic cultivation is chosen as a use case. This paper presents the process of representation and presentation of this craft, following an articulated pipeline approach for data collection, annotation, and semantic representation. The outcomes were used to implement an exhibition that targets the presentation of craft context and craft training, through interactive experiences, mobile applications, and a hands-on training where users reenact the gestures of a mastic cultivator. Preliminary evaluation results show high acceptance for the installation and increased user interest

Multimodal Narratives for the Presentation of Silk Heritage in the Museum

International audienceIn this paper, a representation based on digital assets and semantic annotations is established for Traditional Craft instances, in a way that captures their socio-historic context and preserves both their tangible and intangible Cultural Heritage dimensions. These meaningful and documented experiential presentations are delivered to the target audience through narratives that address a range of uses, including personalized storytelling, interactive Augmented Reality (AR), augmented physical artifacts, Mixed Reality (MR) exhibitions, and the Web. The provided engaging cultural experiences have the potential to have an impact on interest growth and tourism, which can support Traditional Craft communities and institutions. A secondary impact is the attraction of new apprentices through training and demonstrations that guarantee long-term preservation. The proposed approach is demonstrated in the context of textile manufacturing as practiced by the community of the Haus der Seidenkultur, a former silk factory that was turned into a museum where the traditional craft of Jacquard weaving is still practiced