From Chihuahua to Saint-Bernard: how did digestion and microbiota evolve with dog sizes

Health and well-being of dogs are of paramount importance to their owners. Digestion plays a key role in dog health, involving physicochemical, mechanical and microbial actors. However, decades of breeding selection led to various dog sizes associated with different digestive physiology and disease sensitivity. Developing new products requires the consideration of all the multi-faceted aspects of canine digestion, the evaluation of food digestibility, drug release and absorption in the gut. This review paper provides an exhaustive literature survey on canine digestive physiology, focusing on size effect on anatomy and digestive parameters, with graphical representation of data classified as “small”, “medium” and “large” dogs. Despite the huge variability between protocols and animals, interesting size effects on gastrointestinal physiology were highlighted, mainly related to the colonic compartment. Colonic measurements, transit time permeability, fibre degradation, faecal short-chain fatty acid concentration and faecal water content increase while faecal bile acid concentration decreases with body size. A negative correlation between body weight and Proteobacteria relative abundance was observed suggesting an effect of dog body size on faecal microbiota. This paper gathers helpful in vivo data for academics and industrials and supports the development of new food and pharma products to move towards canine personalized nutrition and health

Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH

Abstract: Background: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. Methods: To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource – Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. Results: Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e−5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. Conclusions: Rare variant analysis of a large international consortium identified two new candidate genes—FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants

Functionalization of CoCr surfaces for cardiovascular applications

Mobilitat-IncomingCardiovascular diseases are major concerns in public health of developed countries and the first cause of death in the world. The treatment of coronary artery diseases using metallic stents has been one of the most revolutionary and most rapidly adopted medical interventions of these last years. During early development much of the investigation and debate revolved around stent design, including assessment of different materials and surface treatments. However, restenosis, incomplete endothelialization, and thrombosis hamper the long term clinical success. The biological events that lead to the appropriate response of already successfully proved biomaterial surfaces, such as Co-Cr alloy for cardiovascular stents, are mainly influenced by the interactions at the bio/non-bio interface. To improve the endothelial cells adhesion and growth, surface treatments have been developed to anchor REDV elastin-like polymers which enhances surface endothelization . The aim of the present project is to obtain a new family of biofunctionalized Co‐Cr alloy surface by covalently-anchoring the REDV elastin-like polymer. Different surface treatments have been performed on CoCr: O2 plasma treatment, silanization with CPTES and NaOH basic etching previously to chemically or physically attach the biopolymer. Then surface characterization has been performed, for each step, in termsof surface wettability, roughness, topography, chemistry, and charge. A biochemist characterization has been done to quantify the adsorbed biopolymer by means of fluorescent assays to evaluate the efficiency of the surface treatments. CoCr alloy surfaces were successfully biofunctionalized with REDV elastin–like polymer. The quantity of adsorbed biopolymer was influenced by surface characteristics. All surfaces revealed considerable quantities of attached biopolymer, but combination of NaOH+CPTES series attached the highest amount (0,008 μg/mm2± 0,002) compared to NaOH series (0,005 μg/mm2± 0,003), CPTES series (0,004 μg/mm2± 0,001), control samples (0,003 μg/mm2± 0,001) and O2 plasma series (0,002 μg/mm2± 0, 0005). The quantity of hydroxiles formed on the different surfaces influences biopolymer adsorption and then, cell response

Functionalization of CoCr surfaces for cardiovascular applications

Mobilitat-IncomingCardiovascular diseases are major concerns in public health of developed countries and the first cause of death in the world. The treatment of coronary artery diseases using metallic stents has been one of the most revolutionary and most rapidly adopted medical interventions of these last years. During early development much of the investigation and debate revolved around stent design, including assessment of different materials and surface treatments. However, restenosis, incomplete endothelialization, and thrombosis hamper the long term clinical success. The biological events that lead to the appropriate response of already successfully proved biomaterial surfaces, such as Co-Cr alloy for cardiovascular stents, are mainly influenced by the interactions at the bio/non-bio interface. To improve the endothelial cells adhesion and growth, surface treatments have been developed to anchor REDV elastin-like polymers which enhances surface endothelization . The aim of the present project is to obtain a new family of biofunctionalized Co‐Cr alloy surface by covalently-anchoring the REDV elastin-like polymer. Different surface treatments have been performed on CoCr: O2 plasma treatment, silanization with CPTES and NaOH basic etching previously to chemically or physically attach the biopolymer. Then surface characterization has been performed, for each step, in termsof surface wettability, roughness, topography, chemistry, and charge. A biochemist characterization has been done to quantify the adsorbed biopolymer by means of fluorescent assays to evaluate the efficiency of the surface treatments. CoCr alloy surfaces were successfully biofunctionalized with REDV elastin–like polymer. The quantity of adsorbed biopolymer was influenced by surface characteristics. All surfaces revealed considerable quantities of attached biopolymer, but combination of NaOH+CPTES series attached the highest amount (0,008 μg/mm2± 0,002) compared to NaOH series (0,005 μg/mm2± 0,003), CPTES series (0,004 μg/mm2± 0,001), control samples (0,003 μg/mm2± 0,001) and O2 plasma series (0,002 μg/mm2± 0, 0005). The quantity of hydroxiles formed on the different surfaces influences biopolymer adsorption and then, cell response

In vitro models of the canine digestive tract as an alternative to in vivo assays: Advances and current challenges

Dogs occupy a full place in the family, and their well-being is of paramount importance to their owners. Digestion, a complex process involving physicochemical, mechanical, and microbial parameters, plays a central role in maintaining canine health. As in vivo studies in dogs are increasingly restricted by ethical, regulatory, societal, and cost pressures, an alternative option is the use of in vitro models simulating the different compartments of the canine gastrointestinal tract. This review introduces digestion and gut microbiota as key factors in dog nutrition and health under both healthy and diseased conditions (obesity and inflammatory bowel disease) and highlights similarities and differences between the human and canine digestive tract and processes. We provide the first in-depth description of currently available models of the canine digestive tract, discuss technical and scientific challenges that need to be addressed, and introduce potential applications of in vitro gut models in the food and veterinary fields. Even if the development of some in vitro models is still limited by a lack of in vivo data in dogs that is necessary for relevant configuration and validation, translation of long-term expertise on human in vitro gut models to dogs opens avenues for model optimization and adaptation to specific canine digestive conditions associated with various dog ages, sizes, breeds and/or diets, in both physiological and diseased states

Aqueous Cr(VI) reduction by pyrite: Speciation and characterisation of the solid phases by X-ray photoelectron, Raman and X-ray absorption spectroscopies

International audienceOptical microscopy, confocal Raman micro-spectrometry, X-ray photoelectron micro-spectroscopy (XPS) and synchrotron based micro-X-ray fluorescence (XRF), micro-X-ray absorption near edge spectroscopy (XANES) and micro-extended X-ray absorption fine structure (EXAFS) were used to investigate the reduction of aqueous Cr(VI) by pyrite. Special emphasis was placed on the characterisation of the solid phase formed during the reaction process. Cr(III) and Fe(III) species were identified by XPS analyses in addition to non-oxidised pyrite. Optical microscopy images and the corresponding Raman spectra reveal a strong heterogeneity of the samples with three different types of zones. (i) Reflective areas with Eg and Ag Raman wavenumbers relative to non-oxidised pyrite are the most frequently observed. (ii) Orange areas that display a drift of the Eg and Ag pyrite vibration modes of −3 and −6 cm−1, respectively. Such areas are only observed in the presence of Cr(VI) but are not specifically due to this oxidant. (iii) Bluish areas with vibration modes relative to a corundum-like structure that can be assigned to a solid solution Fe2−xCrxO3, x varying between 0.2 and 1.5. The heterogeneity in the spatial distribution of chromium observed by optical microscopy and associated Raman microspectroscopy is confirmed by μ-XRF. In agreement with both solution and XPS analyses, these spectroscopies clearly confirm that chromium is in the trivalent state. XANES spectra in the iron K-edge pre-edge region obtained in rich chromium areas reveal the presence of ferric ion thus revealing a systematic association between Cr(III) and Fe(III). In agreement with Raman analyses, Cr K-edge EXAFS can be interpreted as corresponding to Cr atoms involved in a substituted-type hematite structure Fe2−xCrxO3

Systèmes digestifs artificiels : applications en nutrition et santé canine

De nombreuses études ont démontré l'importance de la digestion et du microbiote intestinal dans la nutrition et la santé des chiens. Les systèmes digestifs artificiels représentent une alternative pertinente aux essais in vivo, en accord avec la règlementation européenne des 3Rs. Aujourd’hui, une dizaine de modèles in vitro statiques ou dynamiques reproduisant une ou plusieurs parties du tractus gastro-intestinal du chien ont été développés, en prenant en compte les paramètres physico-chimiques, mécaniques et/ou microbiens de la digestion canine. Ces modèles permettent d’étudier en laboratoire le devenir de produits alimentaires et vétérinaires dans l'environnement digestif du chien, notamment en termes de digestibilité des macronutriments, bioaccessibilité de micronutriments, survie et activité de microorganismes ou pharmacocinétique des médicaments. Afin d’élargir leurs potentiels, ces modèles pourront dans un futur proche être couplés à des modèles cellulaires ou être adaptés pour reproduire des conditions pathologiques comme l’obésité. Mots clés : modèle digestif in vitro, chien, nutrition, santé, microbiot

Ni(II) and Co(II) bis(acetylacetonato) complexes for alkene/vinylsilane silylation and silicone crosslinking

International audienceCommercially available Ni(II) and Co(II) complexes – M(acac)2 (acac = acetylacetonate) and M(tmhd)2 (tmhd = 2,2,6,6-tetramethyl-3,5-heptanedionato) – exhibit catalytic activity for alkene/vinylsilane dehydrogenative silylation (DS) and hydrosilylation (HS) with tertiary silanes without the use of any external reducing agents. Using the model compounds divinyltetramethylsiloxane a.k.a dvtms and vinylpentamethyldisiloxane a.k.a vpmds, different selectivities (HS, DS, undesired non-C–Si bond-forming reactions…) are observed whether nickel or cobalt catalysts are employed, with Ni being DS-selective and Co yielding bothHS and DS products. All four complexes are efficient at thermally inducing silicone-oil crosslinking under a non-inert atmosphere, and promote metal-dependent selectivity that is slightly different from model reactions, which HR-MAS NMR spectroscopy unveils. Additional observations as well as NMR studies of [Ni(tmhd)2 + reagent] mixtures provide some insights into the possible activation pathways

Colonic physicochemical parameters from different dog’s sizes reshape canine microbiota activity and structure in an in vitro gut model

International audienceCanine digestion is a complex and regionalized process involving physicochemical, mechanical, and microbial aspects, playing a key role in maintaining dog health. However, decades of breeding selection are associated to variations in dog’s size, digestive physiology, and disease sensitivity.To reproduce the colonic environmental conditions from three dog’s sizes in vitro, we reviewed the literature to determine canine ileal effluent composition, colonic pH and transit time of small, medium and large dogs. The one stage fermentation system M-ARCOL (Mucosal Artificial Colon) was set-up with those different parameters and bioreactors reproducing the three dog’s size conditions were inoculated with the same fecal sample and ran in parallel for 8 days. Two biological replicates were performed with faecal samples from one male and one female of medium size. Microbiota activity was followed by daily analysis of gas and short-chain fatty acid composition and production. Quantitative PCR (total bacteria) and Illumina 16S sequencing were performed to investigate the structure of luminal and mucus-associated microbiota.Small, medium, and large conditions led to three different profiles. Gas production increased with dog’s size and the same significant positive correlation was observed with total SCFA production, and acetate and butyrate ratios, reflecting the longer fermentation time in large dog colon. qPCR analysis showed a decrease in total bacteria amount from small to large conditions, but influence of dog size on microbiota structure will be confirmed by ongoing Illumina sequencing analysis.To conclude, the sole colonic physicochemical parameters seem to be able to reshape canine microbiota activity and composition. In a next step, bioreactors set with small, medium, and large parameters will be inoculated with corresponding dog faeces to complete the development of in vitro gut models for each dog size and validate them by comparing in vitro results with in vivo data in dogs