Integrin-linked kinase is required for TGF-_1 induction of dermal myofibroblast differentiation

Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-b (TGF-b) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-b1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-b1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as a-smooth muscle actin. These alterations were not limited to Smad-associated TGF-b1 responses, as stimulation of noncanonical mitogenactivated protein kinase pathways by this growth factor was also diminished in the absence of ILK. ILK-deficient fibroblasts exhibited abnormalities in the actin cytoskeleton, and did not form supermature focal adhesions or contractile F-actin stress fibers, indicating a severe impairment in their capacity to differentiate into myofibroblasts. These defects extended to the inability of cells to contract extracellular matrices when embedded in collagen lattices. We conclude that ILK is necessary to transduce signals implicated in the transition of dermal fibroblasts to myofibroblasts originating from matrix substrates and TGF-b1

Functioning in patients with schizophrenia: A systematic review of the literature using the International Classification of Functioning, Disability and Health (ICF) as a reference

Purpose: To identify and quantify the main concepts included in published studies focusing on individuals with schizophrenia using the International Classification of Functioning, Disability and Health (ICF). Methods: Searches (limited to those published from 2008 to 2012) were performed in MEDLINE, PsycINFO and CINAHL. Included studies described participants with schizophrenia, were original articles and included only subjects who were at least 18 years of age at study entry. All concepts underlying the measures and the text of the articles were extracted, and they were linked to ICF categories using standardized rules. Results: From the 3584 abstracts retrieved, 348 were randomly selected, and of these, 206 studies met the inclusion criteria. A total of 17,141 concepts were extracted, 84.8% of which could be linked to 491 ICF categories: 222 (45.21%) of the categories referred to Body Functions, 29 (5.91%) to Body Structures, 186 (37.88%) to Activities and Participation and 54 (11%) to Environmental Factors. Seventy second-level categories were reported in at least 5% of all studies: 30 of these categories referred to Body Functions, 2 to Body Structures, 34 to Activities and Participation and 4 to Environmental Factors. Conclusion: The study has allowed us to identify and quantify the main concepts included in studies focusing on people with schizophrenia using the ICF. The majority of the concepts refer to Body Functions and Activities and Participation, rather than to Body Structures and Environmental Factors

First report of Lonchaeidae (Diptera) infesting fruits of Byrsonima crassifolia in Brazil.

Murici, Byrsonima crassifolia (L.) Kunth (Malpighiaceae), is native to the Amazon region and several other regions of tropical America. The fruits are small globose drupes with fleshy yellow mesocarp (pulp) and characteristic flavor and aroma. They are consumed fresh as juice, jam, liquor and sweets (León 1968; Donadio et al. 2002; Lorenzi et al. 2006). In addition, fruits of this species have been widely used in the traditional medicine by its antimicrobial and antidepressant properties (Martínez-Vázquez et al. 1999; Herrera-Ruiz et al. 2011). The only record of fruit flies (Diptera) associated to fruits of B. crassifolia in Brazil was published by Pereira et al. (2008) from material collected in the state of Amapá during 2005 and 2006. In their work, a total number of 7,915 fruits (16.02 kg) was collected in 24 sampling points distributed in the municipalities of Macapá, Mazagão and Porto Grande. Three samples were infested by fruit flies of the family Tephritidae (one in Macapá, 0.01 puparia/fruit; two in Mazagão, 0.10 and 0.15 puparia/fruit). Anastrepha striata Schiner, 1868 (10 specimens), A. obliqua (Macquart, 1835) (8 specimens) and A. fraterculus (Wiedemann, 1830) (3 specimens) were recovered in those collections. In other samples of B. crassifolia collected in the Brazilian Amazon (states of Amapá and Rondônia), no fruit flies specimens were obtained (Deus et al. 2009; Pereira et al. 2010; Silva et al. 2011a). In Mexico, the presence of A. serpentina (Wiedemann, 1830) in B. crassifolia was recorded in the state of Chiapas (Aluja et al. 1987). However, the presence of Lonchaeidae (Diptera) species in B. crassifolia was not recorded in either study

Recombinant monovalent llama-derived antibody fragments (VHH) to rotavirus VP6 protect neonatal gnotobiotic piglets against human rotavirus-induced diarrhea

Group A Rotavirus (RVA) is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs) against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH) to protect against human rotavirus in gnotobiotic (Gn) piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256) for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.Fil: Vega, Celina Guadalupe. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vlasova, Anastasia N.. Ohio State University; Estados UnidosFil: Chattha, Kuldeep S.. Ohio State University; Estados UnidosFil: Gómez Sebastián, Silvia. Universidad Politécnica de Madrid; EspañaFil: Nuñez, Carmen. Universidad Politécnica de Madrid; EspañaFil: Alvarado, Carmen. Universidad Politécnica de Madrid; EspañaFil: Lasa, Rodrigo. Universidad Politécnica de Madrid; EspañaFil: Escribano, José M.. Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria. Departamento Mejora Genética y Biotecnología; EspañaFil: Garaicoechea, Lorena Laura. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Bok, Karin. National Institutes of Health; Estados UnidosFil: Wigdorovitz, Andrés. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Saif, Linda J.. Ohio State University; Estados UnidosFil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Robust iso-surface tracking for interactive character skinning

International audienceWe present a novel approach to interactive character skinning, which is robust to extreme character movements, handles skin contacts and produces the effect of skin elasticity (sliding). Our approach builds on the idea of implicit skinning in which the character is approximated by a 3D scalar field and mesh-vertices are appropriately re-projected. Instead of being bound by an initial skinning solution used to initialize the shape at each time step, we use the skin mesh to directly track iso-surfaces of the field over time. Technical problems are two-fold: firstly, all contact surfaces generated between skin parts should be captured as iso-surfaces of the implicit field; secondly, the tracking method should capture elastic skin effects when the joints bend, and as the character returns to its rest shape, so the skin must follow. Our solutions include: new composition operators enabling blending effects and local self-contact between implicit surfaces, as well as a tangential relaxation scheme derived from the as-rigid-as possible energy to solve the tracking problem

Impacto del proceso de enseñanza endoscópica en la detección de adenomas colónicos

ResumenAntecedentesEl impacto que el proceso de entrenamiento endoscópico ejerce sobre la calidad de la colonoscopia en un medio hispanoamericano es escasa.ObjetivoDeterminar el efecto del entrenamiento en la técnica de colonoscopia sobre la detección de adenomas.Materiales y métodosEntre julio del 2012 y julio del 2013, 3 médicos recibieron entrenamiento en colonoscopia por parte de 4 endoscopistas experimentados; Las colonoscopias realizadas por endoscopistas en entrenamiento supervisados fueron comparadas con aquellas realizadas por endoscopistas experimentados.ResultadosSe incluyeron 318 colonoscopias realizadas por alguno de los 3 endoscopistas en entrenamiento bajo supervisión y 367 realizadas por alguno de los endoscopistas entrenados. El análisis univariado mostró una diferencia no significativa en la tasa de detección de adenomas (30.4 vs. 24.7%; p = 0.09). En el análisis multivariado, la tasa de detección de adenomas fue significativamente mayor en las colonoscopias realizadas por alguno de los 3 endoscopistas en entrenamiento (odds ratio = 1.72 [1.19-2.48]).ConclusiónEl involucramiento de endoscopistas en formación tiene un efecto positivo sobre la detección de adenomas.AbstractBackgroundThere has been little reported experience in the Latin American hospital setting in relation to the impact of the endoscopic training process on colonoscopy quality.AimsTo determine the effect that training in the technique of colonoscopy has on adenoma detection in an Argentinian teaching hospital.Material and methodWithin the time frame of July 2012 and July 2013, 3 physicians received training in colonoscopy from 4 experienced endoscopists. The colonoscopies performed by the supervised trainees were compared with those carried out by the experienced endoscopists.ResultsA total of 318 colonoscopies performed by any one of the 3 supervised trainees and 367 carried out by any one of the experienced endoscopists were included. The univariate analysis showed a non-significant difference in the detection rate of adenomas (30.4 vs. 24.7%, P=.09). In the multivariate analysis, the detection rate of adenomas was significantly higher in the colonoscopies performed by one of the 3 trainees (odds ratio = 1.72 [1.19-2.48]).ConclusionsThe supervised involvement of endoscopic trainees has a positive effect on adenoma detection

Temperature dependence of underdense nanostructure formation in tungsten under helium irradiation

Recently, tungsten has been found to form a highly underdense nanostructured morphology ("W fuzz") when bombarded by an intense flux of He ions, but only in the temperature window 900-2000 K. Using object kinetic Monte Carlo simulations (pseudo-3D simulations) parameterized from first principles, we show that this temperature dependence can be understood based on He and point defect clustering, cluster growth, and detrapping reactions. At low temperatures (2300 K), all He is detrapped from clusters, preventing the formation of the large clusters that lead to fuzz growth in the intermediate temperature range. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein

KBG syndrome; Missense variants; Neurodevelopmental disordersSíndrome KBG; Variants de missense; Trastorns del neurodesenvolupamentSíndrome KBG; Variantes de missense; Trastornos del neurodesarrolloPurpose Although haploinsufficiency of ANKRD11 is among the most common genetic causes of neurodevelopmental disorders, the role of rare ANKRD11 missense variation remains unclear. We characterized clinical, molecular, and functional spectra of ANKRD11 missense variants. Methods We collected clinical information of individuals with ANKRD11 missense variants and evaluated phenotypic fit to KBG syndrome. We assessed pathogenicity of variants through in silico analyses and cell-based experiments. Results We identified 20 unique, mostly de novo, ANKRD11 missense variants in 29 individuals, presenting with syndromic neurodevelopmental disorders similar to KBG syndrome caused by ANKRD11 protein truncating variants or 16q24.3 microdeletions. Missense variants significantly clustered in repression domain 2 at the ANKRD11 C-terminus. Of the 10 functionally studied missense variants, 6 reduced ANKRD11 stability. One variant caused decreased proteasome degradation and loss of ANKRD11 transcriptional activity. Conclusion Our study indicates that pathogenic heterozygous ANKRD11 missense variants cause the clinically recognizable KBG syndrome. Disrupted transrepression capacity and reduced protein stability each independently lead to ANKRD11 loss-of-function, consistent with haploinsufficiency. This highlights the diagnostic relevance of ANKRD11 missense variants, but also poses diagnostic challenges because the KBG-associated phenotype may be mild and inherited pathogenic ANKRD11 (missense) variants are increasingly observed, warranting stringent variant classification and careful phenotyping

Near-infrared fluorescence imaging as an alternative to bioluminescent bacteria to monitor biomaterial-associated infections

Biomaterial-associated infection is one of the most common complications related with the implantation of any biomedical device. Several in vivo imaging platforms have emerged as powerful diagnostic tools to longitudinally monitor biomaterial-associated infections in small animal models. In this study, we directly compared two imaging approaches: bacteria engineered to produce luciferase to generate bioluminescence and reactive oxygen species (ROS) imaging of the inflammatory response associated with the infected implant. We performed longitudinal imaging of bioluminescence associated with bacteria strains expressing plasmid-integrated luciferase driven by different promoters or a strain with the luciferase gene integrated into the chromosome. These luminescent strains provided adequate signal for acute (0–4 days) monitoring of the infection, but the bioluminescence signal decreased over time and leveled off by 7 days post-implantation. This loss in bioluminescence signal was attributed to changes in the metabolic activity of the bacteria. In contrast, near-infrared fluorescence imaging of ROS associated with inflammation to the implant provided sensitive and dose-dependent signals of biomaterialassociated bacteria. ROS imaging exhibited higher sensitivity than the bioluminescence imaging and was independent of the bacteria strain. Near-infrared fluorescence imaging of inflammatory responses represents a powerful alternative to bioluminescence imaging for monitoring biomaterial-associated bacterial infections.This work was supported by the Ministerio of Economía y Competitividad (BIO2010-21049, 201120E092), the U.S.A. National Institutes of Health grant R21 AI094624 (A.J.G.), the Georgia Tech/Emory Center for the Engineering of Living Tissues, the Atlanta Clinical and Translational Science Institute under PHS Grant UL RR025008 from the Clinical and Translational Science Award Program