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

Kinetics of the pollutant photocatalytic conversion in a Photo-CREC-Air Reactor

This research reports the kinetic studies for acetone and acetaldehyde photoconversion in the gas phase utilizing a scaled-up Photo-CREC-Air unit with TiO2. The inclusion of intermediate species in the reaction network is required for the kinetic modeling of a wide range of oxygenate pollutant concentrations. The proposed ‘‘in parallel-series” reaction network encompasses a Langmuir-Hinshelwood (L-H) kinetics including species adsorption and intrinsic reaction parameters. The estimated kinetic parameters provide a successful prediction of various measurable chemical species. It is shown that the proposed kinetic model can be simplified, under low initial model pollutant concentrations. This is critical to avoid model overparameterization. The proposed kinetic model while being restricted to two model pollutants (ace- tone and acetaldehyde) and one specific photoreactor (e.g. 55.1 L Photo-CREC-Air), provides a framework to establish the photodegradation kinetics of other organic species in air, for larger photoreactor scales

Kerker Conditions Upon Lossless, Absorption, and Optical Gain Regimes

The directionality and polarization of light show peculiar properties when the scattering by a dielectric sphere can be described exclusively by electric and magnetic dipolar modes. Particularly, when these modes oscillate in-phase with equal amplitude, at the so-called first Kerker condition, the zero optical backscattering condition emerges for non-dissipating spheres. However, the role of absorption and optical gain in the first Kerker condition remains unexplored. In this work, we demonstrate that either absorption or optical gain precludes the first Kerker condition and, hence, the absence of backscattered radiation light, regardless of the size of the particle, incident wavelength, and incoming polarization. Finally, we derive the necessary prerequisites of the second Kerker condition of the zero forward light scattering, finding that optical gain is a compulsory requirement

New algorithm for the elucidation of functional properties of gelatin-based materials

In the present work, fish gelatin was employed to develop renewable and biodegradable materials, reducing environmental problems associated with conventional petroleum-based materials. Glycerol was used as plasticizer and gallic acid was added in order to enhance the functional properties of the material. L-fuzzy concept analysis was applied for modelling the formulations and properties of the films. These new methodology is used in the design of the material avoiding the traditional inefficient trial an error approach usually employed. Two applications of the developed bio-based material were analyzed: fatty food packaging application in food area and wound healing in the biomedical field. The functional properties requirements of water contact angle (CA), water vapour transmission rate (WVTR), colour L * and b * values, tensile strength (TS), elongation at break (EB) and gloss values were specified for both applications. Applying the proposed algorithm, the required formulations were estimated and the experimental results showed a high accordance with the predicted values of the final properties, as well as with the requirements. This analysis allowed finding the required formulations in a highly cost-effective wayThe authors thank the research groups from the Basque Gov-ernment (IT1256-19) and the University of the Basque Country UPV/EHU (GIU18/154) . This work was financially supported by the Basque Government (KK2019/00006) . Documen

Base Pairing Interaction between 5′- and 3′-UTRs Controls icaR mRNA Translation in Staphylococcus aureus

The presence of regulatory sequences in the 3′ untranslated region (3′-UTR) of eukaryotic mRNAs controlling RNA stability and translation efficiency is widely recognized. In contrast, the relevance of 3′-UTRs in bacterial mRNA functionality has been disregarded. Here, we report evidences showing that around one-third of the mapped mRNAs of the major human pathogen Staphylococcus aureus carry 3′-UTRs longer than 100-nt and thus, potential regulatory functions. We selected the long 3′-UTR of icaR, which codes for the repressor of the main exopolysaccharidic compound of the S. aureus biofilm matrix, to evaluate the role that 3′-UTRs may play in controlling mRNA expression. We showed that base pairing between the 3′-UTR and the Shine-Dalgarno (SD) region of icaR mRNA interferes with the translation initiation complex and generates a double-stranded substrate for RNase III. Deletion or substitution of the motif (UCCCCUG) within icaR 3′-UTR was sufficient to abolish this interaction and resulted in the accumulation of IcaR repressor and inhibition of biofilm development. Our findings provide a singular example of a new potential post-transcriptional regulatory mechanism to modulate bacterial gene expression through the interaction of a 3′-UTR with the 5′-UTR of the same mRNA. © 2013 Ruiz de los Mozos et al.Peer Reviewe

Development of a Genetic Risk Score to predict the risk of overweight and obesity in European adolescents from the HELENA study

Obesity is the result of interactions between genes and environmental factors. Since monogenic etiology is only known in some obesity-related genes, a genetic risk score (GRS) could be useful to determine the genetic predisposition to obesity. Therefore, the aim of our study was to build a GRS able to predict genetic predisposition to overweight and obesity in European adolescents. A total of 1069 adolescents (51.3% female), aged 11–19 years participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were genotyped. The sample was divided in non-overweight (non-OW) and overweight/obesity (OW/OB). From 611 single nucleotide polymorphisms (SNP) available, a first screening of 104 SNPs univariately associated with obesity (p < 0.20) was established selecting 21 significant SNPs (p < 0.05) in the multivariate model. Unweighted GRS (uGRS) was calculated by summing the number of risk alleles and weighted GRS (wGRS) by multiplying the risk alleles to each estimated coefficient. The area under curve (AUC) was calculated in uGRS (0.723) and wGRS (0.734) using tenfold internal cross-validation. Both uGRS and wGRS were significantly associated with body mass index (BMI) (p < .001). Both GRSs could potentially be considered as useful genetic tools to evaluate individual’s predisposition to overweight/obesity in European adolescents.European Commission FOOD-CT-2005-007034HELENA projectSpanish Ministry of Economy and Competitiveness RYC-2010-05957 RYC2011-09011Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn)Iberus Talent Pre-doctoral fellowships under the European Union 801586Instituto de Salud Carlos III CB15/0004

Clinical consequences of BRCA2 hypomorphism

Altres ajuts: Asociación Española contra el Cáncer (LABAE16020PORTT)Altres ajuts: Asociación Española contra el Cáncer (ERAPERMED2019-215)The tumor suppressor FANCD1/BRCA2 is crucial for DNA homologous recombination repair (HRR). BRCA2 biallelic pathogenic variants result in a severe form of Fanconi anemia (FA) syndrome, whereas monoallelic pathogenic variants cause mainly hereditary breast and ovarian cancer predisposition. For decades, the co-occurrence in trans with a clearly pathogenic variant led to assume that the other allele was benign. However, here we show a patient with biallelic BRCA2 (c.1813dup and c.7796 A > G) diagnosed at age 33 with FA after a hypertoxic reaction to chemotherapy during breast cancer treatment. After DNA damage, patient cells displayed intermediate chromosome fragility, reduced survival, cell cycle defects, and significantly decreased RAD51 foci formation. With a newly developed cell-based flow cytometric assay, we measured single BRCA2 allele contributions to HRR, and found that expression of the missense allele in a BRCA2 KO cellular background partially recovered HRR activity. Our data suggest that a hypomorphic BRCA2 allele retaining 37-54% of normal HRR function can prevent FA clinical phenotype, but not the early onset of breast cancer and severe hypersensitivity to chemotherapy

Mediterranean diet, screen-time-based sedentary behavior and their interaction effect on adiposity in European adolescents: The HELENA study

Childhood obesity is a worldwide epidemic. Mediterranean diet (MD) is inversely associated with childhood obesity, but the interaction with other environmental factors, such screen time, might influence the health benefits of a high MD adherence in adolescents. The aim of the present study was to assess whether an association between MD and screen time exists in European adolescents. Moreover, we also explored whether sedentary time has a modulatory effect on the association between MD and adiposity. Adherence to the MD (24 h recalls), screen time (questionnaire), pubertal development, body mass index (BMI), fat mass index (FMI) and waist circumference (WC) were evaluated in 2053 adolescents (54.7% females), aged 12.5–17.5 years. In females, MD adherence was associated with lower BMI and FMI only when they were exposed to less than 338 min/day of screen time (81.8% of females); MD adherence was also associated with lower WC only when females were exposed to less than 143 min/day of screen time (31.5% of females). No significant MD-screen time interaction was observed in males. In conclusion, screen-time-based sedentary behaviours had a modulatory effect in the association between MD adherence and adiposity in European female adolescents

Sensory deprivation in Staphylococcus aureus

Bacteria use two-component systems (TCSs) to sense and respond to environmental changes. The core genome of the major human pathogen Staphylococcus aureus encodes 16 TCSs, one of which (WalRK) is essential. Here we show that S. aureus can be deprived of its complete sensorial TCS network and still survive under growth arrest conditions similarly to wild-type bacteria. Under replicating conditions, however, the WalRK system is necessary and sufficient to maintain bacterial growth, indicating that sensing through TCSs is mostly dispensable for living under constant environmental conditions. Characterization of S. aureus derivatives containing individual TCSs reveals that each TCS appears to be autonomous and self-sufficient to sense and respond to specific environmental cues, although some level of cross-regulation between non-cognate sensor-response regulator pairs occurs in vivo. This organization, if confirmed in other bacterial species, may provide a general evolutionarily mechanism for flexible bacterial adaptation to life in new niches.This work was supported by the Spanish Ministry of Economy and Competitiveness grants BIO2011-30503-C02-02, BIO2014-53530-R, SAF2014-56716-REDT, and RTC-2015-3184-1. J.V. was supported by Ramon y Cajal (RYC-2009-03948) contract from the Spanish Ministry of Economy and Competitiveness

The extradomain a of fibronectin enhances the efficacy of lipopolysaccharide defective Salmonella bacterins as vaccines in mice

The Extradomain A from fibronectin (EDA) has an immunomodulatory role as fusion protein with viral and tumor antigens, but its effect when administered with bacteria has not been assessed. Here, we investigated the adjuvant effect of EDA in mice immunizations against Salmonella enterica subspecies enterica serovar Enteritidis (Salmonella Enteritidis). Since lipopolysaccharide (LPS) is a major virulence factor and the LPS O-polysaccharide (O-PS) is the immunodominant antigen in serological diagnostic tests, Salmonella mutants lacking O-PS (rough mutants) represent an interesting approach for developing new vaccines and diagnostic tests to differentiate infected and vaccinated animals (DIVA tests). Here, antigenic preparations (hot-saline extracts and formalin-inactivated bacterins) from two Salmonella Enteritidis rough mutants, carrying either intact (SE Delta waaL) or deep-defective (SE Delta gal) LPS-Core, were used in combination with EDA. Biotinylated bacterins, in particular SE Delta waaL bacterin, decorated with EDAvidin (EDA and streptavidin fusion protein) improved the protection conferred by hot-saline or bacterins alone and prevented significantly the virulent infection at least to the levels of live attenuated rough mutants. These findings demonstrate the adjuvant effect of EDAvidin when administered with biotinylated bacterins from Salmonella Enteritidis lacking O-PS and the usefulness of BEDA-SE Delta waaL as non-live vaccine in the mouse model.This work was funded by Gobierno de Navarra and European Union (project EuroInnova-Navarra reference IIM10865.RI1-EP12). B.S.R., P.M.M. and X.D.A. post-doctoral contracts were granted by Gobierno de Navarra/JAE-doc CSIC, MICINN (Subprograma Juan de la Cierva) and Universidad Pública de Navarra, respectively