Estudio gonioscópico del ángulo iridocorneal del Perro de Agua Español

Realizamos un estudio gonioscópico de 46 Perros de Agua Español sanos, apreciando un ángulo iridocorneal abierto en todos los cuadrantes. Describimos las diferentes estructuras del ángulo iridocorneal en esta raza: las dos filas de fibras. del ligamento pectinado, la red trabecular uveal con los espacios de Fontana, y las bandas pigmentadas superficial y profunda. El ángulo iridocorneal en el Perro de Agua Español no presenta características peculiares para esta raza. Hemos observado grandes diferencias entre ojos de distintos perros, menores entre los del mismo perro, y escasas entre los distintos cuadrantes del mismo ojo. El grado de pigmentación de las estructuras del ángulo iridocorneal no depende del sexo ni de la edad, sino sólo de la pigmentación de la capa y del iris.In the present work, we have realized a gonioscopic study in 46 Spanish Water's Dogs. We have seen an iridocorneal angle always open in all quadrants and we have noticed different structures of the iridocorneal angie. the two rows of fibres of the pectinate ligament, the uveal trabecular meshwork with the Fontana's spaces and the deep and superficial pigrnent bands. The iridocorneal angle of the Spanish Water's Dog does not exhibit peculiar characteristics for this race. We have observed large differences between eyes of different dogs, lesser differences between the eyes of the same dog, and rares differences between the different quadrants of the same eye. We have found that the degree of pigmentation of the structures of iridocorneal angle does not depend of the age, only of the pigmentation of the coat and iris

Paper del sistema GAS6-TAM en el remodelat ventricular post infart agut de miocardi

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Small Molecules as Toll-like Receptor 4 Modulators Drug and In-House Computational Repurposing

The innate immunity toll-like receptor 4 (TLR4) system is a receptor of paramount importance as a therapeutic target. Virtual screening following a “computer-aided drug repurposing” approach was applied to the discovery of novel TLR4 modulators with a non-lipopolysaccharide-like structure. We screened almost 29,000 approved drugs and drug-like molecules from commercial, public, and in-house academia chemical libraries and, after biological assays, identified several compounds with TLR4 antagonist activity. Our computational protocol showed to be a robust approach for the identification of hits with drug-like scaffolds as possible inhibitors of the TLR4 innate immune pathways. Our collaborative work broadens the chemical diversity for inspiration of new classes of TLR4 modulators.This work was financially supported by the Spanish Ministry for Science and Innovation (grants CTQ2014-57141-R, CTQ2017-88353-R, and PID2020-113588RB-I00 for S.M.S.; grants BES-2012-053653 for L.P.R., BES-2015-071588 for J.G.C. and PID2021-124983OB-I00 for J.C.M.), the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (MINECO/FEDER; SAF2016-75988-R), and the Community of Madrid (S-2010/BMD-2332) for M.F

Unveiling Molecular Recognition of Sialoglycans by Human Siglec-10

29 p.-6 fig.-2 tab.-7 fig. supl.-2 tab. supl.-1 graph. abst.Siglec-10 is an inhibitory I-type lectin selectively recognizing sialoglycans exposed on cell surfaces, involved in several patho-physiological processes. The key role Siglec-10 plays in the regulation of immune cell functions has made it a potential target for the development of immunotherapeutics against a broad range of diseases. However, the crystal structure of the protein has not been resolved for the time being and the atomic description of Siglec-10 interactions with complex glycans has not been previously unraveled. We present here the first insights of the molecular mechanisms regulating the interaction between Siglec-10 and naturally occurring sialoglycans. We used combined spectroscopic, computational and biophysical approaches to dissect glycans' epitope mapping and conformation upon binding in order to afford a description of the 3D complexes. Our outcomes provide a structural perspective for the rational design and development of high-affinity ligands to control the receptor functionality.This study was supported by the project ‘‘GLYTUNES’’ funded by MIUR Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN 2017) (2017XZ2ZBK, 2019–2022) to A.S.; by progetto POR SATIN and Progetto POR CampaniaOncoterapia to A.M.; by the European Commission (H2020-MSCA- 814102-SWEET CROSSTALK project) to A.M., R.M., and A.S.. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement No 851356 to R.M. FSE,PON Ricerca e Innovazione 2014–2020, Azione I.1 ‘‘Dottorati Innovativi con caratterizzazione Industriale’’ is acknowledged for funding the PhD grant to R.E.F. Grants by the Spanish Ministry of Science MICINN (CTQ2017-88353-R and fellowship BES 2015–071588 to J.G.-C.) and Wellcome Trust 103744/Z/14/Z to P.R.C. are acknowledged.Peer reviewe

Invasive pulmonary aspergillosis in heart transplant recipients: Is mortality decreasing

Introduction: Infection remains a major complication among heart transplant (HT) recipients, causing approximately 20% of deaths in the first year after transplantation. In this population, Aspergillus spp. can have various clinical presentations including invasive pulmonary aspergillosis (IPA), with high mortality (53-78%). Objectives: To establish the characteristics of IPA infection in HT recipients and their outcomes in our center. Methods: Among 328 HTs performed in our center between 1998 and 2016, we identified five cases of IPA. Patient medical records were examined and clinical variables were extracted. Results: All cases were male, and mean age was 62 years. The most common indication for HT was non-ischemic dilated cardiomyopathy. Productive cough was reported as the main symptom. The radiological assessment was based on chest X-ray and chest computed tomography. The most commonly reported radiographic abnormality was multiple nodular opacities in both techniques. Bronchoscopy was performed in all patients and Aspergillus fumigatus was isolated in four cases on bronchoalveolar lavage culture. Treatment included amphotericin in four patients, subsequently changed to voriconazole in three, and posaconazole in one patient, with total treatment lasting an average of 12 months. Neutropenia was found in only one patient, renal failure was observed in two patients, and concurrent cytomegalovirus infection in three patients. All patients were alive after a mean follow-up of 18 months. Conclusions: IPA is a potentially lethal complication after HT. Early diagnosis and prompt initiation of aggressive treatment are the cornerstone of better survival

Die Rolle des Freibergerpferdes im Pferdemarkt Schweiz

Das Freiberger Pferd hat wie viele andere vergleichbare lokale, ursprüngliche europäische Pferderassen mit rückläufigen Bestandes- und Geburtenzahlen sowie einer fehlenden Rentabilität auf Stufe Produktion zu kämpfen. Agroscope, Schweizer Nationalgestüt SNG, untersuchte im Zuge der Erarbeitung eines Strategierapportes zur Erhaltung der Freibergerrasse die Marktkonformität des Freibergerpferdes (FM: franches-montagnes) mittels einer Umfrage bei Pferdeeigentümern sowie ergänzenden Experteninterviews. Die Ergebnisse lassen den Schluss zu, dass bei einer Mehrheit der befragten Pferdeeigentümer die persönlichen Erwartungen an ein Pferd mit der Beurteilung der Qualitäten und der generellen Wahrnehmung des Freibergerpferdes deckungsgleich sind. Daraus lässt sich ableiten, dass der FM über Qualitäten verfügt, die im Grundsatz im Freizeitpferdemarkt nachgefragt werden (einfacher Charakter, Polyvalenz, Robustheit, Gesundheit). Das Image des Markenbildes FM ist bei den nicht FM-Besitzern deutlich weniger positiv als bei den FM-Besitzern. Die Ergebnisse der Umfrage sowie der Experteninterviews zeigten, dass vor allem Anstrengungen zur Verbesserung der Vermarktung und des Images notwendig sind, um einen besseren Absatz von Freibergerpferden zu gewährleisten und damit auch langfristig einen Anstieg der Geburten zu erreichen

Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development

The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D) growth conditions using non-transformed prostate epithelial cells (EP156T), an androgen-sensitive prostate cancer cell line (LNCaP), and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D) growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.</p

An Ultra-Fast Metabolite Prediction Algorithm

Small molecules are central to all biological processes and metabolomics becoming an increasingly important discovery tool. Robust, accurate and efficient experimental approaches are critical to supporting and validating predictions from post-genomic studies. To accurately predict metabolic changes and dynamics, experimental design requires multiple biological replicates and usually multiple treatments. Mass spectra from each run are processed and metabolite features are extracted. Because of machine resolution and variation in replicates, one metabolite may have different implementations (values) of retention time and mass in different spectra. A major impediment to effectively utilizing untargeted metabolomics data is ensuring accurate spectral alignment, enabling precise recognition of features (metabolites) across spectra. Existing alignment algorithms use either a global merge strategy or a local merge strategy. The former delivers an accurate alignment, but lacks efficiency. The latter is fast, but often inaccurate. Here we document a new algorithm employing a technique known as quicksort. The results on both simulated data and real data show that this algorithm provides a dramatic increase in alignment speed and also improves alignment accuracy