Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer

Wnt-11 promotes cancer cell migration and invasion independently of β-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD8 is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-β signals to promote EMT. FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo. Analysis of patient samples reveals increased levels of FZD8 in cancer, correlating with Wnt-11. FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription. FZD8 silencing reduces prostate cancer cell migration, invasion, three-dimensional (3D) organotypic cell growth, expression of EMT-related genes, and TGF-β/Smad-dependent signaling. Mechanistically, FZD8 forms a TGF-β-regulated complex with TGF-β receptors that is mediated by the extracellular domains of FZD8 and TGFBR1. Targeting FZD8 may therefore inhibit aberrant activation of both Wnt and TGF-β signals in prostate cancer

The shallow water equations and their application to realistic cases

The numerical modelling of 2D shallow flows in complex geometries involving transient flow and movable boundaries has been a challenge for researchers in recent years. There is a wide range of physical situations of environmental interest, such as flow in open channels and rivers, tsunami and flood modelling, that can be mathematically represented by first-order non-linear systems of partial differential equations, whose derivation involves an assumption of the shallow water type. Shallow water models may include more sophisticated terms when applied to cases of not pure water floods, such as mud/debris floods, produced by landslides. Mud/debris floods are unsteady flow phenomena in which the flow changes rapidly, and the properties of the moving fluid mixture include stop and go mechanisms. The present work reports on a numerical model able to solve the 2D shallow water equations even including bed load transport over erodible bed in realistic situations involving transient flow and movable flow boundaries. The novelty is that it offers accurate and stable results in realistic problems since an appropriate discretization of the governing equations is performed. Furthermore, the present work is focused on the importance of the computational cost. Usually, the main drawback is the high computational effort required for obtaining accurate numerical solutions due to the high number of cells involved in realistic cases. However, the proposed model is able to reduce computer times by orders of magnitude making 2D applications competitive and practical for operational flood prediction. Moreover our results show that high performance code development can take advantage of general purpose and inexpensive Graphical Processing Units, allowing to run almost 100 times faster than old generation codes in some cases

Mechanical Properties Analysis of an Al-Mg Alloy Connecting Rod with Submicrometric Structure

AbstractIn spite of the fact that SPD processes considerably improve the mechanical properties of the thus processed materials, in a large number of cases, it is necessary the subsequent employment of a traditional manufacturing process, such as a forging process, in order to obtain the final shape of a specific part. Thus, in general, it is necessary to use a thermal treatment for the material before it is forged. In this research work, the measurement of the mechanical properties of an isothermally forged connecting rod is to carried out. The results obtained for an AA5754 aluminium alloy are to be compared in the case of two different starting states: after an annealing heat treatment and after having been previously ECAP deformed. It is observed an increase of 21% in the HV microhardness in relation to that attained in the connecting rod forged from the material without previous ECAP deformation

Microperimetry and Optical Coherence Tomography Changes in Type-1 Diabetes Mellitus without Retinopathy

Background: We aimed to measure and correlate inner retinal layer (IRL) thickness and macular sensitivity by optical coherence tomography (OCT) and by microperimetry, respectively, in type 1 diabetes mellitus patients (DM1) without diabetic retinopathy (DR). Methods: Fifty-one DM1 patients and 81 age-matched healthy subjects underwent measurement of the axial length (AL), retinal thickness in the macular ETDRS areas by swept source (SS)-OCT and macular sensitivity by microperimeter. Results: The total retinal and IRL thicknesses were thicker in the DM1 group (p < 0.05) in practically all ETDRS areas, and they had a generalized decrease in sensitivity (p < 0.05) in 9 areas between both groups. There was a significant negative correlation between retinal sensitivity and age in all areas and in visual acuity (VA) in 5 out of the 9 areas for DM1 patients. Only a mild negative correlation was observed between retinal sensitivity in the 5 degrees nasal inner (5NI) area and in IRL thickness in the temporal inner (TI) area (-0.309 with p = 0.029) in the DM1 group. Conclusion: Aging and disease evolution in DM1 patients without DR signs generate a decrease in retinal sensitivity. There was a direct relationship between retinal sensitivity and macular thickness in the DM1 group

Modification of corneal biomechanics and intraocular pressure following non-penetrating deep sclerectomy

Changes in the cornea can influence outcomes in patients with primary open-angle glaucoma (POAG). We aimed to evaluate the relevance of changes in corneal biomechanics and intraocular pressure (IOP) in patients undergoing non-penetrating deep sclerectomy (NPDS) with the Esnoper V2000 implant® (AJL Ophthalmic S.A., Gasteiz, Spain). We included 42 eyes of 42 patients with POAG scheduled for NPDS with the Esnoper V2000 implant. Biomechanical properties were measured by Ocular Response Analyzer® G3 (ORA; Reichert Inc., Depew, NY, USA). Corneal hysteresis (CH), corneal resistance factor (CRF), corneal compensated IOP (IOPcc), and Goldmann-correlated IOP (IOPg) were measured the day before surgery and on day 1, 7, and 30 and 2 and 3 months after surgery. CH initially increased, fell below the presurgical value at 30 days after the surgery, and increased again at 2 and 3 months. CRF, IOPcc, and IOPg decreased on the first day after surgery, then followed a trend of increasing but stayed below pre-surgery levels. All values reached statistical significance. While observed changes in corneal biomechanics after NPDS and Esnoper V2000 implant were significant, more studies are needed if we are to understand their influence on corneal biomechanics and their clinical relevance in POAG

Silver nanoparticles–polyethyleneimine-based coatings with antiviral activity against SARS-CoV-2: a new method to functionalize filtration media

The use of face masks and air purification systems has been key to curbing the transmission of SARS-CoV-2 aerosols in the context of the current COVID-19 pandemic. However, some masks or air conditioning filtration systems are designed to remove large airborne particles or bacteria from the air, being limited their effectiveness against SARS-CoV-2. Continuous research has been aimed at improving the performance of filter materials through nanotechnology. This article presents a new low-cost method based on electrostatic forces and coordination complex formation to generate antiviral coatings on filter materials using silver nanoparticles and polyethyleneimine. Initially, the AgNPs synthesis procedure was optimized until reaching a particle size of 6.2 ± 2.6 nm, promoting a fast ionic silver release due to its reduced size, obtaining a stable colloid over time and having reduced size polydispersity. The stability of the binding of the AgNPs to the fibers was corroborated using polypropylene, polyester-viscose, and polypropylene-glass spunbond mats as substrates, obtaining very low amounts of detached AgNPs in all cases. Under simulated operational conditions, a material loss less than 1% of nanostructured silver was measured. SEM micrographs demonstrated high silver distribution homogeneity on the polymer fibers. The antiviral coatings were tested against SARS-CoV-2, obtaining inactivation yields greater than 99.9%. We believe our results will be beneficial in the fight against the current COVID-19 pandemic and in controlling other infectious airborne pathogens. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

San Isidoro de León. Construcción y reconstrucción de una basílica románica

This paper shows the main results obtained thanks to the archaeological analysis of the standing walls of the basilica of San Isidoro de León, paying special attention to those affecting its conception and evolution during the 11th and 12th centuries. The research devoted to this building is characterised by a long debate regarding its buildings phases and the patronage of the monarchy of Leon. The analysis records an original basilica built in the mid 11th century. This construction is substituted by another one bigger in scale and with a transept, which suffers an immediate ruin that will mainly destroy the occidental area of the hall. The brick vaults and the Lamb’s Door sited in this part of the building belong thus to the restoration works carried out in the mid 12th century.Este artículo presenta los principales resultados obtenidos en el análisis arqueológico de los alzados de la basílica de San Isidoro de León, centrándose principalmente en aquellos que afectan a su concepción y evolución durante los siglos XI y XII. La extensa investigación que se ha ocupado de este edificio se caracteriza por un prolongado debate en torno a sus fases constructivas y al mecenazgo de la monarquía leonesa. El presente análisis constata una basílica originaria construida a mediados del siglo XI. Esta construcción será sustituida por otra de mayor escala y con transepto, la cual sufre una temprana ruina que afectará principalmente a la mitad occidental del aula. Tanto las bóvedas de ladrillo de esa zona como la Puerta del Cordero pertenecen a la obra de restauración de mediados del siglo XII

Con la dote de su mujer y el dinero de sus amigos. El ascenso económico y social de Francisco García de Huidobro, Marqués de Casa Real

Estudio de caso sobre Francisco García de Huidobro, tesorero establecedor de la Casa de Moneda de Santiago de Chile y primer marqués de Casa Real. Se describe su proceso de promoción económica y social en el contexto de reestructuración de la elite chilena de mediados del siglo XVIII, fundamentado inicialmente en el capital social proporcionado por su red de relaciones familiares y mercantiles. A partir del control de la acuñación, en apenas veinte años acumularía la principal fortuna de Chile, posicionándose sobre el resto de comerciantes santiaguinos y culminando su ascenso con la obtención de un título nobiliario

With his wife's dowry and his friend's money. The social and economic ascent of Francisco García de Huidobro, Marquis of Casa Real

Estudio de caso sobre Francisco García de Huidobro, tesorero establecedor de la Casa de Moneda de Santiago de Chile y primer marqués de Casa Real. Se describe su proceso de promoción económica y social en el contexto de reestructuración de la elite chilena de mediados del siglo XVIII, fundamentado inicialmente en el capital social proporcionado por su red de relaciones familiares y mercantiles. A partir del control de la acuñación, en apenas veinte años acumularía la principal fortuna de Chile, posicionándose sobre el resto de comerciantes santiaguinos y culminando su ascenso con la obtención de un título nobiliario.Case study about the figure of Francisco García de Huidobro, founding purser of the Mint of Santiago de Chile and first Marquis of Casa Real. The article describes his social and economic promotion in the context of the restructuration of Chilean elites in the mid-18th century. García de Huidobro ascent was made possible initially by the social capital provided by his social and mercantile network. Based on his control of the mint, in barely twenty years García de Huidobro managed to amass the largest fortune of Chile, rising above the rest of the Santiago merchant class and crowing this meteoric ascent with the award of a title of nobility

Structural and functional findings in patients with moderate diabetic retinopathy

Purpose: To evaluate structural and functional ocular changes in patients with type 2 diabetes mellitus (DM2) and moderate diabetic retinopathy (DR) without apparent diabetic macular edema (DME) assessed by optical coherence tomography (OCT) and microperimetry. Methods: This was a single-center cross-sectional descriptive study for which 75 healthy controls and 48 DM2 patients with moderate DR were included after applying exclusion criteria (one eye per patient was included). All eyes underwent a complete ophthalmic examination (axial length, macular imaging with swept-source OCT, and MAIA microperimetry). Macular thicknesses, ganglion cell complex (GCC) thicknesses, and central retinal sensitivity were compared between groups, and the relationships between the OCT and microperimetry parameters were evaluated. Results: Macular thickness was similar in both groups (242.17 ± 35.0 in the DM2 group vs 260.64 ± 73.9 in the control group). There was a diminution in the parafoveal area thickness in the DM2 group in the GCC complex. Retinal sensitivity was reduced in all sectors in the DM2 group. The central global value was 24.01 ± 5.7 in the DM2 group and 27.31 ± 2.7 in the control group (p < 0.001). Macular integrity was 80.89 ± 26.4 vs 64.70 ± 28.3 (p < 0.001) and total mean threshold was 23.90 ± 4.9 vs 26.48 ± 2.6 (p < 0.001) in the DM2 and control group, respectively. Moderate correlations were detected between the central sector of MAIA microperimetry and retina total central thickness (- 0.347; p = 0.0035). Age, visual acuity, and hemoglobin A1c levels also correlated with retinal sensitivity. Conclusion: Macular GCC thickness and central retinal sensitivity were reduced in patients with moderate DR without DME, suggesting the presence of macular neurodegeneration.[Figure not available: see fulltext.] © 2021, The Author(s)