Determination of lactadherin concentration in dairy by-products by ELISA: Effect of heat treatment and hydrolysis

Lactadherin is a peripheral glycoprotein of the milk fat globule membrane with several attributed biological activities. In this study, we developed an indirect competitive ELISA to determine lactadherin concentration by using a rabbit polyclonal antiserum. The ELISA was applied to quantify lactadherin in several dairy by-products. Of the products tested, raw and commercial buttermilk had the highest concentrations of lactadherin (6.79 and 5.27 mg/g of product, respectively), followed by commercial butter serum (4.86 mg/g), commercial skim milk (4.84 mg/g), and raw whey (1.20 mg/g). The concentration of immunoreactive lactadherin was also determined in dairy by- products after they were subjected to different technological treatments. Thus, raw products were heat treated at combinations of temperature and time typically used in the dairy industry, and commercial products were hydrolyzed using 3 proteolytic enzyme preparations. Heat treatments of whey and buttermilk resulted in a smaller decrease in lactadherin concentration than did hydrolysis as determined by ELISA and electrophoresis. At high temperatures for long durations, the loss of lactadherin was higher in whey than in buttermilk, with the maximal reduction of around 48% found after treating whey at 72 degrees C for 60 min. Hydrolysis of commercial products with proteolytic enzymes resulted in a marked decrease of immunoreactivity within the first 5 min of treatment, which thereafter was constant throughout 4 h of hydrolysis. These results demonstrate that dairy by- products from milk fat processing are good natural sources of lactadherin, although technological processes have to be considered, because they have different effects on lactadherin content

Synthesis and ex vivo biodistribution of two 68Ga-labeled tetrazine tracers : comparison of pharmacokinetics

Peer reviewe

Paradoxical effects of JZL184, an inhibitor of monoacylglycerol lipase, on bone remodelling in healthy and cancer-bearing mice

Background Cancer-associated bone disease is a serious complication in bone sarcomas and metastatic carcinomas of breast and prostate origin. Monoacylglycerol lipase (MAGL) is an enzyme of the endocannabinoid system, and is responsible for the degradation of the most abundant endocannabinoid in bone, 2-arachidonoyl glycerol (2AG). Methods The effects of the verified MAGL inhibitor on bone remodelling were assessed in healthy mice and in mouse models of bone disease caused by prostate and breast cancers and osteosarcoma. Findings JZL184 reduced osteolytic bone metastasis in mouse models of breast and prostate cancers, and inhibited skeletal tumour growth, metastasis and the formation of ectopic bone in models of osteosarcoma. Additionally, JZL184 suppressed cachexia and prolonged survival in mice injected with metastatic osteosarcoma and osteotropic cancer cells. Functional and histological analysis revealed that the osteoprotective action of JZL184 in cancer models is predominately due to inhibition of tumour growth and metastasis. In the absence of cancer, however, exposure to JZL184 exerts a paradoxical reduction of bone volume via an effect that is mediated by both Cnr1 and Cnr2 cannabinoid receptors. Interpretation MAGL inhibitors such as JZL184, or its novel analogues, may be of value in the treatment of bone disease caused by primary bone cancer and bone metastasis, however, activation of the skeletal endocannabinoid system may limit their usefulness as osteoprotective agents

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

Trivial-to-Learn: Aprendizaje basado en juegos en el área de conocimiento de Farmacia y Tecnología Farmacéutica (TRIVIALFAR)

La sociedad actual demanda a las Instituciones Educativas profesionales que tengan una formación integral que les permita adaptarse al entorno y a los requerimientos sociolaborales. Para ello, es esencial el empleo de metodologías docentes activas, como el aprendizaje basado en juegos, donde el estudiante es el protagonista del proceso de enseñanza-aprendizaje. El objetivo principal de este proyecto es diseñar y desarrollar juegos tipo Trivial como estrategia de aprendizaje activo en las asignaturas del área de conocimiento de Farmacia y Tecnología Farmacéutica. Concretamente se han desarrollado dos tipos de actividades: juegos tipo Trivial virtuales en la asignatura de Biofarmacia y Farmacocinética, y juegos tipo Trivial presenciales en las asignaturas de Productos Sanitarios y Tecnología Farmacéutica I. Ambas actividades han resultado ser una excelente herramienta de autoevaluación y repaso de los contenidos impartidos en la asignatura. Los juegos desarrollados en modalidad presencial fueron mejor evaluados por los alumnos que los desarrollados en modalidad virtual. Además, estos juegos presenciales les permitía adquirir competencias transversales, principalmente habilidades comunicativas, de liderazgo y de trabajo colaborativo.Depto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaFALSEsubmitte

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F

Nested inversion polymorphisms predispose chromosome 22q11.2 to meiotic rearrangements [RETRACTED]

Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders