Effect of high pressure homogenization and high power ultrasound on some physical properties of tomato juices with different concentration levels

The effect of high pressure homogenization (HPH) and ultrasound (US) on rheological properties, color, precipitate weight ratio, pectin esterification degree and cell integrity of tomato juices with different soluble solids content (5.0, 7.5, 10.0 Brix) was studied. Samples were subjected to HPH up to 150 MPa or US up to 30 min. The energy efficiency associated to the processes was also evaluated. Results showed that stress type and product concentration influenced the changes of tomato juice physical properties. In particular, HPH and US treatments were responsible for higher G0 and consistency of processed tomato juices than untreated samples. Increases in sample rheological properties were comparable for the 5.0 and 7.5 Brix treated HPH and US samples, whereas HPH was more effective than US in the case of 10.0 Brix sample. These changes were in agreement with other indexes, i.e. precipitate weight ratio increase and cell integrity decrease, and were attributed to stronger of inter-particle interactions. The process energy efficiency showed that lower energy was involved in HPH in comparison to US

Somatostatin Serves a Modulatory Role in the Mouse Olfactory Bulb: Neuroanatomical and Behavioral Evidence

Somatostatin (SOM) and somatostatin receptors (SSTR1–4) are present in all olfactory structures, including the olfactory bulb (OB), where SOM modulates physiological gamma rhythms and olfactory discrimination responses. In this work, histological, viral tracing and transgenic approaches were used to characterize SOM cellular targets in the murine OB. We demonstrate that SOM targets all levels of mitral dendritic processes in the OB with somatostatin receptor 2 (SSTR2) detected in the dendrites of previously uncharacterized mitral-like cells. We show that inhibitory interneurons of the glomerular layer (GL) express SSTR4 while SSTR3 is confined to the granule cell layer (GCL). Furthermore, SOM cells in the OB receive synaptic inputs from olfactory cortical afferents. Behavioral studies demonstrate that genetic deletion of SSTR4, SSTR2 or SOM differentially affects olfactory performance. SOM or SSTR4 deletion have no major effect on olfactory behavioral performances while SSTR2 deletion impacts olfactory detection and discrimination behaviors. Altogether, these results describe novel anatomical and behavioral contributions of SOM, SSTR2 and SSTR4 receptors in olfactory processing

Supporting central nervous system neuroprotection and remyelination by specific TLR4 antagonism

ApTOLL is an aptamer specifically designed to antagonize toll-like receptor 4 (TLR4), which is involved in the innate immunity that promotes inflammatory responses in several diseases, including multiple sclerosis (MS). MS is a chronic, immune, demyelinating and neurodegenerative disease of the central nervous system that represents the second most important cause of neurological disability in young adults. The drugs currently available to treat this disease are immunomodulators and, to date, there are no therapeutic remyelinating drugs available to manage MS. In this study, we show that TLR4 is located in post-mortem cortical lesions of MS patients and as a result, we evaluated the effect of its inhibition by ApTOLL in two different animal models of MS, that of experimental autoimmune encephalomyelitis (EAE) and the cuprizone model. ApTOLL administration ameliorated the clinical symptomatology of the affected mice, which was associated with better preservation and restoration of myelin and oligodendrocytes in the demyelinated lesions of these animals. This revealed not only an immunomodulatory but also a remyelinating effect of the treatment with ApTOLL which was corroborated on purified cultures of rodent and adult human oligodendrocyte precursor cells (OPCs). In summary, the molecular nature of ApTOLL and its mechanism of action strongly supports its further study and use in novel strategies to treat MS and eventually, other demyelinating diseases.This work was supported by grant IND2018/BMD-9751 (Programa de Doctorados Industriales, Comunidad de Madrid, Spain), SAF2016-77575-R (Spanish Ministerio de Economía, Industria y Competitividad-MINECO), and the contract for technological support ApTLR2019-PC-MS-001 (AptaTargets, S.L., Spain) to FdC. BF-G is currently hired by Aptatargets S.L., PG-M is hired under PEJ-2020-AI/BMD-18541 de la Comunidad de Madrid, Spain (associated with the youth guarantee fund to FdC), SN had a predoctoral contract from the UCLM and was hired under SAF2012-40023, SAF2016- 77575-R, RD12-0032/0012 and RD16-0015/0019 (Spanish Ministerio de Economía, Industria y Competitividad-MINECO) and IND2018/BMD-9751, YL has been contracted under ReTics and SAF (to FdC). We thank David Segarra and Mª Eugenia Zarabozo (AptaTargets S.L.) for their constant technological support, Laude Garmendia for her indispensable constant help at the animal facility (Instituto Cajal-CSIC), including the extra effort during Covid-19 pandemics, Profs María Ángeles Moro (Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid and Universidad Complutense de Madrid, Spain) and Ignacio Lizasoaín (Universidad Complutense de Madrid, Spain) for lending us the TLR4 knockout mice, and the former GNDe member Dr. Carolina MeleroJerez (currently working at JazzPharma, Spain) for the initial training of BF-G on EAE animal model and different techniques at the laboratory. Human samples were supplied by the UK Multiple Sclerosis Tissue Bank, funded by the Multiple Sclerosis Society of Great Britain and Northern Ireland (registered charity 207495).N

Proyecto Puentes: conectando la universidad con la salud mental comunitaria

Se presenta la memoria del Proyecto Puentes, cuya finalidad es explorar e implementar vías de participación entre la comunidad universitaria y las personas con problemas de salud mental. Es decir, tender puentes entre lo académico y la realidad de esas personas, con el propósito de conseguir una fuente de aprendizaje significativo para el estudiantado de la UCM, pero también herramientas útiles en los procesos de recuperación e integración de las personas con problemáticas de salud mental.Depto. de Personalidad, Evaluación y Psicología ClínicaFac. de PsicologíaFALSEsubmitte

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Genetic approach to study the role of Sonic Hedgehog in physiological CNS myelination and remyelination

La vía de señalización de Hedgehog es determinante en la regulación de la organogénesis en los vertebrados y juega un papel clave en la organización del SNC. De todos los miembros de la familia, Sonic Hedgehog (Shh) es el ligando mejor estudiado. Durante el desarrollo, Shh actúa como morfógeno secretable, dando lugar a gradientes de concentración. En el cerebro adulto, Shh continúa activo, modulando la autorrenovación y la especificación de las células madre neurales (NSC). Además, la señalización de Hedgehog se sobre expresa después de una lesión cerebral aguda. Estudios recientes han demostrado que los progenitores de la zona subventricular ventral (V-SVZ) postnatal del prosencéfalo dorsal requieren señalización Shh para dar lugar a nuevos oligodendrocitos (OL) en el cuerpo calloso (CC). Los OL son células gliales que mielinizan los axones y desempeñan un papel fundamental en el desarrollo y correcta transmisión de los impulsos nervioso. Existe una población sustancial de células precursoras de oligodendrocitos (OPC) que permanece quiescente pero activable durante en el SNC adulto: estos OPCs son necesarias para mantener la plasticidad y el mantenimiento de la mielina, así como después episodios de desmielinización como los que ocurren durante la esclerosis múltiple (EM). Una de las moléculas que se sobre-expresan en las lesiones desmielinizantes que caracterizan a esta enfermedad es Shh lo que, potencialmente, regula las respuestas de los OPC y el proceso de remielinización espontánea postlesión. Sin embargo, el efecto directo de la señalización de Shh sobre los OPCs durante el desarrollo posnatal y en respuesta a la desmielinización siguen siendo importantes cuestiones abiertas. La presente tesis doctoral estudia cómo la sobre-expresion y la inhibición parcial de la vía de Shh afecta la diferenciación de los OPC tanto durante la mielinización postnatal, como durante los fenómenos de desmielinización y remielinización del CC del cerebro adulto. Al trasplantar OPCs en zonas del SNC que no presentan mielina en condiciones fisiológicas, como la retina, se demuestra que el efecto de la activación/inhibición de esta cascada es dependiente de factores ambientales que difieren en función del estadio de desarrollo. Finalmente, estudiamos por primera vez el efecto directo del ligando Shh sobre OPCs aislados de corteza cerebral de humano adulto

Localization and physiological role of somatostatin receptor 4 (sst4) in the olfactory bulb: new insights from sst4-ko mice

The olfactory bulb (OB) is the first central relay of the olfactory sense. Through its laminar organization with well-defined cytoarchitecture and physiology, it mediates perception and integration of the olfactory signals. Sensory neuron axons synapse directly onto the apical dendrites of its principal neurons, the mitral and tufted cells, which the relay the olfactory information directly toward the olfactory cortex and other brain regions. As in most sensory system, synaptic transmission is finely tuned by GABAergic inhibitory interneurons which process the incoming information at different levels of the neural network. The main bulbar interneuron populations, known to process the olfactory inputs, are the periglomerular and granule cells. But based on their morphology, localization and neurochemical properties, various interneurons sub-populations coexist whose specific roles in the synaptic and cellular plasticity of the bulbar network are extensively studied. Among them, some interneurons express neuropeptides. More than just neurochemical markers, neuropeptides are known to act as important regulators of neurochemical activity, able to regulate neuronal excitability of neural networks. Somatostatin (SRIF) is one of the most abundant neuropeptide in the adult central nervous system (CNS). Six G-protein-coupled receptors, sst1, sst2A, sst2B, sst3, sst4, and sst5 mediate their cellular actions. SRIF is found in the mammalian OB, with immunoreactive cells and fibers found in the inner granule cell and external plexiform layers and to a lesser extent in the pe-ripheral glomerular layer. Binding and immunohistochemical data evidenced a differential distribution of sst2, sst3 and sst4 receptors through the bulbar layers, suggesting that the peptide modulates distinct levels of olfactory processing from information processing to integration or memorization of the olfactory signals (see Martel et al, 2014 in appendix). The aim of this work was to decipher the functional role of the sst4 receptor in the physiology of the OB. Based on preliminary 125-SRIF binding results showing a prominent sst4-type labeling in the glomerular layer, I focused on glomerular neurons. Immuno-histochemical studies performed on coronal sections of mouse OB shown that sst4 receptors are restricted to a calretinin-positive subpopulation of TH-negative GABAergic interneurons in the GL . On the other side a behavioral study was performed to investigate the functional consequences of sst4 invalidation on olfactory performances. Wild-type and sst4 KO male mice were compared in a battery of behavioral protocols aimed at detecting olfactory acuity, discrimination or memory defects, using spontaneous odor exploration and discrimination tasks and olfactory operant conditioning in an automated olfactometer. However, no major olfactory defect was observed in sst4-invalidated mice during the behavioral screening

GENETIC APPROACH TO STUDY THE ROLE OF SONIC HEDGEHOG IN PHYSIOLOGICAL CNS MYELINATION AND REMYELINATION

Tesis leída en la Universidad de Castilla-La Mancha ( España ) en 2021La vía de señalización de Hedgehog es determinante en la regulación de la organo-génesis en los vertebrados y juega un papel clave en la organización del SNC. De to-dos los miembros de la familia, Sonic Hedgehog (Shh) es el ligando mejor estudiado. Durante el desarrollo, Shh actúa como morfógeno secretable, dando lugar a gradien-tes de concentración. En el cerebro adulto, Shh continúa activo, modulando la auto-rrenovación y la especificación de las células madre neurales (NSC). Además, la se-ñalización de Hedgehog se sobre-expresa después de una lesión cerebral aguda. Es-tudios recientes han demostrado que los progenitores de la zona subventricular ven-tral (V-SVZ) postnatal del prosencéfalo dorsal requieren señalización Shh para dar luegar a nuevos oligodendrocitos (OL) en el cuerpo calloso (CC). Los OL son células gliales que mielinizan los axones y desempeñan un papel fundamental en el desa-rrollo y correcta transmisión de los impulsos nervioso. Existe una población sustan-cial de células precursoras de oligodendrocitos (OPC) que permanece quiescente pe-ro activable durante en el SNC adulto: estos OPCs son necesarias para mantener la plasticidad y el mantenimiento de la mielina, así como después episodios de desmie-linización como los que ocurren durante la esclerosis múltiple (EM). Una de las mo-léculas que se sobre-expresan en las lesiones desmielinizantes que caracterizan a es-ta enfermedad es Shh lo que, potencialmente, regula las respuestas de los OPC y el proceso de remielinización espontánea postlesión. Sin embargo, el efecto directo de la señalización de Shh sobre los OPCs durante el desarrollo posnatal y en respuesta a la desmielinización siguen siendo importantes cuestiones abiertas. La presente tesis doctoral estudia cómo la sobre-expresion y la inhibición parcial de la vía de Shh afec-ta la diferenciación de los OPC tanto durante la mielinización postnatal, como duran-te los fenómenos de desmielinización y remielinización del CC del cerebro adulto. Al trasplantar OPCs en zonas del SNC que no presentan mielina en condiciones fisioló-gicas, como la retina, se demuestra que el efecto de la activación/inhibición de esta cascada es dependiente de factores ambientales que difieren en función de el esta-dio de desarrollo. Finalmente, estudiamos por primera vez el efecto directo del li-gando Shh sobre OPCs aislados de corteza cerebral de humano adulto

Study on high pressure homogenization and high power ultrasound effectiveness in inhibiting polyphenoloxidase activity in apple juice

High pressure homogenization (HPH) and ultrasound with (USct) or without (US) temperature control were applied to apple juice individually or in combination for inactivating polyphenoloxidase (PPO). Ten passes HPH at 150 MPa were needed to achieve 50% PPO inactivation. USct led to 90% PPO decrease at the longest time (45 min), whereas total enzyme inactivation was achieved by subjecting samples to 6 min US. Results showed that temperature affected enzyme inactivation rather than the process applied. Moreover, the HPH-USct and HPH-US combined treatments led to enzyme residual activities similar to those caused by the application of HPH and USct, and US individual treatments, respectively. US provided to the apple juice less energy density to obtain PPO inactivation than USct and HPH, due to the contribution of the in situ generated heat. Also, US showed the lowest energy consumption, thus confirming its appropriateness

La recherche orientée par la conception, une voie pour soutenir le développement professionnel des conseillers pédagogiques : le cas du projet TOPIC

International audienceDe plus en plus d'établissements d'enseignement supérieur disposent d'équipements de visioconférence et de téléprésence immersive permettant de donner le sentiment aux utilisateurs d'être présents autour d'une même table de manière synchrone, et ce grâce à une grande qualité sonore et visuelle. Ces équipements ne sont toutefois pas adaptés aux besoins de l'enseignement et les enseignants, les conseillers pédagogiques et les chercheurs ont besoin de clés de compréhension permettant de faire évoluer leurs dispositifs de formation (Lameul et Loisy, 2014). Dans ce cadre, il est crucial de bâtir un répertoire de connaissances rigoureuses et critiques autour des approches pédagogiques adaptées, des effets de ces dispositifs sur l'apprentissage des étudiants (Albero, 2011) ou encore des innovations pédagogiques émergentes (Bédard et Béchard, 2009).Pour ce faire, nous menons un projet de recherche orientée par la conception (Sanchez et Monod-Ansaldi, 2015) intitulé TOPIC (Téléprésence comme OPportunité d'Innovation dans la Conception en contexte de formation). Misant sur une collaboration étroite entre chercheurs et formateurs, TOPIC vise l'élaboration de formations à l'usage pédagogique de ces équipements s'appuyant la recherche. Il vise aussi une contribution au développement de connaissances nouvelles dans ce domaine. Nous questionnerons dans quelle mesure une telle recherche représente une voie pour soutenir le développement professionnel des conseillers pédagogiques.