The role of autophagy in liver epithelial cells and its Impact on systemic homeostasis

Autophagy plays a role in several physiological and pathological processes as it controls the turnover rate of cellular components and influences cellular homeostasis. The liver plays a central role in controlling organisms’ metabolism, regulating glucose storage, plasma proteins and bile synthesis and the removal of toxic substances. Liver functions are particularly sensitive to autophagy modulation. In this review we summarize studies investigating how autophagy influences the hepatic metabolism, focusing on fat accumulation and lipids turnover. We also describe how autophagy affects bile production and the scavenger function within the complex homeostasis of the liver. We underline the role of hepatic autophagy in counteracting the metabolic syndrome and the associated cardiovascular risk. Finally, we highlight recent reports demonstrating how the autophagy occurring within the liver may affect skeletal muscle homeostasis as well as different extrahepatic solid tumors, such as melanoma

Roe deer summer habitat selection at multiple spatio-temporal scales in an Alpine environment

Habitat selection is a hierarchical process that may involve different patterns depending on the spatial and temporal scales of investigation. We studied habitat selection by European roe deer (Capreolus capreolus) in a very diverse environment in the Italian eastern Alps, during summer. We sampled both coarse-grained habitat variables (topographic variables, habitat types and cover) and fine-grained habitat variables (forage components of habitat) in used and available locations along the movement trajectories of 14 adult roe deer equipped with GPS telemetry collars. We used conventional logistic regression to assess roe deer habitat selection at the seasonal home range scale, and conditional logistic regression to take into account the temporal aspect of habitat selection on a weekly basis. Our results indicate that topographic variables were not significant predictors for summer roe deer habitat selection. Roe deer strongly selected dense canopy cover, probably to avoid heat stress during warm summer days. In accordance with previous observations, roe deer preferred young forest stands dominated by pioneer species such as ash (Fraxinus spp.) and hazel (Corylus avellana) over climax environments. Roe deer positively selected shrubs (in particular Fraxinus spp., Erica herbacea, Rhododendron spp. and Vaccinium spp.) throughout the study period, whereas selection for grasses and sedges emerged only at the weekly scale. Habitat selection was clearly related to vegetation phenology, since roe deer selected plants in the most nutritive phenological stages, i.e., shrubs with buds, new leaves and fruits, and newly emergent grasses and sedges. Finally, we found stronger and more significant regression coefficients for forage components of habitat and habitat types at the weekly scale, indicating that matching spatial and temporal scales may improve our understanding of ecological patterns driving habitat selection. Conversely, selection patterns for canopy cover did not change across scales, indicating that this variable likely drives habitat selection in a similar way throughout the entire season

Roe deer summer habitat selection at multiple spatio-temporal scales in an alpine environment

Habitat selection is a hierarchical process that may involve different patterns depending on the spatial and temporal scales of investigation. We studied habitat selection by European roe deer (Capreolus capreolus) in a very diverse environment in the Italian eastern Alps, during summer. We sampled both coarse-grained habitat variables (topographic variables, habitat types and cover) and fine-grained habitat variables (forage components of habitat) in used and available locations along the movement trajectories of 14 adult roe deer equipped with GPS telemetry collars. We used conventional logistic regression to assess roe deer habitat selection at the seasonal home range scale, and conditional logistic regression to take into account the temporal aspect of habitat selection on a weekly basis. Our results indicate that topographic variables were not significant predictors for summer roe deer habitat selection. Roe deer strongly selected dense canopy cover, probably to avoid heat stress during warm summer days. In accordance with previous observations, roe deer preferred young forest stands dominated by pioneer species such as ash (Fraxinus spp.) and hazel (Corylus avellana) over climax environments. Roe deer positively selected shrubs (in particular Fraxinus spp., Erica herbacea, Rhododendron spp. and Vaccinium spp.) throughout the study period, whereas selection for grasses and sedges emerged only at the weekly scale. Habitat selection was clearly related to vegetation phenology, since roe deer selected plants in the most nutritive phenological stages, i.e., shrubs with buds, new leaves and fruits, and newly emergent grasses and sedges. Finally, we found stronger and more significant regression coefficients for forage components of habitat and habitat types at the weekly scale, indicating that matching spatial and temporal scales may improve our understanding of ecological patterns driving habitat selection. Conversely, selection patterns for canopy cover did not change across scales, indicating that this variable likely drives habitat selection in a similar way throughout the entire season

Abnormal salivary total and oligomeric alpha-synuclein in Parkinson's disease

In Parkinson’s disease (PD), alpha-synuclein (a-syn) can be detected in biological fluids including saliva. Although previous studies found reduced a-syn total (a-syntotal) concentration in saliva of PD patients, no studies have previously examined salivary a-syn oligomers (a-synolig) concentrations or assessed the correlation between salivary a-syntotal, a-synolig and clinical features in a large cohort of PD patients. Is well known that a-synolig exerts a crucial neurotoxic effect in PD. We collected salivary samples from 60 PD patients and 40 age- and sex-comparable healthy subjects. PD was diagnosed according to the United Kingdom Brain Bank Criteria. Samples of saliva were analyzed by specific anti-a-syn and anti-oligomeric a-syn ELISA kits. A complete clinical evaluation of each patient was performed using MDS-Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, Montreal Cognitive Assessment and Frontal Assessment Battery. Salivary a-syntotal was lower, whereas a-synolig was higher in PD patients than healthy subjects. The a-synolig/a-syntotal ratio was also higher in patients than in healthy subjects. Salivary a-syntotal concentration negatively correlated with that of a-synolig and correlated with several patients’ clinical features. In PD, decreased salivary concentration of a-syntotal may reflect the reduction of a-syn monomers (a-synmon), as well as the formation of insoluble intracellular inclusions and soluble oligomers. The combined detection of a-syntotal and a-synolig in the saliva might help the early diagnosis of P

Experimental and Numerical Analysis of the Hydrodynamics around a Vertical Cylinder in Waves

The present study provides an extensive analysis on the hydrodynamics induced by a vertical slender pile under wave action. The authors carried out the study both experimentally and numerically, thus enabling a deep understanding of the flow physics. The experiments took place at a wave flume of the Universita Politecnica delle Marche. Two different experimental campaigns were performed: In the former one, a mobile bed model was realized with the aims to study both the scour process and the hydrodynamics around the cylinder; in the latter one, the seabed was rigid in order to make undisturbed optical measurements, providing a deeper analysis of the hydrodynamics. The numerical investigation was made by performing a direct numerical simulation. A second order numerical discretization, both in time and in space, was used to solve the Navier-Stokes equations while a volume of fluid (VOF) approach was adopted for tracking the free surface. The comparison between experimental and numerical results is provided in terms of velocity, pressure distributions around the cylinder, and total force on it. The analysis of the pressure gradient was used to evaluate the generation and evolution of vortices around the cylinder. Finally, the relation between scour and bed shear stresses due to the structure of the vortex pattern around the pile was assessed. It is worth noting that the physical understanding of this last analysis was enabled by the combined use of experimental data on scour and numerical data on the flow pattern

Myomir dysregulation and reactive oxygen species in aged human satellite cells

AbstractSatellite cells that reside on the myofibre surface are crucial for the muscle homeostasis and regeneration. Aging goes along with a less effective regeneration of skeletal muscle tissue mainly due to the decreased myogenic capability of satellite cells. This phenomenon impedes proper maintenance and contributes to the age-associated decline in muscle mass, known as sarcopenia. The myogenic potential impairment does not depend on a reduced myogenic cell number, but mainly on their difficulty to complete a differentiation program. The unbalanced production of reactive oxygen species in elderly people could be responsible for skeletal muscle impairments. microRNAs are conserved post-transcriptional regulators implicated in numerous biological processes including adult myogenesis. Here, we measure the ROS level and analyze myomiR (miR-1, miR-133b and miR-206) expression in human myogenic precursors obtained from Vastus lateralis of elderly and young subjects to provide the molecular signature responsible for the differentiation impairment of elderly activated satellite cells

Distinct serum and cerebrospinal fluid cytokine and chemokine profiles in autoantibody-associated demyelinating diseases

Background: Demyelinating diseases of the central nervous system associated with autoantibodies against aquaporin-4 and myelin-oligodendrocyte-glycoprotein are mediated by different immunopathological mechanisms compared to multiple sclerosis. Objective: The purpose of this study was to evaluate serum and cerebrospinal fluid cytokine/chemokine profiles in patients with autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein-associated demyelination compared to multiple sclerosis and autoimmune encephalitis. Methods: Serum and cerebrospinal fluid cytokine/chemokine levels were analysed using Procartaplex Multiplex Immunoassays. First, we analysed a panel of 32 cytokines/chemokines in a discovery group (nine aquaporin-4-antibody seropositive, nine myelin oligodendrocyte glycoprotein-antibody seropositive, eight encephalitis, 10 multiple sclerosis). Significantly dysregulated cytokines/chemokines were validated in a second cohort (11 aquaporin-4-antibody seropositive, 18 myelin oligodendrocyte glycoprotein-antibody seropositive, 18 encephalitis, 33 multiple sclerosis). Results: We found 11 significantly altered cytokines/chemokines in cerebrospinal fluid and serum samples in the discovery group (a proliferation-inducing ligand, fractalkine=CX3CL1, growth-regulated oncogene-\u3b1, interleukin-1 receptor antagonist, interleukin-6, interleukin-8=CXCL8, interleukin-10, interleukin-21, interferon-&3-induced protein-10=CXCL10, monokine induced by interferon-&3=CXCL9, macrophage inflammatory protein-1 f=CCL4). Most of these cytokines/chemokines were up-regulated in autoantibodies against aquaporin-4 or autoantibodies against myelin-oligodendrocyte-glycoprotein positive patients compared to multiple sclerosis. We confirmed these results for cerebrospinal fluid interleukin-6 and serum interleukin-8, growth-regulated oncogene-\u3b1, a proliferation-inducing ligand and macrophage inflammatory protein-1\u3b2 in the validation set. Receiver-operating characteristic analysis revealed increased levels of cerebrospinal fluid interleukin-6, serum interleukin-8 and growth-regulated oncogene-\u3b1 in most patients with autoantibody-associated neurological diseases. Conclusion: This study suggests that distinctive cerebrospinal fluid and serum cytokine/chemokine profiles are associated with autoantibody-mediated demyelination, but not with multiple sclerosis

Interculturalidad y educación desde el sur: Contextos, experiencias y voces

Interculturalidad y educación desde el Sur. Contextos, experiencias y voces es un libro colectivo que corona once trabajos de investigación realizados por diecisiete autores con diferentes adscripciones institucionales que se articulan a través de grupos de trabajo latinoamericanos en torno al debate actual sobre la Interculturalidad y Educación. Y con ello obligan al lector a pensar simultáneamente en un conjunto de movimientos o desplazamientos teórico-conceptuales, en el despliegue de posicionamientos éticos, filosóficos, políticos y jurídicos, y en el desarrollo de metodologías de investigación novedosas, que nos posibiliten revelar y actuar sobre una diversidad de experiencias, modelos y programas que buscan potenciar los procesos interculturales en el Sur. La obra en su conjunto es un aporte a la creciente producción bibliográfica que se genera en la última década desde la perspectiva crítica de Latinoamérica

Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder

A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD)

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists