Bar-driven evolution and quenching of spiral galaxies in cosmological simulations

We analyse the output of the hi-res cosmological zoom-in simulation ErisBH to study self-consistently the formation of a strong stellar bar in a Milky Way-type galaxy and its effect on the galactic structure, on the central gas distribution and on star formation. The simulation includes radiative cooling, star formation, SN feedback and a central massive black hole which is undergoing gas accretion and is heating the surroundings via thermal AGN feedback. A large central region in the ErisBH disk becomes bar-unstable after z~1.4, but a clear bar-like structure starts to grow significantly only after z~0.4, possibly triggered by the interaction with a massive satellite. At z~0.1 the bar reaches its maximum radial extent of l~2.2 kpc. As the bar grows, it becomes prone to buckling instability, which we quantify based on the anisotropy of the stellar velocity dispersion. The actual buckling event is observable at z~0.1, resulting in the formation of a boxy-peanut bulge clearly discernible in the edge-on view of the galaxy at z=0. The bar in ErisBH does not dissolve during the formation of the bulge but remains strongly non-axisymmetric down to the resolution limit of ~100 pc at z=0. During its early growth, the bar exerts a strong torque on the gas within its extent and drives gas inflows that enhance the nuclear star formation on sub-kpc scales. Later on the infalling gas is nearly all consumed into stars and, to a lesser extent, accreted onto the central black hole, leaving behind a gas-depleted region within the central ~2 kpc. Observations would more likely identify a prominent, large-scale bar at the stage when the galactic central region has already been quenched. Bar-driven quenching may play an important role in disk-dominated galaxies at all redshift. [Abridged]Comment: 13 pages, 12 figures, MNRAS submitte

Neuronal (Bi)Polarity as a Self-Organized Process Enhanced by Growing Membrane

Early in vitro and recent in vivo studies demonstrated that neuronal polarization occurs by the sequential formation of two oppositely located neurites. This early bipolar phenotype is of crucial relevance in brain organization, determining neuronal migration and brain layering. It is currently considered that the place of formation of the first neurite is dictated by extrinsic cues, through the induction of localized changes in membrane and cytoskeleton dynamics leading to deformation of the cells' curvature followed by the growth of a cylindrical extension (neurite). It is unknown if the appearance of the second neurite at the opposite pole, thus the formation of a bipolar cell axis and capacity to undergo migration, is defined by the growth at the first place, therefore intrinsic, or requires external determinants. We addressed this question by using a mathematical model based on the induction of dynamic changes in one pole of a round cell. The model anticipates that a second area of growth can spontaneously form at the opposite pole. Hence, through mathematical modeling we prove that neuronal bipolar axis of growth can be due to an intrinsic mechanism

Isolation and Cryopreservation of Animal Mesenchymal Stromal Cells

Scientific progress in cellular and molecular biotechnology has led to the development of advanced therapies, such as gene therapy, cell therapy, and tissue engineering. The application of stem cells as therapeutic agents has been investigated for several years in human medicine and, more recently, the same approach has been considered in the veterinary field as a novel opportunity for the treatment of animal diseases. Mesenchymal stem cell (MSC)-based therapies seem to contribute to the healing process by several mechanisms due to their peculiar biological features. It has been shown that MSCs could effectively differentiate into the required cell type to replace the damaged tissue. Furthermore, due to their autocrine and paracrine secretory activities, these cells are a powerful source of trophic mediators, growth factors, cytokines, and extracellular matrix components. The clinical application of MSCs needs great amounts of cells designed for in vivo implantation that can be obtained following their in vitro isolation, serial subcultivations, cryopreservation, and thawing. These procedures could determine their feature changes which could interfere with the therapeutic outcome. For these reasons, to preserve MSCs after in vitro manipulation for future applications, standardized quality controls and a reliable long-term cryopreservation method are required

Health monitoring program for the control of laboratory animal diseases

Pathogens present in the environment are the biggest source of diseases and epidemics in the breeding of laboratory animals. In fact, the presence of microorganisms can critically influence the animal health status and, consequently, the validity and reproducibility of experimental data. In accordance with the 3Rs principle (Refinement, Reduction, Replacement), this study is part of the Refinement concept. The FELASA guidelines, formulated with the aim of guaranteeing the best animal health state, are a valid support for researchers. In this preliminary study, health-monitoring program was carried out within the breeding of laboratory animals in IZSLER facility. The main murine viruses were analyzed through molecular biology techniques (PCR, RT-PCR) and enzyme immunoassays (indirect ELISA). The established surveillance program steadily guarantees animal health and ensures the most controlled environmental and sanitary conditions. Further investigations will be needed to develop virus control strategies

Application of two in vitro methods for the toxicity test of autogenous vaccines

According to the 3Rs principle (Replacement, Refinement, Reduction), this study aims to find alternative methods to evaluate the toxicity of autogenous vaccines. Currently in Italy the Istituti Zooprofilattici Sperimentali (II.ZZ.SS.) must perform the in vivo toxicity test for each lot of autogenous vaccine produced as laid down in the Decree of 17 March 1994. This paper describes two in vitro methods for assessing the toxicity of autogenous vaccines. The first is the MTT test based on the metabolic reaction of tetrazolium salt in vital cells. The second method is the test for measurement of IL-1ß production by macrophages, obtained after in vitro differentiation from pig monocytes in peripheral blood mononuclear cells. The two tests were performed on different vaccine antigens dilution: 1:20, 1:100 and 1:500. The results show a positive tendency between the two methods pointing out the potential of these methodologies combined for the replacement of the current in vivo test

Hep3Gel: A Shape-Shifting Extracellular Matrix-Based, Three-Dimensional Liver Model Adaptable to Different Culture Systems

Drug-induced hepatotoxicity is a leading cause of clinical trial withdrawal. Therefore, in vitro modeling the hepatic behavior and functionalities is not only crucial to better understand physiological and pathological processes but also to support drug development with reliable high-throughput platforms. Different physiological and pathological models are currently under development and are commonly implemented both within platforms for standard 2D cultures and within tailor-made chambers. This paper introduces Hep3Gel: a hybrid alginate-extracellular matrix (ECM) hydrogel to produce 3D in vitro models of the liver, aiming to reproduce the hepatic chemomechanical niche, with the possibility of adapting its shape to different manufacturing techniques. The ECM, extracted and powdered from porcine livers by a specifically set-up procedure, preserved its crucial biological macromolecules and was embedded within alginate hydrogels prior to crosslinking. The viscoelastic behavior of Hep3Gel was tuned, reproducing the properties of a physiological organ, according to the available knowledge about hepatic biomechanics. By finely tuning the crosslinking kinetics of Hep3Gel, its dualistic nature can be exploited either by self-spreading or adapting its shape to different culture supports or retaining the imposed fiber shape during an extrusion-based 3D-bioprinting process, thus being a shape-shifter hydrogel. The self-spreading ability of Hep3Gel was characterized by combining empirical and numerical procedures, while its use as a bioink was experimentally characterized through rheological a priori printability evaluations and 3D printing tests. The effect of the addition of the ECM was evident after 4 days, doubling the survival rate of cells embedded within control hydrogels. This study represents a proof of concept of the applicability of Hep3Gel as a tool to develop 3D in vitro models of the liver

Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents

Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation. Given that Akt de-phosphorylation is required for glutamate receptor internalization and LTD, we hypothesized that the decrease in cholesterol in neuronal membranes may contribute to the deficits in LTD typical of aging. Here, we show that cholesterol loss triggers p-Akt accumulation, which in turn perturbs the normal cellular and molecular responses induced by LTD, such as impaired AMPA receptor internalization and its reduced lateral diffusion. Electrophysiology recordings in brain slices of old mice and in anesthetized elderly rats demonstrate that the reduced hippocampal LTD associated with age can be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.publishedVersionFil: Martín, Mauricio Gerardo. Consejo Superior de Investigaciones Científicas. Centro de Biología Molecular Severo Ochoa; España.Fil: Martín, Mauricio Gerardo. Universidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa; España.Fil: Martín, Mauricio Gerardo. Katholieke Universiteit Leuven. Center for Human Genetics. VIB Center for the Biology of Disease; Bélgica.Fil: Ahmed, Tariq. Katholieke Universiteit Leuven. Faculty of Psychology and Educational Sciences. Laboratory of Biological Psychology; Bélgica.Fil: Korovaichuk, Alejandra. Consejo Superior de Investigaciones Científicas. Instituto Cajal. Departamento de Neurobiología Funcional y de Sistemas; España.Fil: Venero, César. Universidad Nacional de Educación a Distancia. Facultad de Psicología. Departamento de Psicobiología; España.Fil: Menchón, Silvia Adriana. Katholieke Universiteit Leuven. Center for Human Genetics. VIB Center for the Biology of Disease; Bélgica.Fil: Menchón, Silvia Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Física Enrique Gaviola; Argentina.Fil: Menchón, Silvia Adriana. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Salas, Isabel. Consejo Superior de Investigaciones Científicas. Centro de Biología Molecular Severo Ochoa; España.Fil: Salas, Isabel. Universidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa; España.Fil: Salas, Isabel. Consejo Superior de Investigaciones Científicas. Centro de Biología Molecular Severo Ochoa; España.Fil: Munck, Sebastian. Katholieke Universiteit Leuven. Center for Human Genetics. VIB Center for the Biology of Disease; Bélgica.Fil: Herreras, Oscar. Consejo Superior de Investigaciones Científicas. Instituto Cajal. Departamento de Neurobiología Funcional y de Sistemas; España.Fil: Balschun, Detlef. Katholieke Universiteit Leuven. Faculty of Psychology and Educational Sciences. Laboratory of Biological Psychology; Bélgica.Fil: Dotti, Carlos Gerardo. Consejo Superior de Investigaciones Científicas. Centro de Biología Molecular Severo Ochoa; España.Fil: Dotti, Carlos Gerardo. Universidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa; España.Fil: Dotti, Carlos Gerardo. Katholieke Universiteit Leuven. Center for Human Genetics. VIB Center for the Biology of Disease; Bélgica.Biofísic

Location, number and factors associated with cerebral microbleeds in an Italian-British cohort of CADASIL patients.

BACKGROUND AND PURPOSE: The frequency, clinical correlates, and risk factors of cerebral microbleeds (CMB) in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) are still poorly known. We aimed at determining the location and number of CMB and their relationship with clinical manifestations, vascular risk factors, drugs, and other neuroimaging features in CADASIL patients. METHODS: We collected clinical data by means of a structured proforma and centrally evaluated CMB on magnetic resonance gradient echo sequences applying the Microbleed Anatomical Rating Scale in CADASIL patients seen in 2 referral centers in Italy and United Kingdom. RESULTS: We evaluated 125 patients. CMB were present in 34% of patients and their presence was strongly influenced by the age. Twenty-nine percent of the patients had CMB in deep subcortical location, 22% in a lobar location, and 18% in infratentorial regions. After adjustment for age, factors significantly associated with a higher total number of CMB were hemorrhagic stroke, dementia, urge incontinence, and statins use (this latter not confirmed by multivariate analysis). Infratentorial and deep CMB were associated with dementia and urge incontinence, lobar CMB with hemorrhagic stroke, dementia, and statins use. Unexpectedly, patients with migraine, with or without aura, had a lower total, deep, and lobar number of CMB than patients without migraine. DISCUSSION: CMB formation in CADASIL seems to increase with age. History of hemorrhagic stroke, dementia, urge incontinence, and statins use are associated with a higher number of CMB. However, these findings need to be confirmed by longitudinal studies

Progression of brain atrophy in spinocerebellar ataxia type 2: A longitudinal tensor-based morphometry study

Spinocerebellar ataxia type 2 (SCA2) is the second most frequent autosomal dominant inherited ataxia worldwide. We investigated the capability of magnetic resonance imaging (MRI) to track in vivo progression of brain atrophy in SCA2 by examining twice 10 SCA2 patients (mean interval 3.6 years) and 16 age- and gender-matched healthy controls (mean interval 3.3 years) on the same 1.5 T MRI scanner. We used T1-weighted images and tensor-based morphometry (TBM) to investigate volume changes and the Inherited Ataxia Clinical Rating Scale to assess the clinical deficit. With respect to controls, SCA2 patients showed significant higher atrophy rates in the midbrain, including substantia nigra, basis pontis, middle cerebellar peduncles and posterior medulla corresponding to the gracilis and cuneatus tracts and nuclei, cerebellar white matter (WM) and cortical gray matter (GM) in the inferior portions of the cerebellar hemisphers. No differences in WM or GM volume loss were observed in the supratentorial compartment. TBM findings did not correlate with modifications of the neurological deficit. In conclusion, MRI volumetry using TBM is capable of demonstrating the progression of pontocerebellar atrophy in SCA2, supporting a possible role of MRI as biomarker in future trials