The FlagT4G Vaccine Confers a Strong and Regulated Immunity and Early Virological Protection against Classical Swine Fever

Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination, mostly using vaccines that do not allow for differentiation of vaccinated from infected animals (DIVA). FlagT4G vaccine is a novel candidate that confers robust immunity and shows DIVA capabilities. The present study assessed the immune response elicited by FlagT4G and its capacity to protect pigs for a short time after vaccination. Five days after a single dose of FlagT4G vaccine, animals were challenged with a highly virulent CSFV strain. A strong, but regulated, interferon-α response was found after vaccination. Vaccinated animals showed clinical and virological protection against the challenge, in the absence of antibody response at 5 days post-vaccination. Upon challenge, a rapid rise in the titers of CSFV neutralizing antibodies and an increase in the IFN-γ producing cells were noticed in all vaccinated-challenged pigs. Meanwhile, unvaccinated pigs showed severe clinical signs and high viral replication, being euthanized before the end of the trial. These animals were unable to generate neutralizing antibodies and IFN-γ responses after the CSFV challenge. The results from the present study assert the fast and efficient protection by FlagT4G, a highly promising tool for CSFV control worldwide.info:eu-repo/semantics/publishedVersio

The FlagT4G Vaccine Confers a Strong and Regulated Immunity and Early Virological Protection against Classical Swine Fever

Altres ajuts: Generalitat de Catalunya, programa Cerca RTI2018-100887-B-I00Control of classical swine fever virus (CSFV) in endemic countries relies on vaccination, mostly using vaccines that do not allow for differentiation of vaccinated from infected animals (DIVA). FlagT4G vaccine is a novel candidate that confers robust immunity and shows DIVA capabilities. The present study assessed the immune response elicited by FlagT4G and its capacity to protect pigs for a short time after vaccination. Five days after a single dose of FlagT4G vaccine, animals were challenged with a highly virulent CSFV strain. A strong, but regulated, interferon-α response was found after vaccination. Vaccinated animals showed clinical and virological protection against the challenge, in the absence of antibody response at 5 days post-vaccination. Upon challenge, a rapid rise in the titers of CSFV neutralizing antibodies and an increase in the IFN-γ producing cells were noticed in all vaccinated-challenged pigs. Meanwhile, unvaccinated pigs showed severe clinical signs and high viral replication, being euthanized before the end of the trial. These animals were unable to generate neutralizing antibodies and IFN-γ responses after the CSFV challenge. The results from the present study assert the fast and efficient protection by FlagT4G, a highly promising tool for CSFV control worldwide

Mechanisms of action of Methylthioadenosine: pathways implicated in neuroprotection in models of Multiple Sclerosis and other neurological diseases

From 5th European Workshop on Immune-Mediated Inflammatory Diseases (Sitges-Barcelona, Spain. 1-3 December 2010)Background Methylthioadenosine (MTA) has anti-oxidant and anti-proliferative properties and was shown to induce cell protection in hepatic cells. We previously demonstrated that exert immunomodulatory and neuroprotective effects in the animal model of Multiple Sclerosis (MS) and other neurological diseases like Parkinson disease, stroke and Epilepsy. Objective To study the mechanisms of action and different pathways implicated in the neuroprotective effect of MTA in neurological diseases. Methods RN22 (Schwnoma cell line) and PC12 (Pheochromocytoma cell line) were used to test the neuroprotective activity of MTA against stress in RN22 and to differentiate neurites in PC12. BV2 cells were used to test the effect of MTA in microglia. Organotypic cerebellum cultures were used to determine MTA effect in demyelination/remyelination. Luminex technology, western blot and ELISA were used in order to study the phosphorylated state of different pathways (AkT/PKB, ERK/MAPK, P38/SAPK or STAT3) and to determine the amount of different cytokines (IL-1β and TNF-α). Ros determination was also done by fluorescence determination. Results In vitro studies revealed that MTA protection against different stresses and its capacity to differentiate neurites implies pathways like ERK/MAPK, P38/SAPK or STAT3. MTA neuroprotective capacity is also related with its ability to reduce ROS production and oxidative stress. MTA was shown to protect against demyelination in cerebellum organotypic cultures treated with LPS or Lysolecithin. Conclusions MTA is neuroprotective in models of MS, Parkinson disease, stroke or Epilepsy. This neuroprotective effect depends on its capacity to protect against demyelination, its anti-oxidant effect and the activation of pathways related with protection against stress and production of neurite differentiation

Pere Alberch's developmental morphospaces and the evolution of cognition

In this article we argue for an extension of Pere Alberch's notion of developmental morphospace into the realm of cognition and introduce the notion of cognitive phenotype as a new tool for the evolutionary and developmental study of cognitive abilities

A role of mitochondrial complex II defects in genetic models of Huntington's disease expressing N-terminal fragments of mutant huntingtin.

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal expansion of a CAG repeat encoding a polyglutamine tract in the huntingtin (Htt) protein. The mutation leads to neuronal death through mechanisms which are still unknown. One hypothesis is that mitochondrial defects may play a key role. In support of this, the activity of mitochondrial complex II (C-II) is preferentially reduced in the striatum of HD patients. Here, we studied C-II expression in different genetic models of HD expressing N-terminal fragments of mutant Htt (mHtt). Western blot analysis showed that the expression of the 30 kDa Iron-Sulfur (Ip) subunit of C-II was significantly reduced in the striatum of the R6/1 transgenic mice, while the levels of the FAD containing catalytic 70 kDa subunit (Fp) were not significantly changed. Blue native gel analysis showed that the assembly of C-II in mitochondria was altered early in N171-82Q transgenic mice. Early loco-regional reduction in C-II activity and Ip protein expression was also demonstrated in a rat model of HD using intrastriatal injection of lentiviral vectors encoding mHtt. Infection of the rat striatum with a lentiviral vector coding the C-II Ip or Fp subunits induced a significant overexpression of these proteins that led to significant neuroprotection of striatal neurons against mHtt neurotoxicity. These results obtained in vivo support the hypothesis that structural and functional alterations of C-II induced by mHtt may play a critical role in the degeneration of striatal neurons in HD and that mitochondrial-targeted therapies may be useful in its treatment

Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy

How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues. In addition, the AnNA of the limbs of a trisomy 18 human fetus strongly supports Pere Alberch's ill-named "logic of monsters" hypothesis, and contradicts the commonly accepted idea that birth defects often lead to lower integration (i.e. more parcellation) of anatomical structures

The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

Age-dependent maintenance of motor control and corticostriatal innervation by death receptor 3

Death receptor 3 is a proinflammatory member of the immunomodulatory tumor necrosis factor receptor superfamily, which has been implicated in several inflammatory diseases such as arthritis and inflammatory bowel disease. Intriguingly however, constitutive DR3 expression has been detected in the brains of mice, rats, and humans, although its neurological function remains unknown. By mapping the normal brain expression pattern of DR3, we found that DR3 is expressed specifically by cells of the neuron lineage in a developmentally regulated and region-specific pattern. Behavioral studies on DR3-deficient (DR3(ko)) mice showed that constitutive neuronal DR3 expression was required for stable motor control function in the aging adult. DR3(ko) mice progressively developed behavioral defects characterized by altered gait, dyskinesia, and hyperactivity, which were associated with elevated dopamine and lower serotonin levels in the striatum. Importantly, retrograde tracing showed that absence of DR3 expression led to the loss of corticostriatal innervation without significant neuronal loss in aged DR3(ko) mice. These studies indicate that DR3 plays a key nonredundant role in the retention of normal motor control function during aging in mice and implicate DR3 in progressive neurological disease

Bifurcating spatially heterogeneous solutions in a chemotaxis model for biological pattern formation

We consider a simple cell-chemotaxis model for spatial pattern formation on two-dimensional domains proposed by Oster and Murray (1989,J. exp. Zool. 251, 186–202). We determine finite-amplitude, steady-state, spatially heterogeneous solutions and study the effect of domain growth on the resulting patterns. We also investigate in-depth bifurcating solutions as the chemotactic parameter varies. This numerical study shows that this deceptively simple-chemotaxis model can produce a surprisingly rich spectrum of complex spatial patterns

Hierarchy Theory of Evolution and the Extended Evolutionary Synthesis: Some Epistemic Bridges, Some Conceptual Rifts

Contemporary evolutionary biology comprises a plural landscape of multiple co-existent conceptual frameworks and strenuous voices that disagree on the nature and scope of evolutionary theory. Since the mid-eighties, some of these conceptual frameworks have denounced the ontologies of the Modern Synthesis and of the updated Standard Theory of Evolution as unfinished or even flawed. In this paper, we analyze and compare two of those conceptual frameworks, namely Niles Eldredge’s Hierarchy Theory of Evolution (with its extended ontology of evolutionary entities) and the Extended Evolutionary Synthesis (with its proposal of an extended ontology of evolutionary processes), in an attempt to map some epistemic bridges (e.g. compatible views of causation; niche construction) and some conceptual rifts (e.g. extra-genetic inheritance; different perspectives on macroevolution; contrasting standpoints held in the “externalism–internalism” debate) that exist between them. This paper seeks to encourage theoretical, philosophical and historiographical discussions about pluralism or the possible unification of contemporary evolutionary biology