Modulation of Multiple Sclerosis and its Animal Model experimental Autoimmune encephalomyelitis by Food and Gut Microbiota

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research

Tree Content and Taper Functions for Loblolly and Slash Pine Trees Planted on Non-Old-Fields in East Texas

Equations are presented to estimate total or partial stem content in cubic feet and pounds (green or dry) for loblolly pine (Pinus taeda L.) and slash pine (Pinus elliotti Engelm.) trees planted on non-old-fields in East Texas. Equations are included to estimate the content of the complete tree (stem and branches). In addition, a set of compatible stem taper functions are described. South. j. Appl. For. 11(3):147-15

Multiple sclerosis is linked to MAPK(ERK) overactivity in microglia

Reassessment of published observations in patients with multiple sclerosis (MS) suggests a microglial malfunction due to inappropriate (over)activity of the mitogen-activated protein kinase pathway ERK (MAPKERK). These observations regard biochemistry as well as epigenetics, and all indicate involvement of this pathway. Recent preclinical research on neurodegeneration already pointed towards a role of MAPK pathways, in particular MAPKERK. This is important as microglia with overactive MAPK have been identified to disturb local oligodendrocytes which can lead to locoregional demyelination, hallmark of MS. This constitutes a new concept on pathophysiology of MS, besides the prevailing view, i.e., autoimmunity. Acknowledged risk factors for MS, such as EBV infection, hypovitaminosis D, and smoking, all downregulate MAPKERK negative feedback phosphatases that normally regulate MAPKERK activity. Consequently, these factors may contribute to inappropriate MAPKERK overactivity, and thereby to neurodegeneration. Also, MAPKERK overactivity in microglia, as a factor in the pathophysiology of MS, could explain ongoing neurodegeneration in MS patients despite optimized immunosuppressive or immunomodulatory treatment. Currently, for these patients with progressive disease, no effective treatment exists. In such refractory MS, targeting the cause of overactive MAPKERK in microglia merits further investigation as this phenomenon may imply a novel treatment approach

Identification of F-box only protein 7 as a negative regulator of NF-kappaB signalling.

The nuclear factor κB (NF-κB) signalling pathway controls important cellular events such as cell proliferation, differentiation, apoptosis and immune responses. Pathway activation occurs rapidly upon TNFα stimulation and is highly dependent on ubiquitination events. Using cytoplasmic to nuclear translocation of the NF-κB transcription factor family member p65 as a read-out, we screened a synthetic siRNA library targeting enzymes involved in ubiquitin conjugation and de-conjugation for modifiers of regulatory ubiquitination events in NF-κB signalling. We identified F-box protein only 7 (FBXO7), a component of Skp, Cullin, F-box (SCF)-ubiquitin ligase complexes, as a negative regulator of NF-κB signalling. F-box protein only 7 binds to, and mediates ubiquitin conjugation to cIAP1 and TRAF2, resulting in decreased RIP1 ubiquitination and lowered NF-κB signalling activity

Evolution of correlated complexity in the radically different courtship signals of birds-of-paradise

This is the author accepted manuscript. The final version is available from Public Library of Science (PLoS) via the DOI in this record.Data accessibility: Data for primary analyses are included in S1 Data file.Ornaments used in courtship often vary wildly among species, reflecting the evolutionary interplay between mate preference functions and the constraints imposed by natural selection. Consequently, understanding the evolutionary dynamics responsible for ornament diversification has been a longstanding challenge in evolutionary biology. However, comparing radically different ornaments across species, as well as different classes of ornaments within species, is a profound challenge to understanding diversification of sexual signals. Using novel methods and a unique natural history dataset, we explore evolutionary patterns of ornament evolution in a group – the birds-of-paradise – exhibiting dramatic phenotypic diversification widely assumed to be driven by sexual selection. Rather than the trade-off between ornament types originally envisioned by Darwin and Wallace, we found positive correlations among cross-modal (visual/acoustic) signals indicating functional integration of ornamental traits into a composite unit – the courtship phenotype. Furthermore, given the broad theoretical and empirical support for the idea that systemic robustness – functional overlap and interdependency – promotes evolutionary innovation, we posit that birds-of-paradise have radiated extensively through ornamental phenotype space as a consequence of the robustness in the courtship phenotype that we document at a phylogenetic scale. We suggest that the degree of robustness in courtship phenotypes among taxa can provide new insights into the relative influence of sexual and natural selection on phenotypic radiations

Stressed backbone and elasticity of random central-force systems

We use a new algorithm to find the stress-carrying backbone of ``generic'' site-diluted triangular lattices of up to 10^6 sites. Generic lattices can be made by randomly displacing the sites of a regular lattice. The percolation threshold is Pc=0.6975 +/- 0.0003, the correlation length exponent \nu =1.16 +/- 0.03 and the fractal dimension of the backbone Db=1.78 +/- 0.02. The number of ``critical bonds'' (if you remove them rigidity is lost) on the backbone scales as L^{x}, with x=0.85 +/- 0.05. The Young's modulus is also calculated.Comment: 5 pages, 5 figures, uses epsfi

Combinatorial models of rigidity and renormalization

We first introduce the percolation problems associated with the graph theoretical concepts of $(k,l)$-sparsity, and make contact with the physical concepts of ordinary and rigidity percolation. We then devise a renormalization transformation for $(k,l)$-percolation problems, and investigate its domain of validity. In particular, we show that it allows an exact solution of $(k,l)$-percolation problems on hierarchical graphs, for $k\leq l<2k$. We introduce and solve by renormalization such a model, which has the interesting feature of showing both ordinary percolation and rigidity percolation phase transitions, depending on the values of the parameters.Comment: 22 pages, 6 figure

Nutritional and ecological perspectives of the interrelationships between diet and the gut microbiome in multiple sclerosis:Insights from marmosets

Studies in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis, have shown potential links between diet components, microbiome composition, and modulation of immune responses. In this review, we reanalyze and discuss findings in an outbred marmoset EAE model in which a yogurt-based dietary supplement decreased disease frequency and severity. We show that although diet has detectable effects on the fecal microbiome, microbiome changes are more strongly associated with the EAE development. Using an ecological framework, we further show that the dominant factors influencing the gut microbiota were marmoset sibling pair and experimental time point. These findings emphasize challenges in assigning cause-and-effect relationships in studies of diet-microbiome-host interactions and differentiating the diet effects from other environmental, stochastic, and host-related factors. We advocate for animal experiments to be designed to allow causal inferences of the microbiota's role in pathology while considering the complex ecological processes that shape microbial communities

B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by autoimmune-mediated demyelination and neurodegeneration. The CNS of patients with MS harbors expanded clones of antigen-experienced B cells that reside in distinct compartments including the meninges, cerebrospinal fluid (CSF), and parenchyma. It is not understood whether this immune infiltrate initiates its development in the CNS or in peripheral tissues. B cells in the CSF can exchange with those in peripheral blood, implying that CNS B cells may have access to lymphoid tissue that may be the specific compartment(s) in which CNS-resident B cells encounter antigen and experience affinity maturation. Paired tissues were used to determine whether the B cells that populate the CNS mature in the draining cervical lymph nodes (CLNs). High-throughput sequencing of the antibody repertoire demonstrated that clonally expanded B cells were present in both compartments. Founding members of clones were more often found in the draining CLNs. More mature clonal members derived from these founders were observed in the draining CLNs and also in the CNS, including lesions. These data provide new evidence that B cells traffic freely across the tissue barrier, with the majority of B cell maturation occurring outside of the CNS in the secondary lymphoid tissue. Our study may aid in further defining the mechanisms of immunomodulatory therapies that either deplete circulating B cells or affect the intrathecal B cell compartment by inhibiting lymphocyte transmigration into the CNS

Global diversity and balancing selection of 23 leading Plasmodium falciparum candidate vaccine antigens

Investigation of the diversity of malaria parasite antigens can help prioritize and validate them as vaccine candidates and identify the most common variants for inclusion in vaccine formulations. Studies of vaccine candidates of the most virulent human malaria parasite, Plasmodium falciparum, have focused on a handful of well-known antigens, while several others have never been studied. Here we examine the global diversity and population structure of leading vaccine candidate antigens of P. falciparum using the MalariaGEN Pf3K (version 5.1) resource, comprising more than 2600 genomes from 15 malaria endemic countries. A stringent variant calling pipeline was used to extract high quality antigen gene 'haplotypes' from the global dataset and a new R-package named VaxPack was used to streamline population genetic analyses. In addition, a newly developed algorithm that enables spatial averaging of selection pressure on 3D protein structures was applied to the dataset. We analysed the genes encoding 23 leading and novel candidate malaria vaccine antigens including csp, trap, eba175, ama1, rh5, and CelTOS. Our analysis shows that current malaria vaccine formulations are based on rare haplotypes and thus may have limited efficacy against natural parasite populations. High levels of diversity with evidence of balancing selection was detected for most of the erythrocytic and pre-erythrocytic antigens. Measures of natural selection were then mapped to 3D protein structures to predict targets of functional antibodies. For some antigens, geographical variation in the intensity and distribution of these signals on the 3D structure suggests adaptation to different human host or mosquito vector populations. This study provides an essential framework for the diversity of P. falciparum antigens to be considered in the design of the next generation of malaria vaccines