Immunization with surface immunogenic protein induces a decrease of vaginal colonization by group B Streptococcus in an experimental mouse model

The Group B streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis in developed countries and an emerging pathogen in adults. A neonatal infection occurs predominantly during the delivery by either inhalation or ingestion of contaminated secretions of the mother’s vagina. Maternal screening by rectovaginal GBS colonization at 35–37 weeks of gestation, with subsequent intra-partum antibiotic prophylaxis (IAP) at the onset of labor, is implemented in some countries to prevent newborn invasive by GBS. Currently, there are not vaccines to prevent the devastating consequences of GBS and a glycoconjugate vaccine is under clinical experimentation (Clinical Trials Phase III). The Surface Immunological Protein (SIP) of GBS is highly immunogenic and conserved between different serotypes of this bacterium. The SIP had been described to induce antibodies type IgG that induces protective immunity in animal model challenged intraperitoneally with GBS. Here we describe the immunization with SIP mixed with an AbISCO-100 adjuvant in mice model challenged to GBS vaginal infection. The vaccine has demonstrated to decrease the GBS colonization in infected mouse. The SIP immunization has also increased the circulating IgA, IgG and IgG2a levels against SIP and antigen-specific circulating levels of IFN- ƴ and IL–2. Moreover, transfer of serum and T cells from a vaccinated animal into a non-immunized animal induced immune protection to the animals from challenged GBS colonization of the vaginal tract. In conclusion, we have demonstrated that a simple and effective vaccine is able to prevent GBS colonization, where cellular immunity plays an important role. To our knowledge, is the first report the SIP-based vaccine reduces the vaginal GBS colonization in an animal model

Current Animal Models for Understanding the Pathology Caused by the Respiratory Syncytial Virus

The human respiratory syncytial virus (hRSV) is the main etiologic agent of severe lower respiratory tract infections that affect young children throughout the world, associated with significant morbidity and mortality, becoming a serious public health problem globally. Up to date, no licensed vaccines are available to prevent severe hRSV-induced disease, and the generation of safe-effective vaccines has been a challenging task, requiring constant biomedical research aimed to overcome this ailment. Among the difficulties presented by the study of this pathogen, it arises the fact that there is no single animal model that resembles all aspects of the human pathology, which is due to the specificity that this pathogen has for the human host. Thus, for the study of hRSV, different animal models might be employed, depending on the goal of the study. Of all the existing models, the murine model has been the most frequent model of choice for biomedical studies worldwide and has been of great importance at contributing to the development and understanding of vaccines and therapies against hRSV. The most notable use of the murine model is that it is very useful as a first approach in the development of vaccines or therapies such as monoclonal antibodies, suggesting in this way the direction that research could have in other preclinical models that have higher maintenance costs and more complex requirements in its management. However, several additional different models for studying hRSV, such as other rodents, mustelids, ruminants, and non-human primates, have been explored, offering advantages over the murine model. In this review, we discuss the various applications of animal models to the study of hRSV-induced disease and the advantages and disadvantages of each model, highlighting the potential of each model to elucidate different features of the pathology caused by the hRSV infection

Natural Islands for a 125 GeV Higgs in the scale-invariant NMSSM

We study whether a 125 GeV standard model-like Higgs boson can be accommodated within the scale-invariant NMSSM in a way that is natural in all respects, i.e., not only is the stop mass and hence its loop contribution to Higgs mass of natural size, but we do not allow significant tuning of NMSSM parameters as well. We pursue as much as possible an analytic approach which gives clear insights on various ways to accommodate such a Higgs mass, while conducting complementary numerical analyses. We consider both scenarios with singlet-like state being heavier and lighter than SM-like Higgs. With A-terms being small, we find for the NMSSM to be perturbative up to GUT scale, it is not possible to get 125 GeV Higgs mass, which is true even if we tune parameters of NMSSM. If we allow some of the couplings to become non-perturbative below the GUT scale, then the non-tuned option implies that the singlet self-coupling, kappa, is larger than the singlet-Higgs coupling, lambda, which itself is order 1. This leads to a Landau pole for these couplings close to the weak scale, in particular below ~10^4 TeV. In both the perturbative and non-perturbative NMSSM, allowing large A_lambda, A_kappa gives "more room" to accommodate a 125 GeV Higgs, but a tuning of these A-terms may be needed. In our analysis we also conduct a careful study of the constraints on the parameter space from requiring global stability of the desired vacuum fitting a 125 GeV Higgs, which is complementary to existing literature. In particular, as the singlet-Higgs coupling lambda increases, vacuum stability becomes more serious of an issue.Comment: 34 pages, 4 figures, references added, minor corrections to text and figures, version to be published in JHE

R-parity Conservation via the Stueckelberg Mechanism: LHC and Dark Matter Signals

We investigate the connection between the conservation of R-parity in supersymmetry and the Stueckelberg mechanism for the mass generation of the B-L vector gauge boson. It is shown that with universal boundary conditions for soft terms of sfermions in each family at the high scale and with the Stueckelberg mechanism for generating mass for the B-L gauge boson present in the theory, electric charge conservation guarantees the conservation of R-parity in the minimal B-L extended supersymmetric standard model. We also discuss non-minimal extensions. This includes extensions where the gauge symmetries arise with an additional U(1)_{B-L} x U(1)_X, where U(1)_X is a hidden sector gauge group. In this case the presence of the additional U(1)_X allows for a Z' gauge boson mass with B-L interactions to lie in the sub-TeV region overcoming the multi-TeV LEP constraints. The possible tests of the models at colliders and in dark matter experiments are analyzed including signals of a low mass Z' resonance and the production of spin zero bosons and their decays into two photons. In this model two types of dark matter candidates emerge which are Majorana and Dirac particles. Predictions are made for a possible simultaneous observation of new physics events in dark matter experiments and at the LHC.Comment: 38 pages, 7 fig

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Tree height integrated into pantropical forest biomass estimates

Copyright © 2012 European Geosciences Union. This is the published version available at http://www.biogeosciences.net/9/3381/2012/bg-9-3381-2012.htmlAboveground tropical tree biomass and carbon storage estimates commonly ignore tree height (H). We estimate the effect of incorporating H on tropics-wide forest biomass estimates in 327 plots across four continents using 42 656 H and diameter measurements and harvested trees from 20 sites to answer the following questions: 1. What is the best H-model form and geographic unit to include in biomass models to minimise site-level uncertainty in estimates of destructive biomass? 2. To what extent does including H estimates derived in (1) reduce uncertainty in biomass estimates across all 327 plots? 3. What effect does accounting for H have on plot- and continental-scale forest biomass estimates? The mean relative error in biomass estimates of destructively harvested trees when including H (mean 0.06), was half that when excluding H (mean 0.13). Power- and Weibull-H models provided the greatest reduction in uncertainty, with regional Weibull-H models preferred because they reduce uncertainty in smaller-diameter classes (≤40 cm D) that store about one-third of biomass per hectare in most forests. Propagating the relationships from destructively harvested tree biomass to each of the 327 plots from across the tropics shows that including H reduces errors from 41.8 Mg ha−1 (range 6.6 to 112.4) to 8.0 Mg ha−1 (−2.5 to 23.0). For all plots, aboveground live biomass was −52.2 Mg ha−1 (−82.0 to −20.3 bootstrapped 95% CI), or 13%, lower when including H estimates, with the greatest relative reductions in estimated biomass in forests of the Brazilian Shield, east Africa, and Australia, and relatively little change in the Guiana Shield, central Africa and southeast Asia. Appreciably different stand structure was observed among regions across the tropical continents, with some storing significantly more biomass in small diameter stems, which affects selection of the best height models to reduce uncertainty and biomass reductions due to H. After accounting for variation in H, total biomass per hectare is greatest in Australia, the Guiana Shield, Asia, central and east Africa, and lowest in east-central Amazonia, W. Africa, W. Amazonia, and the Brazilian Shield (descending order). Thus, if tropical forests span 1668 million km2 and store 285 Pg C (estimate including H), then applying our regional relationships implies that carbon storage is overestimated by 35 Pg C (31–39 bootstrapped 95% CI) if H is ignored, assuming that the sampled plots are an unbiased statistical representation of all tropical forest in terms of biomass and height factors. Our results show that tree H is an important allometric factor that needs to be included in future forest biomass estimates to reduce error in estimates of tropical carbon stocks and emissions due to deforestation

Expression Profiling of a Genetic Animal Model of Depression Reveals Novel Molecular Pathways Underlying Depressive-Like Behaviours

The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression.In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL) and control Flinders Depression Resistant (FRL) lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7) and serotonergic receptors (Htr1a, Htr2a) in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL.These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research

Evolutionary Heritage Influences Amazon Tree Ecology

Lineages tend to retain ecological characteristics of their ancestors through time. However, for some traits, selection during evolutionary history may have also played a role in determining trait values. To address the relative importance of these processes requires large-scale quantification of traits and evolutionary relationships among species. The Amazonian tree flora comprises a high diversity of angiosperm lineages and species with widely differing life-history characteristics, providing an excellent system to investigate the combined influences of evolutionary heritage and selection in determining trait variation. We used trait data related to the major axes of life-history variation among tropical trees (e.g. growth and mortality rates) from 577 inventory plots in closed-canopy forest, mapped onto a phylogenetic hypothesis spanning more than 300 genera including all major angiosperm clades to test for evolutionary constraints on traits. We found significant phylogenetic signal (PS) for all traits, consistent with evolutionarily related genera having more similar characteristics than expected by chance. Although there is also evidence for repeated evolution of pioneer and shade tolerant life-history strategies within independent lineages, the existence of significant PS allows clearer predictions of the links between evolutionary diversity, ecosystem function and the response of tropical forests to global change

Variation in stem mortality rates determines patterns of above-ground biomass in Amazonian forests: implications for dynamic global vegetation models

This is the final version of the article. Available from Wiley via the DOI in this record.Understanding the processes that determine above-ground biomass (AGB) in Amazonian forests is important for predicting the sensitivity of these ecosystems to environmental change and for designing and evaluating dynamic global vegetation models (DGVMs). AGB is determined by inputs from woody productivity [woody net primary productivity (NPP)] and the rate at which carbon is lost through tree mortality. Here, we test whether two direct metrics of tree mortality (the absolute rate of woody biomass loss and the rate of stem mortality) and/or woody NPP, control variation in AGB among 167 plots in intact forest across Amazonia. We then compare these relationships and the observed variation in AGB and woody NPP with the predictions of four DGVMs. The observations show that stem mortality rates, rather than absolute rates of woody biomass loss, are the most important predictor of AGB, which is consistent with the importance of stand size structure for determining spatial variation in AGB. The relationship between stem mortality rates and AGB varies among different regions of Amazonia, indicating that variation in wood density and height/diameter relationships also influences AGB. In contrast to previous findings, we find that woody NPP is not correlated with stem mortality rates and is weakly positively correlated with AGB. Across the four models, basin-wide average AGB is similar to the mean of the observations. However, the models consistently overestimate woody NPP and poorly represent the spatial patterns of both AGB and woody NPP estimated using plot data. In marked contrast to the observations, DGVMs typically show strong positive relationships between woody NPP and AGB. Resolving these differences will require incorporating forest size structure, mechanistic models of stem mortality and variation in functional composition in DGVMs.This paper is a product of the European Union's Seventh Framework Programme AMAZALERT project (282664). The field data used in this study have been generated by the RAINFOR network, which has been supported by a Gordon and Betty Moore Foundation grant, the European Union's Seventh Framework Programme projects 283080, ‘GEOCARBON’; and 282664, ‘AMAZALERT’; ERC grant ‘Tropical Forests in the Changing Earth System’), and Natural Environment Research Council (NERC) Urgency, Consortium and Standard Grants ‘AMAZONICA’ (NE/F005806/1), ‘TROBIT’ (NE/D005590/1) and ‘Niche Evolution of South American Trees’ (NE/I028122/1). Additional data were included from the Tropical Ecology Assessment and Monitoring (TEAM) Network – a collaboration between Conservation International, the Missouri Botanical Garden, the Smithsonian Institution and the Wildlife Conservation Society, and partly funded by these institutions, the Gordon and Betty Moore Foundation, and other donors. Fieldwork was also partially supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico of Brazil (CNPq), project Programa de Pesquisas Ecológicas de Longa Duração (PELD-403725/2012-7). A.R. acknowledges funding from the Helmholtz Alliance ‘Remote Sensing and Earth System Dynamics’; L.P., M.P.C. E.A. and M.T. are partially funded by the EU FP7 project ‘ROBIN’ (283093), with co-funding for E.A. from the Dutch Ministry of Economic Affairs (KB-14-003-030); B.C. [was supported in part by the US DOE (BER) NGEE-Tropics project (subcontract to LANL). O.L.P. is supported by an ERC Advanced Grant and is a Royal Society-Wolfson Research Merit Award holder. P.M. acknowledges support from ARC grant FT110100457 and NERC grants NE/J011002/1, and T.R.B. acknowledges support from a Leverhulme Trust Research Fellowship

Evolutionary Heritage Influences Amazon Tree Ecology

Lineages tend to retain ecological characteristics of their ancestors through time. However, for some traits, selection during evolutionary history may have also played a role in determining trait values. To address the relative importance of these processes requires large-scale quantification of traits and evolutionary relationships among species. The Amazonian tree flora comprises a high diversity of angiosperm lineages and species with widely differing life-history characteristics, providing an excellent system to investigate the combined influences of evolutionary heritage and selection in determining trait variation. We used trait data related to the major axes of life-history variation among tropical trees (e.g. growth and mortality rates) from 577 inventory plots in closed-canopy forest, mapped onto a phylogenetic hypothesis spanning more than 300 genera including all major angiosperm clades to test for evolutionary constraints on traits. We found significant phylogenetic signal (PS) for all traits, consistent with evolutionarily related genera having more similar characteristics than expected by chance. Although there is also evidence for repeated evolution of pioneer and shade tolerant life-history strategies within independent lineages, the existence of significant PS allows clearer predictions of the links between evolutionary diversity, ecosystem function and the response of tropical forests to global change