5,829 research outputs found

    Dynamical generation of wormholes with charged fluids in quadratic Palatini gravity

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    The dynamical generation of wormholes within an extension of General Relativity (GR) containing (Planck's scale-suppressed) Ricci-squared terms is considered. The theory is formulated assuming the metric and connection to be independent (Palatini formalism) and is probed using a charged null fluid as a matter source. This has the following effect: starting from Minkowski space, when the flux is active the metric becomes a charged Vaidya-type one, and once the flux is switched off the metric settles down into a static configuration such that far from the Planck scale the geometry is virtually indistinguishable from that of the standard Reissner-Nordstr\"om solution of GR. However, the innermost region undergoes significant changes, as the GR singularity is generically replaced by a wormhole structure. Such a structure becomes completely regular for a certain charge-to-mass ratio. Moreover, the nontrivial topology of the wormhole allows to define a charge in terms of lines of force trapped in the topology such that the density of lines flowing across the wormhole throat becomes a universal constant. To the light of our results we comment on the physical significance of curvature divergences in this theory and the topology change issue, which support the view that space-time could have a foam-like microstructure pervaded by wormholes generated by quantum gravitational effects.Comment: 14 pages, 3 figures, revtex4-1 style. New content added on section VI. Other minor corrections introduced. Final version to appear in Phys. Rev.

    Hypogammaglobulinemia in BLT Humanized Mice – An Animal Model of Primary Antibody Deficiency

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    Primary antibody deficiencies present clinically as reduced or absent plasma antibodies without another identified disorder that could explain the low immunoglobulin levels. Bone marrow-liver-thymus (BLT) humanized mice also exhibit primary antibody deficiency or hypogammaglobulinemia. Comprehensive characterization of B cell development and differentiation in BLT mice revealed other key parallels with primary immunodeficiency patients. We found that B cell ontogeny was normal in the bone marrow of BLT mice but observed an absence of switched memory B cells in the periphery. PC-KLH immunizations led to the presence of switched memory B cells in immunized BLT mice although plasma cells producing PCor KLH- specific IgG were not detected in tissues. Overall, we have identified the following parallels between the humoral immune systems of primary antibody deficiency patients and those in BLT mice that make this in vivo model a robust and translational experimental platform for gaining a greater understanding of this heterogeneous array of humoral immunodeficiency disorders in humans: (i) hypogammaglobulinemia; (ii) normal B cell ontogeny in bone marrow; and (iii) poor antigen-specific IgG response to immunization. Furthermore, the development of strategies to overcome these humoral immune aberrations in BLT mice may in turn provide insights into the pathogenesis of some primary antibody deficiency patients which could lead to novel clinical interventions for improved humoral immune function

    Hypogammaglobulinemia in BLT Humanized Mice – An Animal Model of Primary Antibody Deficiency

    Get PDF
    Primary antibody deficiencies present clinically as reduced or absent plasma antibodies without another identified disorder that could explain the low immunoglobulin levels. Bone marrow-liver-thymus (BLT) humanized mice also exhibit primary antibody deficiency or hypogammaglobulinemia. Comprehensive characterization of B cell development and differentiation in BLT mice revealed other key parallels with primary immunodeficiency patients. We found that B cell ontogeny was normal in the bone marrow of BLT mice but observed an absence of switched memory B cells in the periphery. PC-KLH immunizations led to the presence of switched memory B cells in immunized BLT mice although plasma cells producing PC- or KLH- specific IgG were not detected in tissues. Overall, we have identified the following parallels between the humoral immune systems of primary antibody deficiency patients and those in BLT mice that make this in vivo model a robust and translational experimental platform for gaining a greater understanding of this heterogeneous array of humoral immunodeficiency disorders in humans: (i) hypogammaglobulinemia; (ii) normal B cell ontogeny in bone marrow; and (iii) poor antigen-specific IgG response to immunization. Furthermore, the development of strategies to overcome these humoral immune aberrations in BLT mice may in turn provide insights into the pathogenesis of some primary antibody deficiency patients which could lead to novel clinical interventions for improved humoral immune function

    Entropy based parametrization of soils: Models and Tools

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    Particle-size distribution (PSD) is a fundamental soil physical property. The PSD is commonly reported in terms of the mass percentages of sand, silt and clay present

    On the relationship between head circumference, brain size, prenatal long-chain PUFA/5-methyltetrahydrofolate supplementation and cognitive abilities during childhood

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    Head circumference in infants has been reported to predict brain size, total grey matter volume (GMV) and neurocognitive development. However, it is unknown whether it has predictive value on regional and subcortical brain volumes. We aimed to explore the relationship between several head circumference measurements since birth and distributions of GMV and subcortical volumes at later childhood. We examined seventy-four, Caucasian, singleton, term-born infants born to mothers randomised to receive fish oil and/or 5-methyltetrahydrofolate or placebo prenatal supplementation. We assessed head circumference at birth and at 4 and 10 years of age and cognitive abilities at 7 years of age. We obtained brain MRI at 10 years of age, on which we performed voxel-based morphometry, cortical surface extraction and subcortical segmentation. Analyses were controlled for sex, age, height, weight, family status, laterality and total intracranial volume. Prenatal supplementation did not affect head circumference at any age, cognitive abilities or total brain volumes. Head circumference at 4 years presented the highest correlation with total GMV, white matter volume and brain surface area, and was also strongly associated with GMV of frontal, temporal and occipital areas, as well as with caudate nucleus, globus pallidus, putamen and thalamus volumes. As relationships between brain volumes in childhood and several outcomes extend into adulthood, we have found that ages between 0 and 4 years as the optimal time for brain growth; postnatal factors might have the most relevant impact on structural maturation of certain cortical areas and subcortical nuclei, independent of prenatal supplementation

    Algal lipids reveal unprecedented warming rates in alpine areas of SW Europe during the industrial period

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    Alpine ecosystems of the southern Iberian Peninsula are among the most vulnerable and the first to respond to modern climate change in southwestern Europe. While major environmental shifts have occurred over the last similar to 1500 years in these alpine ecosystems, only changes in the recent centuries have led to abrupt environmental responses, but factors imposing the strongest stress have been unclear until now. To understand these environmental responses, this study, for the first time, has calibrated an algal lipid-derived temperature proxy (based on long-chain alkyl diols) to instrumental historical data extending alpine temperature reconstructions to 1500 years before present. These novel results highlight the enhanced effect of greenhouse gases on alpine temperatures during the last similar to 200 years and the long-term modulating role of solar forcing. This study also shows that the warming rate during the 20th century (similar to 0.18 degrees C per decade) was double that of the last stages of the Little Ice Age (similar to 0.09 degrees C per decade), even exceeding temperature trends of the high-altitude Alps during the 20th century. As a consequence, temperature exceeded the preindustrial record in the 1950s, and it has been one of the major forcing processes of the recent enhanced change in these alpine ecosystems from southern Iberia since then. Nevertheless, other factors reducing the snow and ice albedo (e.g., atmospheric deposition) may have influenced local glacier loss, since almost steady climate conditions predominated from the middle 19th century to the first decades of the 20th century.Peer reviewe

    Systemic Administration of Antiretrovirals Prior to Exposure Prevents Rectal and Intravenous HIV-1 Transmission in Humanized BLT Mice

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    Successful antiretroviral pre-exposure prophylaxis (PrEP) for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT). BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003) and intravenous (Chi square = 13, df = 1, p = 0.0003) HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS

    Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism

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    Objective: To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism. Methods: Hypervariable V3–V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n=33 and n=25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profles using bioinformatics in order to identify diferences in taxonomy and metabolic pathways. Results: We identifed a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifdobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_ UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabo‑ lism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed diferences in key bacterial enzymes involved in urate synthesis, degradation, and elimination. Conclusion: Our fndings revealed that taxonomic variations in the gut microbiome of gout patients with and with‑ out tophi might have a functional impact on urate metabolism. Keywords: Gout, Gut microbiota, Uric acid metabolis
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