Within-host spatiotemporal dynamics of systemic Salmonella infection during and after antimicrobial treatment

$\textbf{Objectives:}$ We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic $\textit{Salmonella}$ infections. $\textbf{Methods:}$ We infected mice with isogenic molecularly tagged subpopulations of either a fast-growing WT or a slow-growing $\Delta$$\textit{aroC Salmonella}$ strain. We monitored viable bacterial numbers and fluctuations in the proportions of each bacterial subpopulation in spleen, liver, blood and mesenteric lymph nodes (MLNs) before, during and after the cessation of treatment with ampicillin and ciprofloxacin. $\textbf{Results:}$ Both antimicrobials induced a reduction in viable bacterial numbers in the spleen, liver and blood. This reduction was biphasic in infections with fast-growing bacteria, with a rapid initial reduction followed by a phase of lower effect. Conversely, a slow and gradual reduction of the bacterial load was seen in infections with the slow-growing strain, indicating a positive correlation between bacterial net growth rates and the efficacy of ampicillin and ciprofloxacin. The viable numbers of either bacterial strain remained constant in MLNs throughout the treatment with a relapse of the infection with WT bacteria occurring after cessation of the treatment. The frequency of each tagged bacterial subpopulation was similar in the spleen and liver, but different from that of the MLNs before, during and after treatment. $\textbf{Conclusions:}$ In $\textit{Salmonella}$ infections, bacterial growth rates correlate with treatment efficacy. MLNs are a site with a bacterial population structure different to those of the spleen and liver and where the total viable bacterial load remains largely unaffected by antimicrobials, but can resume growth after cessation of treatment.This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) grant number BB/M000982/1 (http://www.bbsrc.ac.uk/research/grants/grants/AwardDetails.aspx?FundingReference=BB/M000982/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Dynamics of apparent horizons in quantum gravitational collapse

We study the gravitational collapse of a massless scalar field within the effective scenario of loop quantum gravity. Classical singularity is avoided and replaced by a quantum bounce in this model. It is shown that, quantum gravity effects predict a threshold scale below which no horizon can form as the collapse evolves towards the bounce.Comment: Contribution to the Spanish Relativity Meeting in Portugal 2012 (ERE2012), Guimaraes, Portuga

A Sensitive and Quantitative Polymerase Chain Reaction-Based Cell Free In Vitro Non-Homologous End Joining Assay for Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for the entire lifespan of an organism. Maintenance of genomic stability is crucial for the preservation of HSCs, which depends on their efficient repair of DNA damage, particularly DNA double strand breaks (DSBs). Because of the paucity of HSCs and lack of sensitive assays, directly measuring the ability of HSCs to repair DSBs has been difficult. Therefore, we developed a sensitive and quantitative cell free in vitro non-homologous end joining (NHEJ) assay using linearized plasmids as the substrates and quantitative polymerase chain reaction (qPCR) technique. This assay can sensitively detect DSB repair via NHEJ in less than 1 µg 293T cell nuclear proteins or nuclear extracts from about 5,000 to 10,000 human BM CD34+ hematopoietic cells. Using this assay, we confirmed that human bone marrow HSCs (CD34+CD38− cells) are less proficient in the repair of DSBs by NHEJ than HPCs (CD34+CD38+ cells). In contrast, mouse quiescent HSCs (Pyronin-Ylow LKS+ cells) and cycling HSCs (Pyronin-Yhi LKS+ cells) repaired the damage more efficiently than HPCs (LKS− cells). The difference in the abilities of human and mouse HSCs and HPCs to repair DSBs through NHEJ is likely attributed to their differential expression of key NHEJ DNA damage repair genes such as LIG4. These findings suggest that the qPCR-based cell free in vitro NHEJ assay can be used to sensitively measure the ability of human and mouse HSCs to repair DSBs

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

Geographical limits of the Southeastern distribution of Aedes aegypti (Diptera, Culicidae) in Argentina

The current geographical distribution of Aedes aegypti in South America is dramatically expanding inside Argentina, reaching a wider distribution than during its early eradication in 1967. Simultaneously, cases of dengue have increased during the last few years, and the situation has been recently worsened by the confirmation of the presence of the different dengue serotypes simultaneously circulating in new regions. Here we report on the passive south-eastern dispersion of A. aegypti in Argentina.Fil: Díaz Nieto, Leonardo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biociencias Agrícolas y Ambientales. Grupo Vinculado al Centro de Estudios de la Biodiversidad y Biotecnología de Mar del Plata- INBA. Fundación para Investigaciones Biológicas Aplicadas; ArgentinaFil: Maciá, Arnaldo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; ArgentinaFil: Perotti, M. Alejandra. University of Reading. School of Biological Sciences; Reino UnidoFil: Berón, Corina Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biociencias Agrícolas y Ambientales. Grupo Vinculado al Centro de Estudios de la Biodiversidad y Biotecnología de Mar del Plata- INBA. Fundación para Investigaciones Biológicas Aplicadas; Argentin

Stability of Spatial Optical Solitons

We present a brief overview of the basic concepts of the soliton stability theory and discuss some characteristic examples of the instability-induced soliton dynamics, in application to spatial optical solitons described by the NLS-type nonlinear models and their generalizations. In particular, we demonstrate that the soliton internal modes are responsible for the appearance of the soliton instability, and outline an analytical approach based on a multi-scale asymptotic technique that allows to analyze the soliton dynamics near the marginal stability point. We also discuss some results of the rigorous linear stability analysis of fundamental solitary waves and nonlinear impurity modes. Finally, we demonstrate that multi-hump vector solitary waves may become stable in some nonlinear models, and discuss the examples of stable (1+1)-dimensional composite solitons and (2+1)-dimensional dipole-mode solitons in a model of two incoherently interacting optical beams.Comment: 34 pages, 9 figures; to be published in: "Spatial Optical Solitons", Eds. W. Torruellas and S. Trillo (Springer, New York

Lattice QCD determination of m_b, f_B and f_Bs with twisted mass Wilson fermions

We present a lattice QCD determination of the b quark mass and of the B and B_s decay constants, performed with N_f=2 twisted mass Wilson fermions, by simulating at four values of the lattice spacing. In order to study the b quark on the lattice, two methods are adopted in the present work, respectively based on suitable ratios with exactly known static limit and on the interpolation between relativistic data, evaluated in the charm mass region, and the static point, obtained by simulating the HQET on the lattice. The two methods provide results in good agreement. For the b quark mass in the MSbar scheme and for the decay constants we obtain m_b(m_b)=4.29(14) GeV, f_B=195(12) MeV, f_Bs=232(10) MeV and f_Bs/f_B=1.19(5). As a byproduct of the analysis we also obtain the results for the f_D and f_Ds decay constants: f_D=212(8) MeV, f_Ds=248(6) MeV and f_Ds/f_D=1.17(5).Comment: 23 pages, 10 figures, 2 tables. Added appendix showing the agreement of the data for the ratios with the HQE prediction. Matching JHEP published versio

Organism-sediment interactions govern post-hypoxia recovery of ecosystem functioning

Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning.