IT’S THE LITTLE THINGS: AN EXPLORATION OF SMALL RNAS AND SELFISH GENETIC ELEMENTS OF THE HUMAN BACTERIAL PATHOGENS COXIELLA BURNETII AND BARTONELLA BACILLIFORMIS

Coxiella burnetii is a Gram-negative gammaproteobacterium and zoonotic agent of Q fever in humans. Previous work in our lab has demonstrated that C. burnetii codes for several small RNAs (sRNAs) that are differentially expressed between in vivo and in vitro growth conditions. sRNAs serve as post-transcriptional regulatory effectors involved in the control of nearly all biological processes. We demonstrated that several of the identified sRNAs, namely Coxiella burnetii small RNA 3 (CbsR3), Cbsr13, and CbsR16, represent members of two novel families of miniature inverted-repeat transposable elements (MITEs), termed QMITE1 and QMITE2. Furthermore, we have characterized a highly expressed, infection-specific sRNA, CbsR12, and have determined that it is necessary for expansion of the C. burnetii intracellular niche in a human monocyte-derived alveolar macrophage cell line. We have determined that CbsR12 may participate in broad gene regulation by acting as an RNA sponge for the global regulatory RNA-binding protein CsrA. Additionally, CbsR12 is a trans-acting sRNA that targets transcripts of the carA, metK, and cvpD genes in vitro and in vivo. Bartonella bacilliformis is a Gram-negative alphaproteobacterium and the etiological agent of Carrión\u27s disease in humans. B. bacilliformis is spread between humans through the bite of female phlebotomine sand flies. As a result, the pathogen encounters significant environmental shifts during its life cycle, including changes in pH and temperature. Bacterial sRNAs can serve as a means of rapid regulation under shifting environmental conditions. We therefore performed total RNA-sequencing analyses on B. bacilliformis grown in vitro then shifted to one of ten distinct conditions that simulate various environments encountered by the pathogen during its life cycle. From this, we identified 160 sRNAs significantly expressed under at least one of the conditions tested. Northern blot analysis was used to confirm the expression of eight novel sRNAs. We also characterized a Bartonella bacilliformis group I intron (BbgpI) that disrupts an un-annotated tRNACCUArg gene and determined that the intron splices in vivo and self-splices in vitro. Furthermore, we verified the predicted molecular targeting of a sand fly-specific sRNA, Bartonella bacilliformis small RNA 9 (BbsR9), to transcripts of the ftsH, nuoF, and gcvT genes, in vitro

The Physical State of the British Working Class, 1870-1914: Evidence from Army Recruits

It is easier to discover why people died in the past than how healthy they were during their lives. However, in both Europe and North America, much evidence survives about the health of young males from the medical examination of recruits to the armed forces. The paper discusses the possibility of generalizing from one such source, that of British volunteer recruits, to the health of the male working class. It concludes that the source is not seriously biassed and that, after some statistical correction, the data suggest a gradual improvement in the nutritional status, measured by average height, of the British working class.This finding contradicts much contemporary opinion that the British were physically deteriorating in the late nineteenth century.

Study of the luminous blue variable star candidate G26.47+0.02 and its environment

The luminous blue variable (LBV) stars are peculiar very massive stars. The study of these stellar objects and their surroundings is important for understanding the evolution of massive stars and its effects on the interstellar medium. We study the LBV star candidate G26.47+0.02. Using several large-scale surveys in different frequencies we performed a multiwavelength study of G26.47+0.02 and its surroundings. We found a molecular shell (seen in the 13CO J=1-0 line) that partially surrounds the mid-infrared nebula of G26.47+0.02, which suggests an interaction between the strong stellar winds and the molecular gas. From the HI absorption and the molecular gas study we conclude that G26.47+0.02 is located at a distance of ~4.8 kpc. The radio continuum analysis shows a both thermal and non-thermal emission toward this LBV candidate, pointing to wind-wind collision shocks from a binary system. This hypothesis is supported by a search of near-IR sources and the Chandra X-ray analysis. Additional multiwavelength and long-term observations are needed to detect some possible variable behavior, and if that is found, to confirm the binary nature of the system.Comment: accepted in A&A 01/05/201

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Production of IFN-β during Listeria monocytogenes Infection Is Restricted to Monocyte/Macrophage Lineage

The family of type I interferons (IFN), which consists of several IFN-α and one IFN-β, are produced not only after stimulation by viruses, but also after infection with non-viral pathogens. In the course of bacterial infections, these cytokines could be beneficial or detrimental. IFN-β is the primary member of type I IFN that initiates a cascade of IFN-α production. Here we addressed the question which cells are responsible for IFN-β expression after infection with the intracellular pathogen Listeria monocytogenes by using a genetic approach. By means of newly established reporter mice, maximum of IFN-β expression was observed at 24 hours post infection in spleen and, surprisingly, 48 hours post infection in colonized cervical and inguinal lymph nodes. Colonization of lymph nodes was independent of the type I IFN signaling, as well as bacterial dose and strain. Using cell specific reporter function and conditional deletions we could define cells expressing LysM as the major IFN-β producers, with cells formerly defined as Tip-DCs being the highest. Neutrophilic granulocytes, dendritic cells and plasmacytoid dendritic cells did not significantly contribute to type I IFN production

Design of PI controller with input constraint: application on blending process

Because of their simplicity, reliability and effectiveness, proportional–integral–derivative (PID) controllers remain the most widely used controllers in the process industries. Actuator saturation is among the most common and significant problem in control systems design. Normal PID controller does not take this into consideration. Normally, an anti‐windup compensator is employed in the system to overcome the problem. In this contribution, a new set of controller tuning relations is developed to tune the PI controller when the system is under saturation. The blending process was described as first order plus time delay (FOPTD) process and an expression is developed for saturation level, U as a function of controller gain, Kc with the range of R 0.4–2 (ratio of time delay to time constant). The proposed tuning rule relate the parameters of the controller to the parameters of a FOPTD model of the plant to a step change in the set point. The proposed method was applied to PI controller and tested on the process of blending system of sweetened condensed milk. The performance of the controller with various tuning formulae incorporated with classical anti‐windup strategies has been compared. The simulation results showed that the proposed method could give satisfactory performance in controlling the process