Anthrax prophylaxis: recent advances and future directions

Anthrax is a serious, potentially fatal disease that can present in four distinct clinical patterns depending on the route of infection (cutaneous, gastrointestinal, pneumonic or injectional), so that effective strategies for prophylaxis and therapy are therefore required. Anthrax is a serious disease, requiring effective strategies for prophylaxis and therapy. This review addresses the complex mechanisms of pathogenesis employed by the bacterium and describes how, as understanding of these has developed over many years, so too have current strategies for vaccination and therapy. It covers the clinical and veterinary use of live attenuated strains of anthrax and the subsequent identification of protein sub-units for incorporation into vaccines, as well as combinations of protein sub-units with spore or other components. It also addresses the application of these vaccines for conventional prophylactic use, as well as post-exposure use in conjunction with antibiotics. It describes the licensed acellular vaccines AVA and AVP and discusses the prospects for a next generation of recombinant sub-unit vaccines for anthrax, balancing the regulatory requirement and current drive for highly defined vaccines, against the risk of losing the ‘danger’ signals required to induced protective immunity in the vaccinee. It considers novel approaches to reduce time to immunity by means of combining, for example, dendritic cell vaccination with conventional approaches and considers current opportunities for the immunotherapy of anthrax

Feynman's interpretation of quantum theory

A historically important but little known debate regarding the necessity and meaning of macroscopic superpositions, in particular those containing different gravitational fields, is discussed from a modern perspective.Comment: Published version for Eur.Phys.J. H. 15 pages pdf. Final version available at http://www.springerlink.com/openurl.asp?genre=article&id=doi:10.1140/epjh/e2011-10035-

Human exposure to naturally occurring Bacillus anthracis in the Kars region of Eastern Türkiye

Environmental contamination with Bacillus anthracis spores poses uncertain threats to human health. We undertook a study to determine whether inhabitants of the anthrax-endemic region of Kars in eastern Türkiye could develop immune responses to anthrax toxins without recognised clinical infection. We measured anti-PA and anti-LF IgG antibody concentrations by ELISA in serum from 279 volunteers, 105 of whom had previously diagnosed anthrax infection (100 cutaneous, 5 gastrointestinal). Of the 174 without history of infection, 72 had prior contact with anthrax-contaminated material. Individuals were classified according to demographic parameters, daily working environment, and residence type. All villages in this study had recorded previous animal or human anthrax cases. Stepwise regression analyses showed that prior clinical infection correlated strongly with concentrations at the upper end of the ranges observed for both antibodies. For anti-PA, being a butcher and duration of continuous exposure risk correlated with high concentrations, while being a veterinarian or shepherd, time since infection, and town residence correlated with low concentrations. For anti-LF, village residence correlated with high concentrations, while infection limited to fingers or thumbs correlated with low concentrations. Linear discriminant analysis identified antibody concentration profiles associated with known prior infection. Profiles least typical of prior infection were observed in urban dwellers with known previous infection and in veterinarians without history of infection. Four individuals without history of infection (two butchers, two rural dwellers) had profiles suggesting unrecognised prior infection. Healthy humans therefore appear able to tolerate low-level exposure to environmental B. anthracis spores without ill effect, but it remains to be determined whether this exposure is protective. These findings have implications for authorities tasked with reducing the risk posed to human health by spore-contaminated materials and environments

The Role of Direct Presentation by Donor Dendritic Cells in Rejection of Minor Histocompatibility Antigen-Mismatched Skin and Hematopoietic Cell Grafts

Background. The success of transplantation is hampered by rejection of the graft by alloreactive T cells. Donor dendritic cells (DC) have been shown to be required for direct priming of immune responses to antigens from major histocompatibility complex-mismatched grafts. However, for immune responses to major histocompatibility complex-matched, minor histocompatibility (H) antigen mismatched grafts, the magnitude of the T-cell response to directly presented antigens is reduced, and the indirect pathway is more important. Therefore, we aimed to investigate the requirement for donor DC to directly present antigen from minor H antigen mismatched skin and hematopoietic grafts.Methods. Langerhans cell-or conventional (c) DC-depleted skin or hematopoietic cells from male DC-specific diphtheria toxin receptor mice were grafted onto, or injected into, syngeneic female recipients, and survival of the male tissue was compared with nondepleted tissue. Activation of the alloreactive immune response was tracked by the expansion of T cells specific for male HY-derived epitopes.Results. Our data demonstrate that depletion of donor Langerhans cell, dermal cDC, or both from skin grafts prolongs their survival but does not prevent rejection. Extended survival correlates with delayed expansion of HY peptide-specific CD8(+) T cells. In addition, depletion of donor cDC delays rejection of male hematopoietic cells.Conclusions. Our results demonstrate for the first time that direct presentation of minor H antigens by donor DC is required for efficient rejection of skin and hematopoietic grafts by CD8(+) T cells. But, in the absence of donor DC, indirect presentation of minor antigens is sufficient to mediate the response

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Impact of HO2 aerosol uptake on radical levels and O3 production during summertime in Beijing

The impact of heterogeneous uptake of HO2 on aerosol surfaces on radical concentrations and the O3 production regime in Beijing in summertime was investigated. The uptake coefficient of HO2 onto aerosol surfaces, γHO2 , was calculated for the AIRPRO campaign in Beijing, in summer 2017, as a function of measured aerosol soluble copper concentration, [Cu2+]eff, aerosol liquid water content, [ALWC], and particulate matter concentration, [PM]. An average γHO2 across the entire campaign of 0.070 ± 0.035 was calculated, with values ranging from 0.002 to 0.15, and found to be significantly lower than the value of γHO2 = 0.2, commonly used in modelling studies. Using the calculated γHO2 values for the summer AIRPRO campaign, OH, HO2 and RO2 radical concentrations were modelled using a box model incorporating the Master Chemical Mechanism (v3.3.1), with and without the addition of γHO2 , and compared to the measured radical concentrations. The rate of destruction analysis showed the dominant HO2 loss pathway to be HO2 + NO for all NO concentrations across the summer Beijing campaign, with HO2 uptake contributing < 0.3 % to the total loss of HO2 on average. This result for Beijing summertime would suggest that under most conditions encountered, HO2 uptake onto aerosol surfaces is not important to consider when investigating increasing O3 production with decreasing [PM] across the North China Plain. At low [NO], however, i.e. < 0.1 ppb, which was often encountered in the afternoons, up to 29 % of modelled HO2 loss was due to HO2 uptake on aerosols when calculated γHO2 was included, even with the much lower γHO2 values compared to γHO2 = 0.2, a result which agrees with the aerosol-inhibited O3 regime recently proposed by Ivatt et al. (2022). As such it can be concluded that in cleaner environments, away from polluted urban centres where HO2 loss chemistry is not dominated by NO but where aerosol surface area is high still, changes in PM concentration and hence aerosol surface area could still have a significant effect on both overall HO2 concentration and the O3 production regime. Using modelled radical concentrations, the absolute O3 sensitivity to NOx and volatile organic compounds (VOCs) showed that, on average across the summer AIRPRO campaign, the O3 production regime remained VOC-limited, with the exception of a few days in the afternoon when the NO mixing ratio dropped low enough for the O3 regime to shift towards being NOx -limited. The O3 sensitivity to VOCs, the dominant regime during the summer AIRPRO campaign, was observed to decrease and shift towards a NOx -sensitive regime both when NO mixing ratio decreased and with the addition of aerosol uptake. This suggests that if [NOx ] continues to decrease in the future, ozone reduction policies focussing solely on NOx reductions may not be as efficient as expected if [PM] and, hence, HO2 uptake to aerosol surfaces continue to decrease. The addition of aerosol uptake into the model, for both the γHO2 calculated from measured data and when using a fixed value of γHO2 = 0.2, did not have a significant effect on the overall O3 production regime across the campaign. While not important for this campaign, aerosol uptake could be important for areas of lower NO concentration that are already in a NOx -sensitive regime

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Nafwaya fauya cibamu candi (Looking for my girl))

"I went to look for my girl, but they told me she had gone to the beer-hall. So I put on my best suit and took my bicycle called "Hummer sports" and went to the beer-hall to look for her. But I found her drinking with her friends and when they saw me, they put on dark glasses. "She came up to me and said "give me a kiss", but I refused saying: "You have accepted beer from these other men." Love song with guitar

Looking for my girl

Love song with guitar accompaniment

The Production, Communication, and Contestation of Physical Education Policy: The cases of Mississippi and Tennessee

The purpose of this study was to explore the production, communication, interpretation and contestation of new physical education (PE) and physical activity (PA) policy initiatives introduced in Mississippi and Tennessee for the academic year 2006-2007. These states provide a relevant context to study such issues, since Mississippi has the highest and Tennessee has the fifth-highest rate of childhood obesity in the United States (Trust for America\u27s Health, 2009). The social-ecological model was used as a theoretical framework to interpret the social, economic, temporal, and political interactions that shaped the development, interpretation, and implementation of these policies (Stokols, 1992). A multiple-level case study design (Yin, 2003) was adopted in which the policy process was analyzed and compared across eight high schools. We purposefully selected four high schools in each state that provided a broad range of contextual differences and collected data in real-time during a one-year period. We conducted 73 interviews with key stakeholders, including policymakers, school administrators, teachers and students, and observed PE lessons and school-based activities. The researchers identified themes from the data: Policy process; Expectation of compliance; Unfunded mandate; Problematic policy enactment; Academic pressure; Marginalized status of PE; Narrow PE curriculum; and Dislike of PE. Even though new PE and PA legislation had been passed in both states, no substantive change occurred in any of the schools during our study. This work moves beyond a superficial understanding of how policy initiatives impact PA and PE provisions within schools, particularly at the secondary level. We recommend the development of support systems within the school through the creation of clear goals, strategic plans, and professional development to implement new policy initiatives