Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt

Ionization by bulk heating of electrons in capacitive radio frequency atmospheric pressure microplasmas

Electron heating and ionization dynamics in capacitively coupled radio frequency (RF) atmospheric pressure microplasmas operated in helium are investigated by Particle in Cell simulations and semi-analytical modeling. A strong heating of electrons and ionization in the plasma bulk due to high bulk electric fields are observed at distinct times within the RF period. Based on the model the electric field is identified to be a drift field caused by a low electrical conductivity due to the high electron-neutral collision frequency at atmospheric pressure. Thus, the ionization is mainly caused by ohmic heating in this "Omega-mode". The phase of strongest bulk electric field and ionization is affected by the driving voltage amplitude. At high amplitudes, the plasma density is high, so that the sheath impedance is comparable to the bulk resistance. Thus, voltage and current are about 45{\deg} out of phase and maximum ionization is observed during sheath expansion with local maxima at the sheath edges. At low driving voltages, the plasma density is low and the discharge becomes more resistive resulting in a smaller phase shift of about 4{\deg}. Thus, maximum ionization occurs later within the RF period with a maximum in the discharge center. Significant analogies to electronegative low pressure macroscopic discharges operated in the Drift-Ambipolar mode are found, where similar mechanisms induced by a high electronegativity instead of a high collision frequency have been identified

Immunity in Society: Diverse Solutions to Common Problems

How do social animals, from insects to humans, limit the spread of disease by deploying community-level responses to pathogens? Active immunization of healthy ants by infected ants is one intriguing example

On inconsistency of experimental data on primary nuclei spectra with sea level muon intensity measurements

For the first time a complete set of the most recent direct data on primary cosmic ray spectra is used as input into calculations of muon flux at sea level in wide energy range $E_\mu=1-3\cdot10^5$ GeV. Computations have been performed with the CORSIKA/QGSJET and CORSIKA/VENUS codes. The comparison of the obtained muon intensity with the data of muon experiments shows, that measurements of primary nuclei spectra conform to sea level muon data only up to several tens of GeV and result in essential deficit of muons at higher energies. As it follows from our examination, uncertainties in muon flux measurements and in the description of nuclear cascades development are not suitable to explain this contradiction, and the only remaining factor, leading to this situation, is underestimation of primary light nuclei fluxes. We have considered systematic effects, that may distort the results of the primary cosmic ray measurements with the application of the emulsion chambers. We suggest, that re-examination of these measurements is required with the employment of different hadronic interaction models. Also, in our point of view, it is necessary to perform estimates of possible influence of the fact, that sizable fraction of events, identified as protons, actually are antiprotons. Study of these cosmic ray component begins to attract much attention, but today nothing definite is known for the energies $>40$ GeV. In any case, to realize whether the mentioned, or some other reasons are the sources of disagreement of the data on primaries with the data on muons, the indicated effects should be thoroughly analyzed

Filarial Parasites Develop Faster and Reproduce Earlier in Response to Host Immune Effectors That Determine Filarial Life Expectancy

During larval development, filarial nematodes adjust their lifelong reproductive strategy to the presence of anti-parasitic immune cells that determine host resistance and experimental vaccine efficacy

Parasite Evolution and Life History Theory

Beth F. Kochin is with Emory University, James J. Bull is with UT Austin, Rustom Antia is with Emory University.As a group, parasites are extraordinarily diverse. Even closely related parasites may behave very differently, infecting different host species, causing different pathologies, or infecting different tissues. For example, Escherichia coli bacteria, a typically harmless inhabitant of the human gut, can, in different forms, cause diarrhea, intestinal bleeding, urinary tract infections, kidney bleeding, meningitis, and other diseases. Underlying this diversity is evolution.This work is supported by the National Institutes of Health and the Fannie and John Hertz Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Cellular and Molecular Biolog

Современные тенденции в разработке эффективных комбикормов для рыб

The successful development of the fish industry in the Republic of Belarus requires the provision of aquaculture facilities with low-cost, high-quality, safe and effective feed. Institute of Fish Industry of the National Academy of Sciences of Belarus is developing new types of domestic raw materials of waste industry, in particular fish processing waste. This high-protein raw material is the best for freshwater fish, especially for valuable species. Currently, laboratory samples of fish hydrolyzate have been obtained, which can replace imported fish meal by 10–15 % in composition of compound feed for fish, which will make it possible to reduce the price of domestic feed by 7–10 %. Development of hydrolyzate from fish processing waste will create a closed cycle of fish processing with production of high-quality compound feed raw materials. A new treatment-and-prophylactic compound feed “Mix-Feed” and its specifications have been developed. Compound feed is intended for prevention and treatment of bacterial infections of carp fish, natural phytobiotic Mix-Oil is used in its composition in the amount of 600 g/t. Moisture-and-heat treatment modes of “Mix-Feed” compound feed was selected to preserve its activity. Conducted production tests at the republic's fish farms showed that compound feed “Mix-Feed” increases survival rate of carp by 80 % when fighting against bacterial infections. Compound feed “Mix-Feed” allows to eliminate the use of antibiotics for prevention and treatment of bacterial infections of carp, which allows to obtain environmentally friendly products being in demand in the world market. The new feed has already been used at large fish farms of the Republic of Belarus (fish farm “Volma” and OFH “Selets”). In cooperation with SPS “Armbiotechnology” of the National Academy of Sciences of Armenia and the National Polytechnic University of Armenia, natural preservative from wine production wastes is being developed. Tartaric acid benzylimide, isolated from wine production waste, showed high activity against conditionally pathogenic strains of salmonella and staphylococcus, causing high mortality of fish when using contaminated compound feed. In the future, this development will allow domestic feeds to become competitive in terms of storage period. Для успешного развития рыбной отрасли в Республике Беларусь требуется обеспечение объектов аквакультуры недорогими, качественными, безопасными и эффективными комбикормами. Институт рыбного хозяйства Национальной академии наук Беларуси разрабатывает новые виды отечественного сырья из отходов перерабатывающих производств, в частности отходов переработки рыбы. Данное высокобелковое сырье является наилучшим для пресноводной рыбы, особенно для ценных видов. В настоящее время получены лабораторные образцы рыбного гидролизата, который способен заменить импортную рыбную муку на 10–15 % в составе комбикормов для рыбы, что позволит удешевить отечественный комбикорм на 7–10 %. Разработка гидролизата из отходов переработки рыбы позволит создать замкнутый цикл переработки рыбы с получением высококачественного комбикормового сырья. Разработан новый лечебно-профилактический комбикорм «Микс-Корм» и технические условия на него. Комбикорм предназначен для профилактики и лечения бактериальных инфекций карповых рыб, в его составе используется натуральный фитобиотик «Микс-Оил» в количестве 600 г/т. Подобраны режимы влаготепловой обработки комбикорма «Микс-Корм» для сохранения его активности. Производственные испытания, проведенные в рыбхозах республики, показали, что комбикорм «Микс-Корм» повышает выживаемость карпа на 80 % при борьбе с бактериальными инфекциями. Комбикорм «Микс-Корм» позволяет исключить использование антибиотиков при профилактике и лечении бактериальных инфекций карпа, что дает возможность получать экологически чистую продукцию, востребованную на мировом рынке. Новый комбикорм уже используется крупными рыбхозами Республики Беларусь (рыбхоз «Волма» и ОРХ «Селец»). Совместно с НПЦ «Армбиотехнология» Национальной академии наук Республики Армения и Национальным политехничнским университетом Армении разрабатывается натуральный консервант из отходов винного производства. Бензилимид винной кислоты, выделенный из отходов винного производства, показал высокую активность в отношении условно-патогенных штаммов сальмонеллы и стафиллокока, вызывающих высокую смертность рыбы при использовании зараженных ими комбикормов. Данная разработка в перспективе позволит сделать отечественные комбикорма конкурентосособными по срокам хранения.

Sexuality, rights and personhood: tensions in a transnational world

<p>Abstract</p> <p>Background</p> <p>This article discusses what happens when normative ‘global’ discourses of rights and individuated sexual identity confront the messiness of ‘local’ realities. It considers the tensions that emerge when the relationship between sexual and social identities is not obvious and the implications of such tensions for public health and sexual rights activism. These questions are addressed through debates over the naming of male-to-male sexualities and desires in the context of globalization and the growth of a large NGO (non-governmental organization) sector in urban Bangladesh.</p> <p>Methods</p> <p>The material in the paper draws on a research project undertaken in 2008-9 in Dhaka, Bangladesh. A fundamental objective was to produce a contextualized understanding of sexuality in Dhaka city. Methods used included structured interviews, focus group discussions and informal conversations with a range of participants (students, factory workers, public health professionals and sexual minorities). The aim was to generate a conceptual and analytical framework around sexuality and rights rather than to undertake an empirical survey of any one population.</p> <p>Results</p> <p>As descriptors, globalized identity categories such as Men who have Sex with Men (MSM), used by public health providers, the state and donors; and gay/lesbian, invoked by human rights activists and transnational NGOs, are too narrow to capture the fluid and highly context-specific ways in which gender and sexually nonconforming persons understand themselves in Bangladesh. Further, class position mediates to a significant degree the reception, appropriation or rejection of transnational categories such as MSM and Lesbian, Gay, Bisexual, Transgender (LGBT). The tension is reflected in the sometimes fraught relations between service providers to MSM, the people they serve and an emerging group who identify as LGBT.</p> <p>Conclusion</p> <p>A simple politics of recognition will be inadequate to the task of promoting health and human rights for all; such a strategy would effectively exclude individuals who do not necessarily connect their sexual practices with a specific sexual or social identity.</p

The Chemokine CXCL12 Is Essential for the Clearance of the Filaria Litomosoides sigmodontis in Resistant Mice

Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms

Comparative genomics of the major parasitic worms

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms