316 research outputs found

    The Phenomenon of Cultural Genocide: History and Modernity

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    The article is dedicated to the study of the «cultural genocide» concept as one of the forms of the genocide crime in order to establish the content of culture as the object of the genocide crime. For this, the historical legal method and the method of case study were used (in particular the practice of destroying the culture of the peoples of the Ottoman Empire. Sri Lanka and Tibet for comparison with the possibility of designating them as a crime of cultural genocide, acting as an element of the genocide crime, or as a separate crime with a meaning different from physical and biological genocide). It is concluded that cultural genocide is not a new component of the genocide crime, but an integral part of genocidal policy, and may constitute the phases of pregenocide or postgenocide or act as a separate crime requiring early warning and suppression

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

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    <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

    Spatially resolved simulation of a radio frequency driven micro atmospheric pressure plasma jet and its effluent

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    Radio frequency driven plasma jets are frequently employed as efficient plasma sources for surface modification and other processes at atmospheric pressure. The radio-frequency driven micro atmospheric pressure plasma jet (μ\muAPPJ) is a particular variant of that concept whose geometry allows direct optical access. In this work, the characteristics of the μ\muAPPJ operated with a helium-oxygen mixture and its interaction with a helium environment are studied by numerical simulation. The density and temperature of the electrons, as well as the concentration of all reactive species are studied both in the jet itself and in its effluent. It is found that the effluent is essentially free of charge carriers but contains a substantial amount of activated oxygen (O, O3_3 and O2(1Δ)_2(^1\Delta)). The simulation results are verified by comparison with experimental data

    Synaptic abnormalities in the infralimbic cortex of a model of congenital depression

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    Multiple lines of evidence suggest that disturbances in excitatory transmission contribute to depression. Whether these defects involve the number, size, or composition of glutamatergic contacts is unclear. This study used recently introduced procedures for fluorescence deconvolution tomography in a well-studied rat model of congenital depression to characterize excitatory synapses in layer I of infralimbic cortex, a region involved in mood disorders, and of primary somatosensory cortex. Three groups were studied: (1) rats bred for learned helplessness (cLH); (2) rats resistant to learned helplessness (cNLH); and (3) control Sprague Dawley rats. In fields within infralimbic cortex, cLH rats had the same numerical density of synapses, immunolabeled for either the postsynaptic density (PSD) marker PSD95 or the presynaptic protein synaptophysin, as controls. However, PSD95 immunolabeling intensities were substantially lower in cLH rats, as were numerical densities of synapse-sized clusters of the AMPA receptor subunit GluA1. Similar but less pronounced differences (comparable numerical densities but reduced immunolabeling intensity for PSD95) were found in the somatosensory cortex. In contrast, non-helpless rats had 25% more PSDs than either cLH or control rats without any increase in synaptophysin-labeled terminal frequency. Compared with controls, both cLH and cNLH rats had fewer GABAergic contacts. These results indicate that congenital tendencies that increase or decrease depression-like behavior differentially affect excitatory synapses

    The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

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    Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

    Positivity in younger and in older age: Associations with future time perspective and socioemotional functioning

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    Aging has been associated with a motivational shift to positive over negative information (i.e., positivity effect), which is often explained by a limited future time perspective (FTP) within the framework of socioemotional selectivity theory (SST). However, whether a limited FTP functions similarly in younger and older adults, and whether inter-individual differences in socioemotional functioning are similarly associated with preference for positive information (i.e., positivity) is still not clear. We investigated younger (20–35 years, N = 73) and older (60–75 years, N = 56) adults’ gaze preferences on pairs of happy, angry, sad, and neutral faces using an eye-tracking system. We additionally assessed several parameters potentially underlying inter-individual differences in emotion processing such as FTP, stress, cognitive functioning, social support, emotion regulation, and well-being. While we found no age-related differences in positivity when the entire trial duration was considered, older adults showed longer fixations on the more positive face in later stages of processing (i.e., positivity shifts). This allocation of resources toward more positive stimuli might serve an emotion regulatory purpose and seems consistent with the SST. However, our findings suggest that age moderates the relationship between FTP and positivity shifts, such that the relationship between FTP and positivity preferences was negative in older, and positive in younger adults, potentially stemming from an age-related differential meaning of the FTP construct across age. Furthermore, our exploratory analyses showed that along with the age and FTP interaction, lower levels of worry also played a significant role in positivity shifts. We conclude that positivity effects cannot be solely explained by aging, or the associated reduced FTP per se, but is rather determined by a complex interplay of psychosocial and emotional features

    Magnetic nanomaterials for arterial embolization and hyperthermia of parenchymal organs tumors: A review

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    Magnetic hyperthermia (MH), proposed by R. K. Gilchrist in the middle of the last century as local hyperthermia, has nowadays become a recognized method for minimally invasive treatment of oncological diseases in combination with chemotherapy (ChT) and radiotherapy (RT). One type of MH is arterial embolization hyperthermia (AEH), intended for the presurgical treatment of primary inoperable and metastasized solid tumors of parenchymal organs. This method is based on hyperthermia after transcatheter arterial embolization of the tumor's vascular system with a mixture of magnetic particles and embolic agents. An important advantage of AEH lies in the double effect of embolotherapy, which blocks blood flow in the tumor, and MH, which eradicates cancer cells. Consequently, only the tumor undergoes thermal destruction. This review introduces the progress in the development of polymeric magnetic materials for application in AEH. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.8X20041; Ministerstvo Školství, Mládeže a Tělovýchovy, MŠMT: RP/CPC/2020/00

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

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    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

    The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing

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    Improvements in hygiene and health management have driven significant increases in human lifespan over the last 50 years. Frustratingly however, this extension of lifespan has not been matched by equivalent improvements in late-life health, not least due to the global pandemic in type-2 diabetes, obesity and cardiovascular disease, all ageing-associated conditions exacerbated and accelerated by widespread adoption of the high calorie Western diet (HCD). Recently, evidence has begun to emerge that parasitic worm infection might protect against such ageing-associated co-morbidities, as a serendipitous side-effect of their evolution of pro-survival, anti-inflammatory mechanisms. As a novel therapeutic strategy, we have therefore investigated the potential of ES-62, an anti-inflammatory secreted product of the filarial nematode Acanthocheilonema viteae, to improve healthspan (the period of life before diseases of ageing appear) by targeting the chronic inflammation that drives metabolic dysregulation underpinning ageing-induced ill-health. We administered ES-62 subcutaneously (at a dose of 1 μg/week) to C57BL/6J mice undergoing HCD-accelerated ageing throughout their lifespan, while subjecting the animals to analysis of 120 immunometabolic responses at various time-points. ES-62 improved a number of inflammatory parameters, but markedly, a range of pathophysiological, metabolic and microbiome parameters of ageing were also successfully targeted. Notably, ES-62-mediated promotion of healthspan in male and female HCD-mice was associated with different mechanisms and reflecting this, machine learning modelling identified sex-specific signatures predictive of ES-62 action against HCD-accelerated ageing. Remarkably, ES-62 substantially increased the median survival of male HCD-mice. This was not the case with female animals and unexpectedly, this difference between the two sexes could not be explained in terms of suppression of the chronic inflammation driving ageing, as ES-62 tended to be more effective in reducing this in female mice. Rather, the difference appeared to be associated with ES-62's additional ability to preferentially promote a healthier gut-metabolic tissue axis in male animals
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