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

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

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

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

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

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

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

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

Experimental Investigation of Flow and Coherent Properties of Excited Non-Circular Liquid Jets

Non-circular jet is identified as an efficient passive flow-control technique that attracts many research topics. The existence of twine-vortexes is the main reason for dissimilarity between circular and non-circular jets. Which also influences the production of droplets and satellites as well as the jet instability. This investigation presents instability analysis of liquid-gas interface as an applicable conception in free-jet flows. We experiment different jet geometries within a gas ambient in order to study their hydrodynamic behavior. These studies give an appropriate perception about contributing forces that play essential roles in fluid instability. We focus on varying viscosity and surface tension as our excitation techniques. These methods are vital to examine the key properties of non-circular jets such as breakup and decay length, axis-switching wavelength as well as produced droplets and satellites characteristics. First, instabilities of charged liquid jets are investigated by considering the interaction between electric and inertial forces. Also, the viscosity effect was studied for its interaction with the inertial and surface tension forces. In each case, liquid jet in-stability for various nozzle geometries over a specific range of jet velocity is examined. The obtained results illustrate that the geometry of nozzle has an important effect on jet instability. In addition, by increment of We number, the breakup and decay length as well as the axis-switching wavelength are raising. However, by the rise of twin-vortex number, the breakup length increases but the decay length and axis-switching wavelength decrease

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

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

Armenia and Belarus: caught between the EU's and Russia's conditionalities?

This article looks into Armenia's and Belarus’ engagement with the European Union's (EU) and Russia's conditionalities, the two EU Eastern Partnership (EaP) countries that are also members of the Russia-led Eurasian Economic Union (EAEU). While paying attention to political, economic (including energy and technical) as well as security dimensions of the EU's and Russia's approaches, as proposed in the present special section, the article demonstrates that the conditionalities extended by the EU and Russia to the two countries in question have differed. In their turn, Armenia and Belarus have reacted differently to Russia's and the EU's conditionalities. Against the backdrop of the changing significance ascribed to both the EU's and Russia's policies towards their common neighbourhood since the 1990s, the present contribution identifies and analyses factors that account for the diverging positions of Armenia and Belarus, including the type of regime, the geopolitical considerations, the stakes in the economic and energy spheres and the predisposition to integration. The article shows that in the resulting complex context, Armenia and Belarus have been able to influence the shape and content of the EU's and Russia's conditionalities, although in a different way and to a different extent.Ministry of Education and Science (UID/CPO/ 00758/2013