Distinctive cellular response to aluminum based adjuvants.

Aluminum-based adjuvants (ABAs) are used in human vaccines to enhance the magnitude of protective immune responses elicited against specific pathogens. One hypothesis is that stress signals released by aluminum-exposed necrotic cells play a role in modulating an immune response that contributes to the adjuvant's effectiveness. We hypothesized that aluminum adjuvant-induced necrosis would be similar irrespective of cellular origin or composition of the adjuvant. To test this hypothesis, human macrophages derived from peripheral monocytic cell line (THP-1) and cells derived from the human brain (primary astrocytes) were evaluated. Three commercially available formulations of ABAs (Alhydrogel, Imject alum, and Adju-Phos) were examined. Alum was also used as a reference. Cell viability, reactive oxygen species formation, and production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were quantified. Cells were exposed to different concentrations (10-100 μg/mL) of the adjuvants for 24 h or 72 h. The two FDA approved adjuvants (Alhydrogel and Adju-Phos) decreased cell viability in both cell types. At the 72 h time point, the decrease in viability was accompanied with increased ROS formation. The size of the aluminum agglomerates was not relatable to the changes observed. After exposure to ABAs, astrocytes and macrophages presented a distinct profile of cytokine secretion which may relate to the function and unique characteristics of each cell type. These variations indicate that aluminum adjuvants may have differing capability of activating cells of different origin and thus their utility in specific vaccine design should be carefully assessed for optimum efficacy

Взаємодія архетипних систем в українських, польських, староанглійських і кельтських загадках(на матеріалі праць І.Я.Франка та Ексетерської книги)

Метою дослідження є порівняти архетипні системи українських, польських, кельтських і англосаксонських загадок періоду раннього християнства. Основний акцент робиться на порівнянні українських і староанглійських загадок

Scour-Resilient Bio-Inspired Geomorphic Designs: the Male Japanese Puffer Fish Nest

In 1995, divers noticed a strange circular pattern on the seabed off Japan. The geometric formations mysteriously appeared and dissolved, and no-one knew what made them. Finally, the creator of these remarkable formations was found: a new species of pufferfish from the genus Torquigener. The male puffer fish executes a design of mathematical perfection in the form of ornate circles. As he swims along the seabed, he laboriously flaps his fins and rearranges the sand, creating the geomorphic feature dubbed crop circle by the pioneers who first noticed them. The significance to understand the puffer fish design is magnified when we consider that the nest is able to maintain its morphological features for long periods even though it is built entirely of mobile particles in an area where the flow does not stop. As a relatively new discovery, the exact reasons behind why the pufferfish spends such a long time constructing and cultivating the nest it still a question that is shrouded in a substantial amount of mystery. Male puffer fish spend many days caring for the eggs, the only puffer fish genus to be overserved doing so; suggesting that Torquigener place an unusually large emphasis on ensuring the survival of their eggs. It is hypothesised that the nest is created as a mating display, as female puffer fish will visit the site, presumably assessing various characteristics of the nest. It is not known exactly what parameters the females judge the nest on; whether it be size, symmetric properties or decorative choice. However, due to some basic hydrodynamic experiments performed by Hiroshi Kawase, there is some evidence to suggest that there may be more to building the nest than solely attracting a mate. Several questions therefore arise regarding the nest. Is there an evolutionary reason that male puffer fish build these nests? Which characteristics of a nest make it attractive to female puffer fish? Are the eggs safer in a nest, perhaps from incoming currents? How exactly does fluid flow through nest, and can it be replicated and simulated? This project begins to tackle these questions through a numerical investigation (CFD) of the fluid flow through the nest in order to identify key fluid dynamic features, which may play a significant role in egg incubation and spawning using Star CCM+

The biological effects of subacute inhalation of diesel exhaust following addition of cerium oxide nanoparticles in atherosclerosis-prone mice

AbstractBackgroundCerium oxide (CeO2) nanoparticles improve the burning efficiency of fuel, however, little is known about health impacts of altered emissions from the vehicles.MethodsAtherosclerosis-prone apolipoprotein E knockout (ApoE−/−) mice were exposed by inhalation to diluted exhaust (1.7mg/m3, 20, 60 or 180min, 5 day/week, for 4 weeks), from an engine using standard diesel fuel (DE) or the same diesel fuel containing 9ppm cerium oxide nanoparticles (DCeE). Changes in hematological indices, clinical chemistry, atherosclerotic burden, tissue levels of inflammatory cytokines and pathology of the major organs were assessed.ResultsAddition of CeO2 to fuel resulted in a reduction of the number (30%) and surface area (10%) of the particles in the exhaust, whereas the gaseous co-pollutants were increased (6–8%). There was, however, a trend towards an increased size and complexity of the atherosclerotic plaques following DE exposure, which was not evident in the DCeE group. There were no clear signs of altered hematological or pathological changes induced by either treatment. However, levels of proinflammatory cytokines were modulated in a brain region and liver following DCeE exposure.ConclusionsThese results imply that addition of CeO2 nanoparticles to fuel decreases the number of particles in exhaust and may reduce atherosclerotic burden associated with exposure to standard diesel fuel. From the extensive assessment of biological parameters performed, the only concerning effect of cerium addition was a slightly raised level of cytokines in a region of the central nervous system. Overall, the use of cerium as a fuel additive may be a potentially useful way to limit the health effects of vehicle exhaust. However, further testing is required to ensure that such an approach is not associated with a chronic inflammatory response which may eventually cause long-term health effects

Mechanisms Underlying Tumor Suppressive Properties of Melatonin

There is considerable evidence that melatonin may be of use in the prevention and treatment of cancer. This manuscript will review some of the human, animal and cellular studies that provide evidence that melatonin has oncostatic properties. Confirmation that melatonin mitigates pathogenesis of cancer will be described from both direct study of its effects on carcinogenesis, and from indirect findings implicating disruption of the circadian cycle. A distinction is made between the role of melatonin in preventing the initiation of the tumorigenic pathway and the ability of melatonin to retard the progression of cancer. Melatonin appears to slow down the rate of advancement of established tumors and there is evidence that it constitutes a valuable complement to standard pharmacological and radiation treatment modalities. There are instances of the beneficial outcomes in cancer treatment which utilize a range of hormones and vitamins, melatonin being among the constituents of the mix. While these complex blends are empirically promising, they are only briefly mentioned here in view of the confounding influence of a multiplicity of agents studied simultaneously. The last section of this review examines the molecular mechanisms that potentially underlie the oncostatic effects of melatonin. Alterations in gene expression following activation of various transcription factors, are likely to be an important mediating event. These changes in gene activity not only relate to cancer but also to the aging process which underlies the onset of most tumors. In addition, epigenetic events such as modulation of histone acetylation and DNA methylation patterns throughout the lifespan of organisms need to be considered. The antioxidant and immunoregulatory roles of melatonin may also contribute to its cancer modulatory properties. Naturally, these mechanisms overlap and interact extensively. Nevertheless, in the interest of clarity and ease of reading, each is discussed as a separate topic section. The report ends with some general conclusions concerning the clinical value of melatonin which has been rather overlooked and understudied

Melatonin and Regulation of Immune Function: Impact on Numerous Diseases.

Melatonin is well known as a neuroendocrine hormone that promotes sleep. However, the many other attributes of melatonin are less apparent and not as widely appreciated. The purpose of this review is to summarize the qualities of melatonin relating to immune function. The relevance of melatonin in partially or wholly restoring optimal function, in a series of disorders related to immune dysfunction, is addressed in this report. This includes the potential relief of both autoimmune diseases and many other ailments involving abnormal immune responses, including the overall diminished effectiveness of body defenses occurring with aging. Disease states affecting a wide range of organ systems have been reported as benefitting from melatonin administration and are discussed here. A separate section addresses the potential role of melatonin in the mitigation of age-related neurological diseases, in view of the increasing importance of this area. The likely mechanistic basis of the properties by which melatonin may confer protection by its acting on immune function is also described