Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.

Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required

Advances in Understanding Environmental Risks of Red Mud After the Ajka Spill, Hungary

In the 5 years since the 2010 Ajka red mud spill (Hungary), there have been 46 scientific studies assessing the key risks and impacts associated with the largest single release of bauxite-processing residue (red mud) to the environment. These studies have provided insight into the main environmental concerns, as well as the effectiveness of remedial efforts that can inform future management of red mud elsewhere. The key immediate risks after the spill were associated with the highly caustic nature of the red mud slurry and fine particle size, which once desiccated, could generate fugitive dust. Studies on affected populations showed no major hazards identified beyond caustic exposure, while red mud dust risks were considered equal to or lesser than those provided by urban dusts of similar particle size distribution. The longer-term environmental risks were related to the saline nature of the spill material (salinization of inundated soils) and the release and the potential cycling of oxyanion-forming metals and metalloids (e.g., Al, As, Cr, Mo, and V) in the soil–water environment. Of these, those that are soluble at high pH, inefficiently removed from solution during dilution and likely to be exchangeable at ambient pH are of chief concern (e.g., Mo and V). Various ecotoxicological studies have identified negative impacts of red mud-amended soils and sediments at high volumes (typically [5 %) on different test organisms, with some evidence of molecularlevel impacts at high dose (e.g., genotoxic effects on plants and mice). These data provide a valuable database to inform future toxicological studies for red mud. However, extensive management efforts in the aftermath of the spill greatly limited these exposure risks through leachate neutralization and red mud recovery from the affected land. Monitoring of affected soils, stream sediments, waters and aquatic biota (fungi, invertebrates and fish) have all shown a very rapid recovery toward prespill conditions. The accident also prompted research that has also highlighted potential benefits of red mud use for critical raw material recovery (e.g., Ga, Co, V, rare earths, inform), carbon sequestration, biofuel crop production, and use as a soil ameliorant

Effect of oat bran on time to exhaustion, glycogen content and serum cytokine profile following exhaustive exercise

The aim of this study was to evaluate the effect of oat bran supplementation on time to exhaustion, glycogen stores and cytokines in rats submitted to training. The animals were divided into 3 groups: sedentary control group (C), an exercise group that received a control chow (EX) and an exercise group that received a chow supplemented with oat bran (EX-O). Exercised groups were submitted to an eight weeks swimming training protocol. In the last training session, the animals performed exercise to exhaustion, (e.g. incapable to continue the exercise). After the euthanasia of the animals, blood, muscle and hepatic tissue were collected. Plasma cytokines and corticosterone were evaluated. Glycogen concentrations was measured in the soleus and gastrocnemius muscles, and liver. Glycogen synthetase-α gene expression was evaluated in the soleus muscle. Statistical analysis was performed using a factorial ANOVA. Time to exhaustion of the EX-O group was 20% higher (515 ± 3 minutes) when compared with EX group (425 ± 3 minutes) (p = 0.034). For hepatic glycogen, the EX-O group had a 67% higher concentrations when compared with EX (p = 0.022). In the soleus muscle, EX-O group presented a 59.4% higher glycogen concentrations when compared with EX group (p = 0.021). TNF-α was decreased, IL-6, IL-10 and corticosterone increased after exercise, and EX-O presented lower levels of IL-6, IL-10 and corticosterone levels in comparison with EX group. It was concluded that the chow rich in oat bran increase muscle and hepatic glycogen concentrations. The higher glycogen storage may improve endurance performance during training and competitions, and a lower post-exercise inflammatory response can accelerate recovery

Scavenger receptors and β-glucan receptors participate in the recognition of yeasts by murine macrophages

Objectives: Numerous receptors have been implicated in recognition of pathogenic fungi by macrophages, including the $\beta$-glucan receptor dectin-1. The role of scavenger receptors (SRs) in anti-fungal immunity is not well characterized. Methods: We studied uptake of unopsonized Saccharomycetes cerevisiae (zymosan) and live Candida albicans yeasts as well as zymosan-stimulated $H_2O_2$ production in J774 macrophage-like cells and peritoneal exudate macrophages (PEMs). The role of different receptors was assessed with the use of competitive ligands, transfected cells and receptor-deficient macrophages. Results: The uptake of zymosan by untreated J774 cells was mediated approximately half by SRs and half by a $\beta$-glucan receptor which was distinct from dectin-1 and not linked to stimulation of $H_2O_2$ production. Ligands of $\beta$-glucan receptors and of SRs also inhibited uptake of C. albicans by macrophages (J774 cells and PEMs). In macrophages pretreated with a CpG motif-containing oligodeoxynucleotide (CpG-ODN) the relative contribution of SRs to yeast uptake increased and that of $\beta$-glucan receptors decreased. Whereas the class A SR MARCO participated in the uptake of both zymosan and C. albicans by CpG-ODN-pretreated, but not untreated macrophages, the related receptor SR-A/CD204 was involved in the uptake of zymosan, but not of C. albicans. The reduction of zymosan-stimulated $H_2O_2$ production observed in DS-pretreated J774 cells and in class A SRs-deficient PEMs suggest that class A SRs mediate part of this process. Conclusions: Our results revealed that SRs belong to a redundant system of receptors for yeasts. Binding of yeasts to different receptors in resting versus CpG-ODN-pre-exposed macrophages may differentially affect polarization of adaptive immune responses

Assessing the role of bed sediments in the persistence of red mud pollution in a shallow lake (Kinghorn Loch, UK)

Red mud is a by-product of alumina production. Little is known about the long-term fate of red mud constituents in fresh waters or of the processes regulating recovery of fresh waters following pollution control. In 1983, red mud leachate was diverted away from Kinghorn Loch, UK, after many years of polluting this shallow and monomictic lake. We hypothesised that the redox-sensitive constituents of red mud leachate, phosphorus (P), arsenic (As) and vanadium (V), would persist in the Kinghorn Loch for many years following pollution control as a result of cycling between the lake bed sediment and the overlying water column. To test this hypothesis, we conducted a 12-month field campaign in Kinghorn Loch between May 2012 and April 2013 to quantify the seasonal cycling of P, As, and V in relation to environmental conditions (e.g., dissolved oxygen (DO) concentration, pH, redox chemistry and temperature) in the lake surface and bottom waters. To confirm the mechanisms for P, As and V release, a sediment core incubation experiment was conducted using lake sediment sampled in July 2012, in which DO concentrations were manipulated to create either oxic or anoxic conditions similar to the bed conditions found in the lake. The effects on P, As, and V concentrations and species in the water column were measured daily over an eight-day incubation period. Phosphate (PO4-P) and dissolved As concentrations were significantly higher in the bottom waters (75.9 ± 30.2 μg L−1 and 23.5 ± 1.83 μg L−1, respectively) than in the surface waters (12.9 ± 1.50 μg L−1 and 14.1 ± 2.20 μg L−1, respectively) in Kinghorn Loch. Sediment release of As and P under anoxic conditions was confirmed by the incubation experiment and by the significant negative correlations between DO and P and As concentrations in the bottom waters of the lake. In contrast, the highest dissolved V concentrations occurred in the bottom waters of Kinghorn Loch under oxic conditions (15.0 ± 3.35 μg L−1), with the release from the bed sediment apparently being controlled by a combination of competitive ion concentrations, pH and redox conditions

Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail complement C3 (a critical opsonin) deposition. This results in diminished activation of phagocytes and clearance of GAS that may lead to the host being unable to limit the infection. Herein we describe the course of GAS infection in three human complement inhibitor transgenic (tg) mouse models that examined each inhibitor (human C4BP or FH) alone, or the two inhibitors together (C4BPxFH or 'double' tg). GAS infection with strains that bound C4BP and FH resulted in enhanced mortality in each of the three transgenic mouse models compared to infection in wild type mice. In addition, GAS manifested increased virulence in C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory cytokines and they died earlier than single transgenic or wt controls. The effects of hu-C4BP and hu-FH were specific for GAS strains that bound these inhibitors because strains that did not bind the inhibitors showed reduced virulence in the 'double' tg mice compared to strains that did bind; mortality was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our findings emphasize the importance of binding of complement inhibitors to GAS that results in impaired opsonization and phagocytic killing, which translates to enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg model may prove invaluable in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy

Impact of selected chemical substances on the degradation of the polyolefin materials

Zwiększająca się produkcja i konsumpcja różnego rodzaju produktów z tworzyw sztucznych prowadzi do zwiększenia strumienia odpadów, w którym przeważającą część stanowią odpady z grupy poliolefin. Z powodu braku podatności na hydrolizę czy dekompozycję, unieszkodliwianie większości odpadów z tworzyw sztucznych stanowi skomplikowany problem. Rosnąca ilość zużytych odpadów z tworzyw sztucznych wymusza poszukiwanie nowych, ekologicznych i bezpiecznych metod ich zagospodarowania. Tworzywa sztuczne są uznawane obecnie za główne zanieczyszczenie środowiska przyrodniczego, ale przekształcone w odpowiedni sposób mogą stanowić cenny surowiec produkcyjny. Recykling odpadowych polimerów jest jednym z perspektywicznych kierunków ich wykorzystania, prowadząc jednocześnie do ograniczenia zużycia surowców naturalnych. Przy kontakcie z gazami, cieczami i ciałami stałymi, substancje chemiczne mogą wnikać do wnętrza tworzywa sztucznego lub wypłukiwać z niego różne składniki. Odporność tworzywa sztucznego na wpływ substancji chemicznych określa się mianem odporności lub podatności chemicznej. Oddziaływanie substancji chemicznych na tworzywa sztuczne zależny od wielu czynników. W artykule zaprezentowano wyniki badań określające stopień odporności na degradację tworzyw poliolefinowych z zastosowaniem nieorganicznych substancji chemicznych. Stopień degradacji badanych odpadów określono poprzez rejestrację zmiany masy oraz zmian makroskopowych i mikroskopowych ich struktury.An increased production and consumption of various types of plastics leads to the increase of the wastes. The majority of wastes are formed by wastes from polyolefin group. Due to lack of susceptibility to hydrolysis or decomposition, utilization of the plastic wastes is a very complicated problem. Increasing amount of plastic wastes forces a search for the new, ecological and safe methods of waste management. Nowadays, plastics are considered to be main pollution of the natural environment. However, modified plastics can constitute a valuable production material. Recycling of waste polymers is one of the far-reaching methods of their utilization and at the same time limits the consumption of the natural resources. When having contacts with gases, liquids and solids, chemical substances may penetrate into the plastic or wash out various components from them. Resistance of plastics to the impact of chemical substances is called chemical resistance or susceptibility. Impact of chemical substances on plastics depends on many factors. The article will present research results which will define the grade of resistance to degradation of polyolefin materials with the use of non-organic chemical substances. The degree of degradation of the waste tests has been defined through the registration of the weight change as well as macroscopic and microscopic changes of their structure