SOCS2 Influences LPS Induced Human Monocyte-Derived Dendritic Cell Maturation

Dendritic cells (DCs) are highly specific antigen presenting cells, which link innate and adaptive immune responses and participate in protecting hosts from invading pathogens. DCs can be generated in vitro by culturing human monocytes with GM-CSF and IL-4 followed by LPS induced DC maturation. We set out to study the suppressor of cytokine signaling (SOCS) proteins during maturation and activation of human monocyte-derived DCs from peripheral blood in vitro. We found that the expression of SOCS2 mRNA and protein is dramatically up-regulated during DC maturation. Silencing of SOCS2 using siRNA, inhibited DC maturation as evidenced by a decreased expression of maturation markers such as CD83, co-stimulatory molecules CD40, CD86 and HLA-DR. Furthermore, silencing of SOCS2 decreased LPS induced activation of MAP kinases (SAKP/JNK, p38, ERK), IRF3, decreased the translocation of the NF-κB transcription factor and reduced downstream gene mRNA expression. These results suggest a role for SOCS2 in the MyD88-dependent and -independent TLR4 signaling pathways. In conclusion, our results demonstrate that SOCS2 is required for appropriate TLR4 signaling in maturating human DCs via both the MyD88-dependent and -independent signaling pathway

LPS Regulates SOCS2 Transcription in a Type I Interferon Dependent Autocrine-Paracrine Loop

Recent studies suggest that SOCS2 is involved in the regulation of TLR signaling. In this study, we found that the expression of SOCS2 is regulated in human monocyte-derived DC by ligands stimulating TLR2, 3, 4, 5, 8 and 9 signaling. SOCS2 induction by LPS was dependent on the type I IFN regulated transcription factors IRF1 and IRF3 as shown by using silencing RNAs for IRFs. Blocking endogenous type I IFN signaling, by neutralizing antibodies to the receptor IFNAR2, abolished SOCS2 mRNA expression after TLR4 stimulation. Transcription factors STAT3, 5 and 6 displayed putative binding sites in the promoter regions of the human SOCS2 gene. Subsequent silencing experiments further supported that STAT3 and STAT5 are involved in LPS induced SOCS2 regulation. In mice we show that SOCS2 mRNA induction is 45% lower in bone marrow derived macrophages derived from MyD88−/− mice, and do not increase in BMMs from IRF3−/− mice after BCG infection. In conclusion, our results suggest that TLR4 signaling indirectly increases SOCS2 in late phase mainly via the production of endogenous type I IFN, and that subsequent IFN receptor signaling activates SOCS2 via STAT3 and STAT5

Methylmercury exposure in a subsistence fishing community in Lake Chapala, Mexico: an ecological approach

<p>Abstract</p> <p>Background</p> <p>Elevated concentrations of mercury have been documented in fish in Lake Chapala in central Mexico, an area that is home to a large subsistence fishing community. However, neither the extent of human mercury exposure nor its sources and routes have been elucidated.</p> <p>Methods</p> <p>Total mercury concentrations were measured in samples of fish from Lake Chapala; in sections of sediment cores from the delta of Rio Lerma, the major tributary to the lake; and in a series of suspended-particle samples collected at sites from the mouth of the Lerma to mid-Lake. A cross-sectional survey of 92 women ranging in age from 18-45 years was conducted in three communities along the Lake to investigate the relationship between fish consumption and hair mercury concentrations among women of child-bearing age.</p> <p>Results</p> <p>Highest concentrations of mercury in fish samples were found in carp (mean 0.87 ppm). Sediment data suggest a pattern of moderate ongoing contamination. Analyses of particles filtered from the water column showed highest concentrations of mercury near the mouth of the Lerma. In the human study, 27.2% of women had >1 ppm hair mercury. On multivariable analysis, carp consumption and consumption of fish purchased or captured from Lake Chapala were both associated with significantly higher mean hair mercury concentrations.</p> <p>Conclusions</p> <p>Our preliminary data indicate that, despite a moderate level of contamination in recent sediments and suspended particulate matter, carp in Lake Chapala contain mercury concentrations of concern for local fish consumers. Consumption of carp appears to contribute significantly to body burden in this population. Further studies of the consequences of prenatal exposure for child neurodevelopment are being initiated.</p

The impact of COVID-19 on the management of European protected areas and policy implications

The COVID-19 pandemic led to many European countries imposing lockdown measures and limiting people’s movement during spring 2020. During the summer 2020, these strict lockdown measures were gradually lifted while in autumn 2020, local restrictions started to be re-introduced as a second wave emerged. After initial restrictions on visitors accessing many Nature Protected Areas (PAs) in Europe, management authorities have had to introduce measures so that all users can safely visit these protected landscapes. In this paper, we examine the challenges that emerged due to COVID-19 for PAs and their deeper causes. By considering the impact on and response of 14 popular European National and Nature Parks, we propose tentative longer-term solutions going beyond the current short-term measures that have been implemented. The most important challenges identified in our study were overcrowding, a new profile of visitors, problematic behavior, and conflicts between different user groups. A number of new measures have been introduced to tackle these challenges including information campaigns, traffic management, and establishing one-way systems on trail paths. However, measures to safeguard public health are often in conflict with other PA management measures aiming to minimize disturbance of wildlife and ecosystems. We highlight three areas in which management of PAs can learn from the experience of this pandemic: managing visitor numbers in order to avoid overcrowding through careful spatial planning, introducing educational campaigns, particularly targeting a new profile of visitors, and promoting sustainable tourism models, which do not rely on large visitor numbers.European Research Council (ERC) under the European Union’s Horizon 2020 research programme (Project FIDELIO, grant agreement no. 802605)

Sarcopenia: etiology, clinical consequences, intervention, and assessment

The aging process is associated with loss of muscle mass and strength and decline in physical functioning. The term sarcopenia is primarily defined as low level of muscle mass resulting from age-related muscle loss, but its definition is often broadened to include the underlying cellular processes involved in skeletal muscle loss as well as their clinical manifestations. The underlying cellular changes involve weakening of factors promoting muscle anabolism and increased expression of inflammatory factors and other agents which contribute to skeletal muscle catabolism. At the cellular level, these molecular processes are manifested in a loss of muscle fiber cross-sectional area, loss of innervation, and adaptive changes in the proportions of slow and fast motor units in muscle tissue. Ultimately, these alterations translate to bulk changes in muscle mass, strength, and function which lead to reduced physical performance, disability, increased risk of fall-related injury, and, often, frailty. In this review, we summarize current understanding of the mechanisms underlying sarcopenia and age-related changes in muscle tissue morphology and function. We also discuss the resulting long-term outcomes in terms of loss of function, which causes increased risk of musculoskeletal injuries and other morbidities, leading to frailty and loss of independence

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Assessing the ecological impact of banana farms on water quality using aquatic macroinvertebrate community composition

In Costa Rica, considerable effort goes to conservation and protection of biodiversity, while at the same time agricultural pesticide use is among the highest in the world. Several protected areas, some being wetlands or marine reserves, are situated downstream large-scale banana farms, with an average of 57 pesticide applications per year. The banana industry is increasingly aware of the need to reduce their negative environmental impact, but few ecological field studies have been made to evaluate the efficiency of proposed mitigation strategies. This study compared the composition of benthic macroinvertebrate communities up- and downstream effluent water from banana farms in order to assess whether benthic invertebrate community structure can be used to detect environmental impact of banana farming, and thereby usable to assess improvements in management practises. Aquatic invertebrate samples were collected at 13 sites, using kick-net sampling, both up- and downstream banana farms in fast flowing streams in the Caribbean zone of Costa Rica. In total, 2888 invertebrate specimens were collected, belonging to 15 orders and 48 families or taxa. The change in community composition was analysed using multivariate statistics. Additionally, a biodiversity index and the Biological Monitoring Working Party (BMWP) score system was applied along with a number of community composition descriptors. Multivariate analyses indicated that surface waters immediately up- and downstream large-scale banana farms have different macroinvertebrate community compositions with the most evident differences being higher dominance by a single taxa and a much higher total abundance, mostly of that same taxon. Assessment of macroinvertebrate community composition thus appears to be a viable approach to detect negative impact from chemical-intensive agriculture and could become an effective means to monitor the efficacy of changes/proposed improvements in farming practises in Costa Rica and similar systems

MAGIC and Fermi-LAT gamma-ray results on unassociated HAWC sources

The HAWC Collaboration released the 2HWC catalogue of TeV sources, in which 19 show no association with any known high-energy (HE; E greater than or similar to 10 GeV) or very-high-energy (VHE; E greater than or similar to 300 GeV) sources. This catalogue motivated follow-up studies by both the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) and Fermi-LAT (Large Area Telescope) observatories with the aim of investigating gamma-ray emission over a broad energy band. In this paper, we report the results from the first joint work between High Altitude Water Cherenkov (HAWC), MAGIC, and Fermi-LAT on three unassociated HAWC sources: 2HWC J2006+341, 2HWC J1907+084*, and 2HWC J1852+013*. Although no significant detection was found in the HE and VHE regimes, this investigation shows that a minimum 1 degrees extension (at 95 per cent confidence level) and harder spectrum in the GeV than the one extrapolated from HAWC results are required in the case of 2HWC J1852+013*, whilst a simply minimum extension of 0.16 degrees (at 95 per cent confidence level) can already explain the scenario proposed by HAWC for the remaining sources. Moreover, the hypothesis that these sources are pulsar wind nebulae is also investigated in detail

Sensitivity of the Cherenkov Telescope Array to a dark matter signal from the Galactic centre

We provide an updated assessment of the power of the Cherenkov Telescope Array (CTA) to search for thermally produced dark matter at the TeV scale, via the associated gamma-ray signal from pair-annihilating dark matter particles in the region around the Galactic centre. We find that CTA will open a new window of discovery potential, significantly extending the range of robustly testable models given a standard cuspy profile of the dark matter density distribution. Importantly, even for a cored profile, the projected sensitivity of CTA will be sufficient to probe various well-motivated models of thermally produced dark matter at the TeV scale. This is due to CTA's unprecedented sensitivity, angular and energy resolutions, and the planned observational strategy. The survey of the inner Galaxy will cover a much larger region than corresponding previous observational campaigns with imaging atmospheric Cherenkov telescopes. CTA will map with unprecedented precision the large-scale diffuse emission in high-energy gamma rays, constituting a background for dark matter searches for which we adopt state-of-the-art models based on current data. Throughout our analysis, we use up-to-date event reconstruction Monte Carlo tools developed by the CTA consortium, and pay special attention to quantifying the level of instrumental systematic uncertainties, as well as background template systematic errors, required to probe thermally produced dark matter at these energies