Reactive oxygen species regulate caspase-11 expression and activation of the non-canonical NLRP3 inflammasome during enteric pathogen infection

Enteropathogenic and enterohemorrhagic bacterial infections in humans are a severe cause of morbidity and mortality. Although NOD-like receptors (NLRs) NOD2 and NLRP3 have important roles in the generation of protective immune responses to enteric pathogens, whether there is crosstalk among NLRs to regulate immune signaling is not known. Here, we show that mice and macrophages deficient in NOD2, or the downstream adaptor RIP2, have enhanced NLRP3-and caspases-11-dependent non-canonical inflammasome activation in a mouse model of enteropathogenic Citrobacter rodentium infection. Mechanistically, NOD2 and RIP2 regulate reactive oxygen species (ROS) production. Increased ROS in Rip2-deficient macrophages subsequently enhances c-Jun N-terminal kinase (JNK) signaling resulting in increased caspase-11 expression and activation, and more non-canonical NLRP3-dependant inflammasome activation. Intriguingly, this leads to protection of the colon epithelium for up to 10 days in Rip2-deficient mice infected with C. rodentium. Our findings designate NOD2 and RIP2 as key regulators of cellular ROS homeostasis and demonstrate for the first time that ROS regulates caspase-11 expression and non-canonical NLRP3 inflammasome activation through the JNK pathway

Modeling Habitat Associations for the Common Loon (\u3cem\u3eGavia immer\u3c/em\u3e) at Multiple Scales in Northeastern North America

Common Loon (Gavia immer) is considered an emblematic and ecologically important example of aquatic-dependent wildlife in North America. The northern breeding range of Common Loon has contracted over the last century as a result of habitat degradation from human disturbance and lakeshore development. We focused on the state of New Hampshire, USA, where a long-term monitoring program conducted by the Loon Preservation Committee has been collecting biological data on Common Loon since 1976. The Common Loon population in New Hampshire is distributed throughout the state across a wide range of lake-specific habitats, water quality conditions, and levels of human disturbance. We used a multiscale approach to evaluate the association of Common Loon and breeding habitat within three natural physiographic ecoregions of New Hampshire. These multiple scales reflect Common Loon-specific extents such as territories, home ranges, and lake-landscape influences. We developed ecoregional multiscale models and compared them to single-scale models to evaluate model performance in distinguishing Common Loon breeding habitat. Based on information-theoretic criteria, there is empirical support for both multiscale and single-scale models across all three ecoregions, warranting a model-averaging approach. Our results suggest that the Common Loon responds to both ecological and anthropogenic factors at multiple scales when selecting breeding sites. These multiscale models can be used to identify and prioritize the conservation of preferred nesting habitat for Common Loon populations

Predictive and prognostic potential of liver function assessment in patients with advanced hepatocellular carcinoma: a systematic literature review

INTRODUCTION: We conducted a systematic literature review to assess the utility of liver function assessments for predicting disease prognosis and response to systemic anticancer therapy in patients with advanced hepatocellular carcinoma (aHCC). METHODS: This was a PRISMA-standard review and was registered with PROSPERO (CRD42021244588). MEDLINE and Embase were systematically searched (March 24, 2021) to identify publications reporting the efficacy and/or safety of systemic anticancer therapy (vs any/no comparator) in liver-function-defined subgroups in phase 2 or 3 aHCC trials. Screening was completed by a single reviewer, with uncertainties resolved by a second reviewer and/or the authors. English-language full-text articles and congress abstracts were eligible for inclusion. Included publications were described and assessed for risk of bias using the GRADE methodology. RESULTS: Twenty (of 2579) screened publications were eligible; seven categorised liver function using the albumin–bilirubin system, nine using the Child–Pugh system, four using both. GRADE assessment classified ten, nine, and one publication(s) as reporting moderate-quality, low-quality, and very-low-quality evidence, respectively. Analyses of cross-trial trends of within-exposure arm analyses (active and control) reported a positive relationship between baseline liver function and overall survival and progression-free survival, supporting liver function as a prognostic marker in aHCC. There were also signals for a modest relationship between more preserved baseline liver function and extent of systemic treatment benefit, and with more preserved liver function and lower incidence of safety events. CONCLUSION: This review supports liver function as a prognostic variable in aHCC, and highlights the value of a priori stratification of patients by baseline liver function in aHCC trials. The predictive value of liver function warrants further study. Findings were limited by the quality of available data

Optimizing the vertebrate vestibular semicircular canal: could we balance any better?

The fluid-filled semicircular canals (SCCs) of the vestibular system are used by all vertebrates to sense angular rotation. Despite masses spanning seven decades, all mammalian SCCs are nearly the same size. We propose that the SCC represents a sensory organ that evolution has `optimally designed'. Four geometric parameters are used to characterize the SCC, and `building materials' of given physical properties are assumed. Identifying physical and physiological constraints on SCC operation, we find that the most sensitive SCC has dimensions consistent with available data.Comment: 4 pages, 3 figure

Reclaiming the Shiawassee Flats: Monitoring During Hydrologic Restoration of the Shiawassee Flats Ecosystem

In 2016, the US Fish and Wildlife Service (USFWS) completed the restoration of two new wetland units: Maankiki North (MN, opened in 2017) and Maankiki South (MS, opened in 2018) at the Shiawassee National Wildlife Refuge near Saginaw, Michigan. The Refuge sought to reconnect these units, formerly farmland, to the dynamic hydrology of the Shiawassee River, mimicking the function of this area’s historic floodplain complex. In early 2019, staff at the Shiawassee National Wildlife Refuge asked for support from students attending the University of Michigan School for Environment and Sustainability (SEAS) to aid in post-restoration monitoring of the biological conditions in the recently restored Maankiki units and Pool 1A, a wetland unit hydrologically reconnected to the Shiawassee River in 1958. Sampling in 2019 would complement pre-restoration research previously done by UM groups. Sampling techniques were modeled after the Great Lakes Coastal Wetland Monitoring Program and were used to create protocols to guide future studies. This report, organized by the abiotic and biotic factors investigated, represents the culmination of our team’s research. Water Quality describes the chemical, physical, and biological parameters used to measure the tolerance of the wetland units’ biological communities. ● Water quality varies by month, distance from the water control structure, vegetation type, and unit. ● Dissolved oxygen decreased throughout the season to levels unsafe for fish, likely due to warming temperatures. ● In the future, water quality monitoring should more closely reflect the GLCWMP methods, focus on nutrient testing, and more data collection from the Shiawassee River and Spaulding Drain. Vegetation identifies and compares the plant communities within and among wetland units and uses their diversity and abundance to evaluate wetland health. ● Calculations of importance values and dissimilarity indices show decreasing diversity from Maankiki South to Pool 1A to Maankiki North, which has a high abundance and density of invasive Typha. ● The Floristic Quality Assessment and Index of Biotic Integrity scored Maankiki South as ‘Medium Quality.’ Degradation increased from MS to Pool 1A to MN. ● Future research recommendations include the continued implementation of our monitoring protocol, managing the units’ flood duration and frequency to mimic the natural flow regime, and the harvesting of Typha biomass. Macroinvertebrates catalogs and compares indicator insect families in response to each unit’s water quality, vegetation types, and monthly variation. ● Communities changed throughout the summer following standard life-cycle trends. ● The majority of families found are known to be tolerant to the water quality conditions common to wetlands, such as high turbidity and low DO. ● Future management recommendations include the continued implementation of our monitoring protocol, the use of an elutriator while sampling, identifying individuals to genera, and more closely and accurately categorizing the unit’s substrates. Fish details the different gear types utilized to measure and compare the abundance, composition, and structure of fish communities and the environmental factors shaping these traits within and among units. ● Fish sampling included the use of multiple frame- and mesh-size fyke nets, gill nets, and electrofishing. ● The fish community contained no sensitive species. We found a mix of riverine and wetland species, in addition to abundant juvenile fish, that indicate the wetland units are used for spawning and refuge by species from both ecosystems. ● Future management recommendations include continued monitoring with multiple methods, tailoring methods to target species, and using minnow traps to catch smaller species and juveniles. We recommend continuous monitoring that incorporates the Shiawassee River and Spaulding Drain to understand how biological communities in the river are using the wetland units, and to provide a comparison of ecological function of restored wetlands to the river. Past, present, and future studies should be analyzed in combination to assist the Refuge in making science-based management decisions.Master of ScienceSchool for Environment and SustainabilityUniversity of Michiganhttps://deepblue.lib.umich.edu/bitstream/2027.42/154780/1/371_Shiawassee Flats_Final_Doc.pd

Towards a new generation axion helioscope

We study the feasibility of a new generation axion helioscope, the most ambitious and promising detector of solar axions to date. We show that large improvements in magnetic field volume, x-ray focusing optics and detector backgrounds are possible beyond those achieved in the CERN Axion Solar Telescope (CAST). For hadronic models, a sensitivity to the axion-photon coupling of \gagamma\gtrsim {\rm few} \times 10^{-12} GeV$^{-1}$ is conceivable, 1--1.5 orders of magnitude beyond the CAST sensitivity. If axions also couple to electrons, the Sun produces a larger flux for the same value of the Peccei-Quinn scale, allowing one to probe a broader class of models. Except for the axion dark matter searches, this experiment will be the most sensitive axion search ever, reaching or surpassing the stringent bounds from SN1987A and possibly testing the axion interpretation of anomalous white-dwarf cooling that predicts $m_a$ of a few meV. Beyond axions, this new instrument will probe entirely unexplored ranges of parameters for a large variety of axion-like particles (ALPs) and other novel excitations at the low-energy frontier of elementary particle physics.Comment: 37 pages, 11 figures, accepted for publication in JCA

Sediment structure and physicochemical changes following tidal inundation at a large open coast managed realignment site

Managed realignment (MR) schemes are being implemented to compensate for the loss of intertidal saltmarsh habitats by breaching flood defences and inundating the formerly defended coastal hinterland. However, studies have shown that MR sites have lower biodiversity than anticipated, which has been linked with anoxia and poor drainage resulting from compaction and the collapse of sediment pore space caused by the site's former terrestrial land use. Despite this proposed link between biodiversity and soil structure, the evolution of the sediment sub-surface following site inundation has rarely been examined, particularly over the early stages of the terrestrial to marine or estuarine transition. This paper presents a novel combination of broad- and intensive-scale analysis of the sub-surface evolution of the Medmerry Managed Realignment Site (West Sussex, UK) in the three years following site inundation. Repeated broad-scale sediment physiochemical datasets are analysed to assess the early changes in the sediment subsurface and the preservation of the former terrestrial surface, comparing four locations of different former land uses. Additionally, for two of these locations, high-intensity 3D-computed X-ray microtomography and Itrax micro-X-ray fluorescence spectrometry analyses are presented. Results provide new data on differences in sediment properties and structure related to the former land use, indicating that increased agricultural activity leads to increased compaction and reduced porosity. The presence of anoxic conditions, indicative of poor hydrological connectivity between the terrestrial and post-inundation intertidal sediment facies, was only detected at one site. This site has experienced the highest rate of accretion over the terrestrial surface (ca. 7 cm over 36 months), suggesting that poor drainage is caused by the interaction (or lack of) between sediment facies rather than the former land use. This has significant implications for the design of future MR sites in terms of preparing sites, their anticipated evolution, and the delivery of ecosystem services

The International Axion Observatory (IAXO)

The International Axion Observatory (IAXO) is a new generation axion helioscope aiming at a sensitivity to the axion-photon coupling of a few 10$^{12}$ GeV$^{-1}$, i.e. 1 - 1.5 orders of magnitude beyond the one currently achieved by CAST. The project relies on improvements in magnetic field volume together with extensive use of x-ray focusing optics and low background detectors, innovations already successfully tested in CAST. Additional physics cases of IAXO could include the detection of electron-coupled axions invoked to solve the white dwarfs anomaly, relic axions, and a large variety of more generic axion-like particles (ALPs) and other novel excitations at the low-energy frontier of elementary particle physics. This contribution is a summary of our paper [1] to which we refer for further details.Comment: 4 pages, 2 figures. To appear in the proceedings of the 7th Patras Workshop on Axions, WIMPs and WISPs, Mykonos, Greece, 201

Sticky Dead Microbes: rapid abiotic retention of microbial necromass in soil

Microbial necromass dominates soil organic matter. Recent research on necromass and soil carbon storage has focused on necromass production and stabilization mechanisms but not on the mechanisms of necromass retention. We present evidence from soil incubations with stable-isotope labeled necromass that abiotic adsorption may be more important than biotic immobilization for short-term necromass retention. We demonstrate that necromass adsorbs not only to mineral surfaces, but may also interact with other necromass. Furthermore, necromass cell chemistry alters necromass-necromass interaction, with more bacterial tracer retained when there is yeast necromass present. These findings suggest that the adsorption and abiotic interaction of microbial necromass and its functional properties, beyond chemical stability, deserve further investigation in the context of soil carbon sequestration