MyD88 oligomer size functions as a physical threshold to trigger IL1R Myddosome signaling

A recurring feature of innate immune receptor signaling is the self-assembly of signaling proteins into oligomeric complexes. The Myddosome is an oligomeric complex that is required to transmit inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for how Myddosome proteins self-assemble and regulate intracellular signaling remains poorly understood. Here, we developed a novel assay to analyze the spatiotemporal dynamics of IL1R and Myddosome signaling in live cells. We found that MyD88 oligomerization is inducible and initially reversible. Moreover, the formation of larger, stable oligomers consisting of more than four MyD88s triggers the sequential recruitment of IRAK4 and IRAK1. Notably, genetic knockout of IRAK4 enhanced MyD88 oligomerization, indicating that IRAK4 controls MyD88 oligomer size and growth. MyD88 oligomer size thus functions as a physical threshold to trigger downstream signaling. These results provide a mechanistic basis for how protein oligomerization might function in cell signaling pathways.     

In vitro cell growth of marine archaeal-bacterial consortia during anaerobic oxidation of methane with sulfate

Anoxic sediment from a methane hydrate area (Hydrate Ridge, north-east Pacific; water depth 780 m) was incubated in a long-term laboratory experiment with semi-continuous supply of pressurized [1.4 MPa (14 atm)] methane and sulfate to attempt in vitro propagation of the indigenous consortia of archaea (ANME-2) and bacteria (DSS, Desulfosarcina/Desulfococcus cluster) to which anaerobic oxidation of methane (AOM) with sulfate has been attributed. During 24 months of incubation, the rate of AOM (measured as methane-dependent sulfide formation) increased from 20 to 230 micromol day(-1) (g sediment dry weight)(-1) and the number of aggregates (determined by microscopic counts) from 0.5 x 10(8) to 5.7 x 10(8) (g sediment dry weight)(-1). Fluorescence in situ hybridization targeting 16S rRNA of both partners showed that the newly grown consortia contained central archaeal clusters and peripheral bacterial layers, both with the same morphology and phylogenetic affiliation as in the original sediment. The development of the AOM rate and the total consortia biovolume over time indicated that the consortia grew with a doubling time of approximately 7 months (growth rate 0.003 day(-1)) under the given conditions. The molar growth yield of AOM was approximately 0.6 g cell dry weight (mol CH(4) oxidized)(-1); according to this, only 1% of the consumed methane is channelled into synthesis of consortia biomass. Concentrations of biomarker lipids previously attributed to ANME-2 archaea (e.g. sn-2-hydroxyarchaeol, archaeol, crocetane, pentamethylicosatriene) and Desulfosarcina-like bacteria [e.g. hexadecenoic-11 acid (16:1omega5c), 11,12-methylene-hexadecanoic acid (cy17:0omega5,6)] strongly increased over time (some of them over-proportionally to consortia biovolume), suggesting that they are useful biomarkers to detect active anaerobic methanotrophic consortia in sediments.     

Selective mortality of a coral reef damselfish: role of predator–competitor synergisms

Phenotypic variability within cohorts of juvenile organisms can serve as the basis for selective mortality. Previous studies have demonstrated the important role that predators play in this process but not the impact of competitors on selective predation. We use a combination of lab and field studies to evaluate the effect of the presence of adult competitor damselfish (Dascyllus aruanus and Pomacentrus moluccensis; family Pomacentridae) on the selective mortality of newly-arrived (settled) lemon damselfish (P. moluccensis) by resident predator fishes (Pseudochromis fuscus Pseudochromidae and Cheilodipterus quinquelineatus Apogonidae). Lab trials consisted of mesocosm experiments in which the behaviour, mortality, and physiological condition (measured as lipid content) of surviving P. moluccensis settlers from each of three treatments: (1) predators absent, (2) predators present, and (3) predators and competitors present, were compared. The field study involved stocking newly settled P. moluccensis on natural bommies (patch reefs) which had either been subject to a partial removal of resident fish (predators and competitors) or left alone. Results indicated there was very strong condition-based selective mortality in both the lab and field trials. In both cases there was a strong positive relationship between mortality and the lipid content of surviving fish; implying low-condition fish were selectively removed. The mesocosm trials indicated that the strength of mortality as well as condition selectivity was higher when competitors were present than when they were absent. Behavioural observations in the mesocosm study suggest that attention by juvenile P. moluccensis to the movements and occasional chases of the competitors (especially D. aruanus) reduced their vigilance to the predators. These results suggest the important and interactive roles which condition of newly settled reef fish and interspecific competition can play in the outcomes of post-settlement predation. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

De novo synthesis of 3'-nucleotidase in germinating wheat embryo

The enzyme 3′-AMP nucleotidase was purified 2,500- to 5,000-fold from extracts of an acetone powder of wheat (Triticum aestivum) embryonic axes germinated for 40 hours. Sodium dodecyl sulfate acrylamide gel electrophoresis and chromatography on Biogel-P100 indicate that the enzyme is monomeric with a molecular weight of 39,000. Extracts of embryos germinated up to 6 hours have only 1% of the 40-hour level of enzyme activity. To see if the increase to 40 hours represents de novo synthesis, extracts were compared for their ability to react with a rabbit antibody prepared against the enzyme. In immunodiffusion tests, 40-hour extracts showed a strong precipitin line coincident with that of the purified enzyme, whereas no precipitation was observed with 1-hour extracts. When the enzyme present in 40-hour extracts was partially inactivated by EDTA, it still blocked the ability of the antibody to inhibit enzyme activity. Extracts of 1-hour embryos, in contrast, were not able to block the inhibitory activity of the antibody. Embryos allowed to take up ³⁵SO₄ between 40 and 46 hours of germination synthesized ³⁵S-labeled 3′-nucleotidase. In contrast, no radioactive protein synthesized by embryos during the first 6 hours of germination coincided on gel electrophoresis with the enzyme. These results indicate that the increase in 3′-nucleotidase activity is a consequence of de novo synthesis of the enzyme.     

Assessing the response of forest productivity to climate extremes in Switzerland using model–data fusion

The response of forest productivity to climate extremes strongly depends on ambient environmental and site conditions. To better understand these relationships at a regional scale, we used nearly 800 observation years from 271 permanent long‐term forest monitoring plots across Switzerland, obtained between 1980 and 2017. We assimilated these data into the 3‐PG forest ecosystem model using Bayesian inference, reducing the bias of model predictions from 14% to 5% for forest stem carbon stocks and from 45% to 9% for stem carbon stock changes. We then estimated the productivity of forests dominated by Picea abies and Fagus sylvatica for the period of 1960–2018, and tested for productivity shifts in response to climate along elevational gradient and in extreme years. Simulated net primary productivity (NPP) decreased with elevation (2.86 ± 0.006 Mg C ha^?1 year^?1 km^?1 for P. abies and 0.93 ± 0.010 Mg C ha^?1 year^?1 km^?1 for F. sylvatica). During warm–dry extremes, simulated NPP for both species increased at higher and decreased at lower elevations, with reductions in NPP of more than 25% for up to 21% of the potential species distribution range in Switzerland. Reduced plant water availability had a stronger effect on NPP than temperature during warm‐dry extremes. Importantly, cold–dry extremes had negative impacts on regional forest NPP comparable to warm–dry extremes. Overall, our calibrated model suggests that the response of forest productivity to climate extremes is more complex than simple shift toward higher elevation. Such robust estimates of NPP are key for increasing our understanding of forests ecosystems carbon dynamics under climate extremes.     

Perspectives in PDK1 evolution: Insights from photosynthetic and non-photosynthetic organisms

Protein kinases belonging to the AGC group modulate many diverse cellular processes in all eukaryotes. One important way to regulate AGC kinases is through phosphorylation by the upstream kinase PDK1. PDK1 localization and activity usually depend on interactions with phospholipids, which are mediated by a conserved lipid-binding pleckstrin homology (PH) domain. We recently analyzed putative PDK1 sequences from 17 photosynthetic organisms, finding that PDK1s from vascular and nonvascular species seem to be distinguished by the presence or absence of a PH domain, respectively. The only other reported PDK1 lacking a PH domain is from yeast (Saccharomyces cerevisiae). These observations raise questions about how plant PDK1s and their lipid-binding capabilities have evolved in relation to other eukaryotes, and what this means for PDK1 function. Here we use 100 PDK1 sequences from diverse organisms to discuss possible evolutionary aspects of plant PDK1 structure and lipid binding.     

Interrogating the neo-pluralist orthodoxy in American anthropology

For most of the twentieth century the state was not a major part of the anthropological toolkit. Despite significant archaeologically driven work on evolution and state formation, most socio-cultural anthropologists have viewed the state with empiricist scepticism, populist hostility, or ethnographic indifference. Typically, state-theory has been left to other disciplines, such as political science and sociology. Since the end of the cold war there has been a greatly increased interest in the state among anthropologists. Philip Abrams, Michael Herzfeld, and Akhil Gupta, who coined the phrase “ethnography of the state”, have been particularly important to this development. However, there remains no serious engagement with the body of state-theory generated, over the last century, by political activists, scientists, sociologists, and anthropologists. It will be argued that this has allowed for the growth of an unproblematised orthodoxy around an ethnographically informed variant of classic American pluralist state-theory. This orthodoxy has hobbled the understanding and explanation of complex political phenomena, led to confusion between hypotheses and conclusions, and tied parts of the discipline to a partisan political project that remains largely un-interrogated. This essay seeks to provide context and clarification on state-theory as a step towards discussion of anthropology’s contemporary engagement with the state and broader questions of political action and social change.     

Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials

Introduction  

The efficacy and the optimal type and volume of aerobic exercise (AE) in fibromyalgia syndrome (FMS) are not established. We therefore assessed the efficacy of different types and volumes of AE in FMS.