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\"Meaning is everywhere and everybody must interpret. Nobody argued this more persuasively than Clifford Geertz. From Balinese cock fights to sheep raids to theater states, Geertz showed that there is no escape from the sticky webs of meaning that capture our lives. But what exactly is Geertz saying, and should we still listen to him? After all, many argue that his ideas have run out of steam. This book confronts Geertz and his critics, offering surprising answers from various disciplines and identifying for the first time the contours of \"the Geertz Effect.\"\"--Provided by publisher.

We present a suite of high-resolution simulations of an isolated dwarf galaxy using four different hydrodynamical codes: Gizmo, Arepo, Gadget, and Ramses. All codes adopt the same physical model, which includes radiative cooling, photoelectric heating, star formation, and supernova (SN) feedback. Individual SN explosions are directly resolved without resorting to subgrid models, eliminating one of the major uncertainties in cosmological simulations. We find reasonable agreement on the time-averaged star formation rates as well as the joint density–temperature distributions between all codes. However, the Lagrangian codes show significantly burstier star formation, larger SN-driven bubbles, and stronger galactic outflows compared to the Eulerian code. This is caused by the behavior in the dense, collapsing gas clouds when the Jeans length becomes unresolved: Gas in Lagrangian codes collapses to much higher densities than that in Eulerian codes, as the latter is stabilized by the minimal cell size. Therefore, more of the gas cloud is converted to stars and SNe are much more clustered in the Lagrangian models, amplifying their dynamical impact. The differences between Lagrangian and Eulerian codes can be reduced by adopting a higher star formation efficiency in Eulerian codes, which significantly enhances SN clustering in the latter. Adopting a zero SN delay time reduces burstiness in all codes, resulting in vanishing outflows as SN clustering is suppressed.

Interleukin-1β-induced disruption to endothelial stability and vascular permeability in a human in vitro model is shown to be independent of downstream nuclear factor-κB activation, relying instead on a MYD88–ARNO–ARF6 signalling cascade; inhibiting proteins involved in this pathway is shown to improve outcomes in animal models of inflammatory disease. New targets for anti-inflammatory intervention Cytokines, the circulating proteins that activate the immune system, also disrupt cell–cell junctions and can trigger tissue oedema and destruction. Using an in vitro human endothelial cell model, this study shows that the disruptive effects of one such cytokine, interleukin-1 β, are NF-κB independent. Instead they depend on a novel non-canonical pathway involving intracellular GTPases that regulate cadherin trafficking and cell–cell interactions. Targeting of this signalling cascade in an animal model of arthritis prevents cytokine-mediated disruption of endothelial cell barriers and limits tissue damage. The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as interleukin-1β (IL-1β), which in turn activate a well-described, myeloid-differentiation factor 88 (MYD88)-mediated, nuclear factor-κB (NF-κB)-dependent transcriptional pathway that results in inflammatory-cell activation and recruitment 1 , 2 , 3 , 4 . Endothelial cells, which usually serve as a barrier to the movement of inflammatory cells out of the blood and into tissue, are also critical mediators of the inflammatory response 5 , 6 . Paradoxically, the cytokines vital to a successful immune defence also have disruptive effects on endothelial cell–cell interactions and can trigger degradation of barrier function and dissociation of tissue architecture 7 , 8 , 9 . The mechanism of this barrier dissolution and its relationship to the canonical NF-κB pathway remain poorly defined. Here we show that the direct, immediate and disruptive effects of IL-1β on endothelial stability in a human in vitro cell model are NF-κB independent and are instead the result of signalling through the small GTPase ADP-ribosylation factor 6 (ARF6) and its activator ARF nucleotide binding site opener (ARNO; also known as CYTH2). Moreover, we show that ARNO binds directly to the adaptor protein MYD88, and thus propose MYD88–ARNO–ARF6 as a proximal IL-1β signalling pathway distinct from that mediated by NF-κB. Finally, we show that SecinH3, an inhibitor of ARF guanine nucleotide-exchange factors such as ARNO, enhances vascular stability and significantly improves outcomes in animal models of inflammatory arthritis and acute inflammation.

Traditional star formation subgrid models implemented in cosmological galaxy formation simulations, such as that of V. Springel & L. Hernquist (hereafter SH03), employ adjustable parameters to satisfy constraints measured in the local Universe. In recent years, however, theory and spatially resolved simulations of the turbulent, multiphase, star-forming interstellar medium (ISM) have begun to produce new first-principles models, which when fully developed can replace traditional subgrid prescriptions. This approach has advantages of being physically motivated and predictive rather than empirically tuned, and allowing for varying environmental conditions rather than being tied to local-Universe conditions. As a prototype of this new approach, by combining calibrations from the TIGRESS numerical framework with the pressure-regulated feedback-modulated (PRFM) theory, simple formulae can be obtained for both the gas depletion time and an effective equation of state. Considering galaxies in TNG50, we compare the “native” simulation outputs with postprocessed predictions from PRFM. At TNG50 resolution, the total midplane pressure is nearly equal to the total ISM weight, indicating that galaxies in TNG50 are close to satisfying vertical equilibrium. The measured gas scale height is also close to theoretical equilibrium predictions. The slopes of the effective equations of states are similar, but with effective velocity dispersion normalization from SH03 slightly larger than that from current TIGRESS simulations. Because of this and the decrease in PRFM feedback yield at high pressure, the PRFM model predicts shorter gas depletion times than the SH03 model at high densities and redshift. Our results represent a first step toward implementing new, numerically calibrated subgrid algorithms in cosmological galaxy formation simulations.

Marine heatwaves (MHWs) cause disruption to marine ecosystems, deleteriously impacting macroflora and fauna. However, effects on microorganisms are relatively unknown despite ocean temperature being a major determinant of assemblage structure. Using data from thousands of Southern Hemisphere samples, we reveal that during an “unprecedented” 2015/16 Tasman Sea MHW, temperatures approached or surpassed the upper thermal boundary of many endemic taxa. Temperate microbial assemblages underwent a profound transition to niche states aligned with sites over 1000 km equatorward, adapting to higher temperatures and lower nutrient conditions bought on by the MHW. MHW conditions also modulate seasonal patterns of microbial diversity and support novel assemblage compositions. The most significant affects of MHWs on microbial assemblages occurred during warmer months, when temperatures exceeded the upper climatological bounds. Trends in microbial response across several MHWs in different locations suggest these are emergent properties of temperate ocean warming, which may facilitate monitoring, prediction and adaptation efforts. Long-term monitoring revealed that a prolonged marine heatwave drove a profound transition in pelagic microbial assemblages, altering seasonal patterns of diversity and shifting niche conditions to those observed over 1000 km equatorward.

We report a ribosomal tag pyrosequencing study of the phylogenetic diversity of Archaea , Bacteria and Eucarya over a depth profile at the Hawaii Ocean Time-Series Station, ALOHA. The V9 region of the SSU rRNA gene was amplified from samples representing the epi- (10 m), meso- (800 m) and bathy- (4400 m) pelagia. The primers used are expected to amplify representatives of ∼80% of known phylogenetic diversity across all three domains. Comparisons of unique sequences revealed a remarkably low degree of overlap between communities at each depth. The 444 147 sequence tags analyzed represented 62 975 unique sequences. Of these, 3707 (5.9%) occurred at two depths, and only 298 (0.5%) were observed at all three depths. At this level of phylogenetic resolution, Bacteria diversity decreased with depth but was still equivalent to that reported elsewhere for different soil types. Archaea diversity was highest in the two deeper samples. Eucarya observations and richness estimates are almost one order of magnitude higher than any previous marine microbial Eucarya richness estimates. The associations of many Eucarya sequences with putative parasitic organisms may have significant impacts on our understanding of the mechanisms controlling host population density and diversity, and point to a more significant role for microbial Eucarya in carbon flux through the microbial loop. We posit that the majority of sequences detected from the deep sea that have closest matches to sequences from non-pelagic sources are indeed native to the marine environment, and are possibly responsible for key metabolic processes in global biogeochemical cycles.

Signaling pathways regulating proliferation, differentiation, and apoptosis are commonly mediated through protein-protein interactions as well as reversible phosphorylation of proteins. To facilitate the study of regulated protein-protein interactions in cells and living animals, we optimized firefly luciferase protein fragment complementation by secreening incremental truncation libraries of N- and C-terminal fragments of luciferase. Fused to the rapamycin-binding domain (FRB) of the kinase mammalian target of rapamycin and FK506-binding protein 12 (FKBP), respectively, the optimized FRB-N-terminal luciferase fragment (NLuc)/C-terminal luciferase fragment (CLuc)-FKBP luciferase complementation imaging (LCI) pair reconstituted luciferase activity in cells upon single-site binding of rapamycin in an FK506-competitive manner. LCI was used in three independent applications. In mice bearing implants of cells expressing the FRB-NLuc/CLuc-FKBP LCI pair, dose- and time-dependent luciferase activity allowed target-specific pharmacodynamic analysis of rapamycin-induced protein-protein interactions in vivo. In cells expressing a Cdc25C-NLuc/CLuc-14-3-3ε LCI pair, drug-mediated disruption of cell cycle regulated protein-protein interactions was demonstrated with the protein kinase inhibitor UCN-01 in a phosphoserine-dependent manner. When applied to IFN-γ-dependent activation of Janus kinase/signal transducer and activator of transcription 1 (STAT1), LCI revealed, in the absence of ligand-induced phosphorylation, STAT1 proteins existing in live cells as preformed dimers. Thus, optimized LCI provides a platform for near real-time detection and characterization of regulated and small molecule-induced protein-protein interactions in intact cells and living animals and should enable a wide range of novel applications in drug discovery, chemical genetics, and proteomics research.

Recirculating aquaculture systems (RAS) are agroecosystems for intensive on-land cultivation of products of fisheries. Practitioners that incorporate edible plant production into RAS refer to these facilities as aquaponic systems (AP). RAS have the potential to offset declining production levels of wild global fisheries while reducing waste and product distance to market, but system optimization is needed to reduce costs. Both RAS and AP rely on microbial consortia for maintaining water quality and promoting fish/plant health, but little is known about the microorganisms actually present. This lack of knowledge prevents optimization of designs and operational controls to target the growth of beneficial microbial species or consortia. The significance of our research is in identifying the common microorganisms that inhabit production RAS and AP and the operational factors that influence which microorganisms colonize and become abundant. Identifying these organisms is a first step toward advanced control of microbial activities that improve reproducibility and reduce costs. Flowthrough and pond aquaculture system microbiome management practices aim to mitigate fish disease and stress. However, the operational success of recirculating aquaculture systems (RAS) depends directly on system microbial community activities. In RAS, each component environment is engineered for a specific microbial niche for waste management, as the water continuously flowing through the system must be processed before returning to the rearing tank. In this study, we compared waste management component microbiomes (rearing tank water, pH correction tank, solid-waste clarifier, biofilter, and degassing tower) within a commercial-scale freshwater RAS by high-throughput 16S rRNA gene sequencing. To assess consistency among freshwater RAS microbiomes, we also compared the microbial community compositions of six aquaculture and aquaponic farms. Community assemblages reflected site and source water relationships, and the presence of a hydroponic subsystem was a major community determinant. In contrast to the facility-specific community composition, some sequence variants, mainly classified into Flavobacterium , Cetobacterium , the family Sphingomonadaceae , and nitrifying guilds of ammonia-oxidizing archaea and Nitrospira , were common across all facilities. The findings of this study suggest that, independently of system design, core taxa exist across RAS rearing similar fish species but that system design informs the individual aquatic microbiome assemblages. Future RAS design would benefit from understanding the roles of these core taxa and then capitalizing on their activities to further reduce system waste/added operational controls. IMPORTANCE Recirculating aquaculture systems (RAS) are agroecosystems for intensive on-land cultivation of products of fisheries. Practitioners that incorporate edible plant production into RAS refer to these facilities as aquaponic systems (AP). RAS have the potential to offset declining production levels of wild global fisheries while reducing waste and product distance to market, but system optimization is needed to reduce costs. Both RAS and AP rely on microbial consortia for maintaining water quality and promoting fish/plant health, but little is known about the microorganisms actually present. This lack of knowledge prevents optimization of designs and operational controls to target the growth of beneficial microbial species or consortia. The significance of our research is in identifying the common microorganisms that inhabit production RAS and AP and the operational factors that influence which microorganisms colonize and become abundant. Identifying these organisms is a first step toward advanced control of microbial activities that improve reproducibility and reduce costs.

Climate change-driven coral disease outbreaks have led to widespread declines in coral populations. Early work on coral genomics established that corals have a complex innate immune system, and whole-transcriptome gene expression studies have revealed mechanisms by which the coral immune system responds to stress and disease. The present investigation expands bioinformatic data available to study coral molecular physiology through the assembly and annotation of a reference transcriptome of the Caribbean reef-building coral, Orbicella faveolata . Samples were collected during a warm water thermal anomaly, coral bleaching event and Caribbean yellow band disease outbreak in 2010 in Puerto Rico. Multiplex sequencing of RNA on the Illumina GAIIx platform and de novo transcriptome assembly by Trinity produced 70,745,177 raw short-sequence reads and 32,463 O. faveolata transcripts, respectively. The reference transcriptome was annotated with gene ontologies, mapped to KEGG pathways, and a predicted proteome of 20,488 sequences was generated. Protein families and signaling pathways that are essential in the regulation of innate immunity across Phyla were investigated in-depth. Results were used to develop models of evolutionarily conserved Wnt, Notch, Rig-like receptor, Nod-like receptor, and Dicer signaling. O. faveolata is a coral species that has been studied widely under climate-driven stress and disease, and the present investigation provides new data on the genes that putatively regulate its immune system.

Heteromorphic flower development in Primula is controlled by the S locus. The S locus genes, which control anther position, pistil length and pollen size in pin and thrum flowers, have not yet been characterized. We have integrated S-linked genes, marker sequences and mutant phenotypes to create a map of the P. vulgaris S locus region that will facilitate the identification of key S locus genes. We have generated, sequenced and annotated BAC sequences spanning the S locus, and identified its chromosomal location. We have employed a combination of classical genetics and three-point crosses with molecular genetic analysis of recombinants to generate the map. We have characterized this region by Illumina sequencing and bioinformatic analysis, together with chromosome in situ hybridization. We present an integrated genetic and physical map across the P. vulgaris S locus flanked by phenotypic and DNA sequence markers. BAC contigs encompass a 1.5-Mb genomic region with 1Mb of sequence containing 82 S-linked genes anchored to overlapping BACs. The S locus is located close to the centromere of the largest metacentric chromosome pair. These data will facilitate the identification of the genes that orchestrate heterostyly in Primula and enable evolutionary analyses of the S locus.