Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE)

Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease characterized by esophageal eosinophilic infiltration. Thymic stromal lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and Th2-type adaptive immune responses in other allergic conditions, is overexpressed in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression in the esophageal epithelium are unknown. The objective of the current study was to characterize TSLP expression in human esophageal epithelium in EoE in vivo and to determine the role of food antigens upon epithelial TSLP expression in vitro. Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of active EoE (≥15 eos/hpf), inactive EoE (<15 eos/hpf) and non-EoE control subjects, and found that TSLP expression was restricted to the differentiated suprabasal layer of the epithelium in actively inflamed EoE biopsies. Consistent with these results in vivo, inducible TSLP protein secretion was higher in CaCl₂ differentiated telomerase-immortalized esophageal epithelial cells (EPC2-hTERT) compared to undifferentiated cells of the basal phenotype, following stimulation with the TLR3 ligand poly(I:C). To determine whether food antigens could directly induce epithelial TSLP secretion, differentiated and undifferentiated primary esophageal epithelial cells from EoE and non-EoE subjects were challenged with food antigens clinically relevant to EoE: Chicken egg ovalbumin (OVA), wheat, and milk proteins beta-lactoglobulin (blg) and beta-casein. Food antigens failed to induce TSLP secretion by undifferentiated cells; in contrast, only OVA induced TSLP secretion in differentiated epithelial cells from both EoE and control cell lines, an effect abolished by budesonide and NF-κb inhibition. Together, our study shows that specific food antigens can trigger innate immune mediated esophageal TSLP secretion, suggesting that esophageal epithelial cells at the barrier surface may play a significant role in the pathogenesis of EoE by regulating TSLP expression.     

Factors that Influence the Formation and Stability of Thin,Cryo-EM Specimens

Poor consistency of the ice thickness from one area of a cryo-electron microscope (cryo-EM) specimen grid to another, from one grid to the next, and from one type of specimen to another, motivates a reconsideration of how to best prepare suitably thin specimens. Here we first review the three related topics of wetting, thinning, and stability against dewetting of aqueous films spread over a hydrophilic substrate. We then suggest that the importance of there being a surfactant monolayer at the air-water interface of thin, cryo-EM specimens has been largely underappreciated. In fact, a surfactant layer (of uncontrolled composition and surface pressure) can hardly be avoided during standard cryo-EM specimen preparation. We thus suggest that better control over the composition and properties of the surfactant layer may result in more reliable production of cryo-EM specimens with the desired thickness.     

The Emergence of Synaesthesia in a Neuronal Network Model via Changes in Perceptual Sensitivity and Plasticity

Synaesthesia is an unusual perceptual experience in which an inducer stimulus triggers a percept in a different domain in addition to its own. To explore the conditions under which synaesthesia evolves, we studied a neuronal network model that represents two recurrently connected neural systems. The interactions in the network evolve according to learning rules that optimize sensory sensitivity. We demonstrate several scenarios, such as sensory deprivation or heightened plasticity, under which synaesthesia can evolve even though the inputs to the two systems are statistically independent and the initial cross-talk interactions are zero. Sensory deprivation is the known causal mechanism for acquired synaesthesia and increased plasticity is implicated in developmental synaesthesia. The model unifies different causes of synaesthesia within a single theoretical framework and repositions synaesthesia not as some quirk of aberrant connectivity, but rather as a functional brain state that can emerge as a consequence of optimising sensory information processing.     

Biocatalysis in seawater: Investigating a halotolerant ω‐transaminase capable of converting furfural in a seawater reaction medium

The increasing demand for freshwater and the continued depletion of available resources has led to a deepening global water crisis. Significant water consumption required by many biotechnological processes contributes to both the environmental and economic cost of this problem. Relatively few biocatalytic processes have been developed to utilize the more abundant supply of seawater, with seawater composition and salinity limiting its use with many mesophilic enzymes. We recently reported a salt tolerant ω‐transaminase enzyme, Ad2‐TAm, isolated from the genome of a halophilic bacterium, Halomonas sp. CSM‐2, from a Triassic period salt mine. In this study we aimed to demonstrate its applicability to biocatalytic reactions carried out in a seawater‐based medium. Ad2‐TAm was examined for its ability to aminate the industrially relevant substrate, furfural, in both seawater and freshwater‐based reaction systems. Furfural was aminated with 53.6% conversion in a buffered seawater system, displaying improved function versus freshwater. Ad2‐TAm outperformed the commonly employed commercial ω‐TAms from Chromobacterium violaceum and Vibrio fluvialis, both of which showed decreased conversion in seawater. Given the increasingly precarious availability of global freshwater, such applications of enzymes from halophiles have the ability to reduce demand for freshwater in large‐scale industrial processes, delivering considerable environmental and economic benefits.     

Structural Basis for CD96 Immune Receptor Recognition of Nectin-like Protein-5, CD155

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Impacts of natural history and exhibit factors on carnivore welfare

To improve the welfare of nonhuman animals under professional care, zoological institutions are continuously utilizing new methods to identify factors that lead to optimal welfare. Comparative methods have historically been used in the field of evolutionary biology but are increasingly being applied in the field of animal welfare. In the current study, data were obtained from direct behavioral observation and institutional records representing 80 individual animals from 34 different species of the order Carnivora. Data were examined to determine if a variety of natural history and animal management factors impacted the welfare of animals in zoological institutions. Output variables indicating welfare status included behavioral diversity, pacing, offspring production, and infant mortality. Results suggested that generalist species have higher behavioral diversity and offspring production in zoos compared with their specialist counterparts. In addition, increased minimum distance from the public decreased pacing and increased offspring production, while increased maximum distance from the public and large enclosure size decreased infant mortality. These results have implications for future exhibit design or renovation, as well as management practices and priorities for future research.     

Climate change does not affect the seafood quality of a commonly targeted fish

Climate change can affect marine and estuarine fish via alterations to their distributions, abundances, sizes, physiology and ecological interactions, threatening the provision of ecosystem goods and services. While we have an emerging understanding of such ecological impacts to fish, we know little about the potential influence of climate change on the provision of nutritional seafood to sustain human populations. In particular, the quantity, quality and/or taste of seafood may be altered by future environmental changes with implications for the economic viability of fisheries. In an orthogonal mesocosm experiment, we tested the influence of near‐future ocean warming and acidification on the growth, health and seafood quality of a recreationally and commercially important fish, yellowfin bream (Acanthopagrus australis). The growth of yellowfin bream significantly increased under near‐future temperature conditions (but not acidification), with little change in health (blood glucose and haematocrit) or tissue biochemistry and nutritional properties (fatty acids, lipids, macro‐ and micronutrients, moisture, ash and total N). Yellowfin bream appear to be highly resilient to predicted near‐future ocean climate change, which might be facilitated by their wide spatio‐temporal distribution across habitats and broad diet. Moreover, an increase in growth, but little change in tissue quality, suggests that near‐future ocean conditions will benefit fisheries and fishers that target yellowfin bream. The data reiterate the inherent resilience of yellowfin bream as an evolutionary consequence of their euryhaline status in often environmentally challenging habitats and imply their sustainable and viable fisheries into the future. We contend that widely distributed species that span large geographic areas and habitats can be “climate winners” by being resilient to the negative direct impacts of near‐future oceanic and estuarine climate change.