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  • Chappell Harris posted an update 12 hours, 32 minutes ago

    These results reinforce evidence for shared mechanisms that encode the quantity of both internally and externally generated events, and advance a useful general technique to test whether contextual effects like adaptation and serial dependence really affect sensory processing.Microbes occupy almost every niche within and on their human hosts. Whether colonizing the gut, mouth or bloodstream, microorganisms face temporal fluctuations in resources and stressors within their niche but we still know little of how environmental fluctuations mediate certain microbial phenotypes, notably antimicrobial-resistant ones. For instance, do rapid or slow fluctuations in nutrient and antimicrobial concentrations select for, or against, resistance? We tackle this question using an ecological approach by studying the dynamics of a synthetic and pathogenic microbial community containing two species, one sensitive and the other resistant to an antibiotic drug where the community is exposed to different rates of environmental fluctuation. We provide mathematical models, supported by experimental data, to demonstrate that simple community outcomes, such as competitive exclusion, can shift to coexistence and ecosystem bistability as fluctuation rates vary. Theory gives mechanistic insight into how these dynamical regimes are related. Importantly, our approach highlights a fundamental difference between resistance in single-species populations, the context in which it is usually assayed, and that in communities. While fast environmental changes are known to select against resistance in single-species populations, here we show that they can promote the resistant species in mixed-species communities. Our theoretical observations are verified empirically using a two-species Candida community.Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS (LmnaG609G/G609G) using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and a marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Importantly, the vascular function appears to arise normally from the low-stress environment of development, only to succumb progressively to pressure-related effects of the lamin A mutation and become extreme in the peri-morbid period. Because the dramatic life-threatening aortic phenotype manifests during the last third of life there may be a therapeutic window in maturity that could alleviate concerns with therapies administered during early periods of arterial development.Biochemical pathways and networks are central to cellular information processing. While a broad range of studies have dissected multiple aspects of information processing in biochemical pathways, the effect of spatial organization remains much less understood. It is clear that space is central to intracellular organization, plays important roles in cellular information processing and has been exploited in evolution; additionally, it is being increasingly exploited in synthetic biology through the development of artificial compartments, in a variety of ways. In this paper, we dissect different aspects of the interplay between spatial organization and biochemical pathways, by focusing on basic building blocks of these pathways covalent modification cycles and two-component systems, with enzymes which may be monofunctional or bifunctional. Our analysis of spatial organization is performed by examining a range of ‘spatial designs’ patterns of localization or non-localization of enzymes/substrates, theoretically a to engineering spatial organization of pathways in bottom-up synthetic biology in cellular and cell-free systems.Models of well-mixed chemical reaction networks (CRNs) have provided a solid foundation for the study of programmable molecular systems, but the importance of spatial organization in such systems has increasingly been recognized. In this paper, we explore an alternative chemical computing model introduced by Qian & Winfree in 2014, the surface CRN, which uses molecules attached to a surface such that each molecule only interacts with its immediate neighbours. Etrumadenant Expanding on the constructions in that work, we first demonstrate that surface CRNs can emulate asynchronous and synchronous deterministic cellular automata and implement continuously active Boolean logic circuits. We introduce three new techniques for enforcing synchronization within local regions, each with a different trade-off in spatial and chemical complexity. We also demonstrate that surface CRNs can manufacture complex spatial patterns from simple initial conditions and implement interesting swarm robotic behaviours using simple local rules. Throughout all example constructions of surface CRNs, we highlight the trade-off between the ability to precisely place molecules and the ability to precisely control molecular interactions. Finally, we provide a Python simulator for surface CRNs with an easy-to-use web interface, so that readers may follow along with our examples or create their own surface CRN designs.Gastrointestinal (GI) microbiota play an important role in human health and wellbeing and the first wave of gut microbes arrives mostly through vertical transmission from mother to child. This study has undertaken to understand the microbiota profile of healthy Southeast Asian mother-infant pairs. Here, we examined the fecal, vaginal and breast milk microbiota of Indonesian mothers and the fecal microbiota of their children from less than 1 month to 48 months old. To determine the immune status of children and the effect of diet at different ages, we examined the level of cytokines, bile acids in the fecal water and weaning food frequency. The fecal microbiota of the children before weaning contained mainly Bacteroides and Bifidobacterium, which presented at low abundance in the samples of mothers. After weaning, the fecal microbiome of children was mainly of the Prevotella type, with decreasing levels of Bifidobacterium, thus becoming more like the fecal microbiome of the mother. The abundance of infant fecal commensals generally correlated inversely with potential pathogens before weaning.

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