Crowleysteensen6033

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. 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. GGTI 298 mouse 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. The fecal Bifidobacterium in children correlated inversely with the consumption of complex carbohydrates and fruits after weaning. The specific cytokines related to the proliferation and maturation of immunity were found to increase after weaning. A decreasing level of primary bile acids and an increase of secondary bile acids were observed after weaning. This study highlights the change in the GI microbiota of infants to adult-type microbiota after weaning and identifies diet as a major contributing factor.Balint allows colleagues to explore emotions generated from doctor-patient interactions, complexities sometimes overlooked within traditional curricula. With an increasing burnout rate, evidence-based strategies to support trainee general practitioners (GPs) are needed and we investigated if Balint could be one way to improve this. There are no recent studies looking at Balint in UK GP training. Our aim was to establish GP trainees' understanding of the purpose of Balint and perceived advantages and disadvantages. Qualitative methodology was used to conduct semi-structured interviews with trainees and alumni participating in Balint within a suburban London Vocational Training Scheme. Emergent coding was performed and a phenomenological approach taken to thematic analysis. Eleven participants took part in the study. Balint provided a supportive, confidential outlet to help normalise trainees' feelings after challenging doctor-patient interactions. Multiple viewpoints, the chance to vent and a sense of comradery was unanimously enjoyed. Participants could see potential benefits for delivery of care, patient safety and remaining up-to-date. There was debate over inclusion of clinical management, and variation in preferred facilitation styles. Disparity in Balint contribution was attributed to differing personalities and confidence levels. With the growing demands of general practice, a flexible approach to Balint facilitation could add value in training by providing a peer platform to help address the hidden curriculum.Chronic stress which is common in the current society can be harmful to female reproduction and is associated with oocyte defects. However, the underlying mechanisms remain largely unknown. Herein, by using a mouse model of chronic restraint stress, we demonstrated that chronic stress could induce meiotic spindle abnormalities, chromatin misalignment, mitochondrial dysfunction and elevated ROS levels in oocytes in vivo, all of which were normalized by the administration of melatonin. Consistently, melatonin treatment during in vitro maturation also attenuated the meiotic defects induced by H2O2 by regulating autophagy and SIRT1, which could be abolished by SIRT1 inhibitor, Ex527 and autophagy inhibitor Bafilomycin A1 (Baf A1). These data indicate that melatonin can mitigate chronic stress-induced oxidative meiotic defects in mice MII oocytes by regulating SIRT1 and autophagy, providing new understanding for stress-related meiotic errors in MII oocytes and suggesting melatonin and SIRT1 could be new targets for optimizing culture system of oocytes as well as fertility management.Nuclear lamins form an elastic meshwork underlying the inner nuclear membrane and provide mechanical rigidity to the nucleus and maintain shape. Lamins also maintain chromosome positioning and play important roles in several nuclear processes like replication, DNA damage repair, transcription, and epigenetic modifications. LMNA mutations affect cardiac tissue, muscle tissues, adipose tissues to precipitate several diseases collectively termed as laminopathies. However, the rationale behind LMNA mutations and laminopathies continues to elude scientists. During interphase, several chromosomes form inter/intrachromosomal contacts inside nucleoplasm and several chromosomal loops also stretch out to make a 'loop-cluster' which are key players to regulate gene expressions. In this perspective, we have proposed that the lamin network in tandem with nuclear actin and myosin provide mechanical rigidity to the chromosomal contacts and facilitate loop-clusters movements. LMNA mutations thus might perturb the landscape of chromosomal contacts or loop-clusters positioning which can impair gene expression profile.Two strains of good fortune in my career were to stumble upon the Watson-Gilbert laboratory at Harvard when I entered graduate school in 1964, and to study gene regulation in bacteriophage λ when I was there. λ was almost entirely a genetic item a few years before, awaiting biochemical incarnation. Throughout my career I was a relentless consumer of the work of previous and current generations of λ geneticists. Empowered by this background, my laboratory made contributions in two areas. The first was regulation of early gene transcription in λ, the study of which began with the discovery of the Rho transcription termination factor, and the regulatory mechanism of transcription antitermination by the λ N protein, subjects of my thesis work. This was developed into a decades-long program during my career at Cornell, studying the mechanism of transcription termination and antitermination. The second area was the classic problem of prophage induction in response to cellular DNA damage, the study of which illuminated basic cellular processes to survive DNA damage. Expected final online publication date for the Annual Review of Microbiology, Volume 74 is September 8, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Influenza virus exploits cellular factors to complete each step of viral replication. Yet, multiple host proteins actively block replication. Consequently, infection success depends on the relative speed and efficacy at which both the virus and host use their respective effectors. Post-translational modifications (PTMs) afford both the virus and the host means to readily adapt protein function without the need for new protein production. Here we use influenza virus to address concepts common to all viruses, reviewing how PTMs facilitate and thwart each step of the replication cycle. We also discuss advancements in proteomic methods that better characterize PTMs. Although some effectors and PTMs have clear pro- or antiviral functions, PTMs generally play regulatory roles to tune protein functions, levels, and localization. Synthesis of our current understanding reveals complex regulatory schemes where the effects of PTMs are time and context dependent as the virus and host battle to control infection. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.For plant viruses, the ability to load into the vascular phloem and spread systemically within a host is an essential step in establishing a successful infection. However, access to the vascular phloem is highly regulated, representing a significant obstacle to virus loading, movement, and subsequent unloading into distal uninfected tissues. Recent studies indicate that during virus infection, phloem tissues are a source of significant transcriptional and translational alterations, with the number of virus-induced differentially expressed genes being four- to sixfold greater in phloem tissues than in surrounding nonphloem tissues. In addition, viruses target phloem-specific components as a means to promote their own systemic movement and disrupt host defense processes. Combined, these studies provide evidence that the vascular phloem plays a significant role in the mediation and control of host responses during infection and as such is a site of considerable modulation by the infecting virus. This review outlines the phloem responses and directed reprograming mechanisms that viruses employ to promote their movement through the vasculature.