Microbial utilization of renewable one-carbon compounds, such as methane, methanol, formic acid, and CO2, has emerged as a potential approach to increase the range of carbon sources for bioproduction ...and address climate change issues. Here, we modify the natural serine cycle present in methylotrophs and build an adapted pathway for Escherichia coli, which allows microorganism to condense methanol (or formate) together with bicarbonate to produce various products. We introduce the modified cycle into E. coli and demonstrate its capability for one-carbon assimilation through growth complementation and isotope labeling experiments. We also demonstrate conversion of methanol to ethanol by utilizing the modified serine cycle in an engineered E. coli strain, achieving a reaction yet to be accomplished by a one-pot chemical process. This work provides a platform to utilize various renewable one-carbon compounds as carbon sources for biosynthesis through a modified serine cycle in E. coli.
ABSTRACT
A method is presented to limit the volumetric density of repeating fast radio bursts (FRBs) based on the number (or lack) of repeating bursts identified in a survey. The method incorporates ...the instantaneous sensitivity of the instrument, its beam pattern, and the dwell time per pointing, as well as the energy and timing distribution of repeat bursts. Applied to the Australian Square Kilometre Array Pathfinder’s (ASKAP’s) Commensal Real-time ASKAP Fast Transients (CRAFT) ‘lat50’ survey, the presence of an FRB similar to FRB 121102 is excluded within a volume of 1.9 × 106 Mpc3 at 95 per cent confidence level (CL). Assuming a burst energy cut-off at 1042 erg, the 95 per cent CL upper limit on the population density of repeating FRBs in the current epoch is 27 Gpc−3, assuming isotropic (unbeamed) emission. This number is much lower than expected from even rare scenarios such as magnetar formation in gamma-ray bursts. Furthermore, the maximally allowed population underpredicts the observed number of single bursts in the survey. Comparisons with the observed dispersion measure distribution favours a larger population of less rapidly repeating objects, or the existence of a second population of non-repeating FRBs. In any scenario, FRB 121102 must be an atypical object.
A major goal of microbial community ecology is to understand the forces that structure community composition. Deterministic selection by specific environmental factors is sometimes important, but in ...other cases stochastic or ecologically neutral processes dominate. Lacking is a unified conceptual framework aiming to understand why deterministic processes dominate in some contexts but not others. Here we work toward such a framework. By testing predictions derived from general ecological theory we aim to uncover factors that govern the relative influences of deterministic and stochastic processes. We couple spatiotemporal data on subsurface microbial communities and environmental parameters with metrics and null models of within and between community phylogenetic composition. Testing for phylogenetic signal in organismal niches showed that more closely related taxa have more similar habitat associations. Community phylogenetic analyses further showed that ecologically similar taxa coexist to a greater degree than expected by chance. Environmental filtering thus deterministically governs subsurface microbial community composition. More importantly, the influence of deterministic environmental filtering relative to stochastic factors was maximized at both ends of an environmental variation gradient. A stronger role of stochastic factors was, however, supported through analyses of phylogenetic temporal turnover. Although phylogenetic turnover was on average faster than expected, most pairwise comparisons were not themselves significantly non-random. The relative influence of deterministic environmental filtering over community dynamics was elevated, however, in the most temporally and spatially variable environments. Our results point to general rules governing the relative influences of stochastic and deterministic processes across micro- and macro-organisms.
Fishes suspended in water are subject to the complex nature of three-dimensional flows. Often, these flows are the result of abiotic and biotic sources that alter otherwise uniform flows, which then ...have the potential to perturb the swimming motions of fishes. The goal of this review is to highlight key studies that have contributed to a mechanistic and behavioural understanding of how perturbing flows affect fish. Most of our understanding of fish behaviour in turbulence comes from observations of natural conditions in the field and laboratory studies employing controlled perturbations, such as vortices generated in the wake behind simple geometric objects. Laboratory studies have employed motion analysis, flow visualization, electromyography, respirometry and sensory deprecation techniques to evaluate the mechanisms and physiological costs of swimming in altered flows. Studies show that flows which display chaotic and wide fluctuations in velocity can repel fishes, while flows that have a component of predictability can attract fishes. The ability to maintain stability in three-dimensional flows, either actively with powered movements or passively using the posture and intrinsic compliance of the body and fins, plays a large role in whether fish seek out or avoid turbulence. Fish in schools or current-swept habitats can benefit from altered flows using two distinct though not mutually exclusive mechanisms: flow refuging (exploiting regions of reduced flow relative to the earth frame of reference) and vortex capture (harnessing the energy of environmental vortices). Integrating how the physical environment affects organismal biomechanics with the more complex issue of behavioural choice requires consideration beyond simple body motions or metabolic costs. A fundamental link between these two ways of thinking about animal behaviour is how organisms sense and process information from the environment, which determines when locomotor behaviour is initiated and modulated. New data are presented here which show that behaviour changes in altered flows when either the lateral line or vision is blocked, showing that fish rely on multi-modal sensory inputs to negotiate complex flow environments. Integrating biomechanics and sensory biology to understand how fish swim in turbulent flow at the organismal level is necessary to better address population-level questions in the fields of fisheries management and ecology.
Abstract Glaucoma is an ocular disorder characterized by the progressive loss of retinal ganglion cells (RGC) and their axons. There are various hypotheses concerning the cause of RGC death. ...Previously, glaucoma was defined by high intraocular pressure (IOP); during the past decade, however, glaucoma specialists have acknowledged that elevated IOP is the most important risk factor for glaucoma, but does not define the disease. Other factors such as genetics, blood flow, and excitotoxicity are suggested as potential causal factors for progressive RGC death observed in glaucoma. We review recent studies elucidating a possible role of low-grade inflammation as a causal factor in the pathogenesis of glaucoma.
Nanomaterials are popularly used in drug delivery, disease diagnosis and therapy. Among a number of functionalized nanomaterials such as carbon nanotubes, peptide nanostructures, liposomes and ...polymers, gold nanoparticles (Au NPs) make excellent drug and anticancer agent carriers in biomedical and cancer therapy application. Recent advances of synthetic technique improved the surface coating of Au NPs with accurate control of particle size, shape and surface chemistry. These make the gold nanomaterials a much easier and safer cancer agent and drug to be applied to the patient’s tumor. Although many studies on Au NPs have been published, more results are in the pipeline due to the rapid development of nanotechnology. The purpose of this review is to assess how the novel nanomaterials fabricated by Au NPs can impact biomedical applications such as drug delivery and cancer therapy. Moreover, this review explores the viability, property and cytotoxicity of various Au NPs.
Nanomaterials, such as nanoparticles, nanorods, nanosphere, nanoshells, and nanostars, are very commonly used in biomedical imaging and cancer therapy. They make excellent drug carriers, imaging ...contrast agents, photothermal agents, photoacoustic agents, and radiation dose enhancers, among other applications. Recent advances in nanotechnology have led to the use of nanomaterials in many areas of functional imaging, cancer therapy, and synergistic combinational platforms. This review will systematically explore various applications of nanomaterials in biomedical imaging and cancer therapy. The medical imaging modalities include magnetic resonance imaging, computed tomography, positron emission tomography, single photon emission computerized tomography, optical imaging, ultrasound, and photoacoustic imaging. Various cancer therapeutic methods will also be included, including photothermal therapy, photodynamic therapy, chemotherapy, and immunotherapy. This review also covers theranostics, which use the same agent in diagnosis and therapy. This includes recent advances in multimodality imaging, image-guided therapy, and combination therapy. We found that the continuous advances of synthesis and design of novel nanomaterials will enhance the future development of medical imaging and cancer therapy. However, more resources should be available to examine side effects and cell toxicity when using nanomaterials in humans.
A defining property of cytotoxic lymphocytes is their expression and regulated secretion of potent toxins, including the pore-forming protein perforin and serine protease granzymes. Until recently, ...mechanisms of pore formation and granzyme transfer into the target cell were poorly understood, but advances in structural and cellular biology have now begun to unravel how synergy between perforin and granzymes brings about target cell death. These and other advances are demonstrating the surprisingly broad pathophysiological roles of the perforin–granzyme pathway, and this has important implications for understanding immune homeostasis and for developing immunotherapies for cancer and other diseases. In particular, we are beginning to define and understand a range of human diseases that are associated with a failure to deliver active perforin to target cells. In this Review, we discuss the current understanding of the structural, cellular and clinical aspects of perforin and granzyme biology.
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