Pseudomonas genomes: diverse and adaptable Silby, Mark W; Winstanley, Craig; Godfrey, Scott A.C ...
FEMS microbiology reviews,
07/2011, Letnik:
35, Številka:
4
Journal Article
Recenzirano
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Abstract
Members of the genus Pseudomonas inhabit a wide variety of environments, which is reflected in their versatile metabolic capacity and broad potential for adaptation to fluctuating ...environmental conditions. Here, we examine and compare the genomes of a range of Pseudomonas spp. encompassing plant, insect and human pathogens, and environmental saprophytes. In addition to a large number of allelic differences of common genes that confer regulatory and metabolic flexibility, genome analysis suggests that many other factors contribute to the diversity and adaptability of Pseudomonas spp. Horizontal gene transfer has impacted the capability of pathogenic Pseudomonas spp. in terms of disease severity (Pseudomonas aeruginosa) and specificity (Pseudomonas syringae). Genome rearrangements likely contribute to adaptation, and a considerable complement of unique genes undoubtedly contributes to strain- and species-specific activities by as yet unknown mechanisms. Because of the lack of conserved phenotypic differences, the classification of the genus has long been contentious. DNA hybridization and genome-based analyses show close relationships among members of P. aeruginosa, but that isolates within the Pseudomonas fluorescens and P. syringae species are less closely related and may constitute different species. Collectively, genome sequences of Pseudomonas spp. have provided insights into pathogenesis and the genetic basis for diversity and adaptation.
Rising demand for food, fiber, and biofuels drives expanding irrigation withdrawals from surface water and groundwater. Irrigation efficiency and water savings have become watchwords in response to ...climate-induced hydrological variability, increasing freshwater demand for other uses including ecosystem water needs, and low economic productivity of irrigation compared to most other uses. We identify three classes of unintended consequences, presented here as paradoxes. Ever-tighter cycling of water has been shown to increase resource use, an example of the efficiency paradox. In the absence of effective policy to constrain irrigated-area expansion using "saved water", efficiency can aggravate scarcity, deteriorate resource quality, and impair river basin resilience through loss of flexibility and redundancy. Water scarcity and salinity effects in the lower reaches of basins (symptomatic of the scale paradox) may partly be offset over the short-term through groundwater pumping or increasing surface water storage capacity. However, declining ecological flows and increasing salinity have important implications for riparian and estuarine ecosystems and for non-irrigation human uses of water including urban supply and energy generation, examples of the sectoral paradox. This paper briefly considers three regional contexts with broadly similar climatic and water-resource conditions - central Chile, southwestern US, and south-central Spain - where irrigation efficiency directly influences basin resilience. The comparison leads to more generic insights on water policy in relation to irrigation efficiency and emerging or overdue needs for environmental protection.
Background. Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case ...definitions, standardized diagnostic approaches, and priorities for research. Methods. In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. Results. We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. Conclusions. We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.
Dimethyl fumarate (DMF) (BG-12, Tecfidera) is a fumaric acid ester (FAE) that was advanced as a multiple sclerosis (MS) therapy largely for potential neuroprotection as it was recognized that FAEs ...are capable of activating the antioxidative transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, DMF treatment in randomized controlled MS trials was associated with marked reductions in relapse rate and development of active brain MRI lesions, measures considered to reflect CNS inflammation. Here, we investigated the antiinflammatory contribution of Nrf2 in DMF treatment of the MS model, experimental autoimmune encephalomyelitis (EAE). C57BL/6 wild-type (WT) and Nrf2-deficient (Nrf2−/−) mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35–55 (p35–55) for EAE induction and treated with oral DMF or vehicle daily. DMF protected WT and Nrf2−/− mice equally well from development of clinical and histologic EAE. The beneficial effect of DMF treatment in Nrf2−/− and WT mice was accompanied by reduced frequencies of IFN-γ and IL-17–producing CD4⁺ cells and induction of antiinflammatory M2 (type II) monocytes. DMF also modulated B-cell MHC II expression and reduced the incidence of clinical disease in a B-cell–dependent model of spontaneous CNS autoimmunity. Our observations that oral DMF treatment promoted immune modulation and provided equal clinical benefit in acute EAE in Nrf2−/− and WT mice, suggest that the antiinflammatory activity of DMF in treatment of MS patients may occur through alternative pathways, independent of Nrf2.
Efficient TALEN-mediated gene knockout in livestock Carlson, Daniel F; Tan, Wenfang; Lillico, Simon G ...
Proceedings of the National Academy of Sciences - PNAS,
10/2012, Letnik:
109, Številka:
43
Journal Article
Recenzirano
Odprti dostop
Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs. Although zinc-finger nucleases enable a ...variety of genome modifications, their application to genetic engineering of livestock has been slowed by technical limitations of embryo-injection, culture of primary cells, and difficulty in producing reliable reagents with a limited budget. In contrast, we found that TALENs could easily be manufactured and that over half (23/36, 64%) demonstrate high activity in primary cells. Cytoplasmic injections of TALEN mRNAs into livestock zygotes were capable of inducing gene KO in up to 75% of embryos analyzed, a portion of which harbored biallelic modification. We also developed a simple transposon coselection strategy for TALEN-mediated gene modification in primary fibroblasts that enabled both enrichment for modified cells and efficient isolation of modified colonies. Coselection after treatment with a single TALEN-pair enabled isolation of colonies with mono- and biallelic modification in up to 54% and 17% of colonies, respectively. Coselection after treatment with two TALEN-pairs directed against the same chromosome enabled the isolation of colonies harboring large chromosomal deletions and inversions (10% and 4% of colonies, respectively). TALEN-modified Ossabaw swine fetal fibroblasts were effective nuclear donors for cloning, resulting in the creation of miniature swine containing mono- and biallelic mutations of the LDL receptor gene as models of familial hypercholesterolemia. TALENs thus appear to represent a highly facile platform for the modification of livestock genomes for both biomedical and agricultural applications.
We present deep, high-resolution (0 03, 200 pc) ALMA Band 7 observations covering the dust continuum and C ii λ157.7 m emission in four z ∼ 4.4-4.8 sub-millimeter galaxies (SMGs) selected from the ...ALESS and AS2UDS surveys. The data show that the rest-frame 160 m (observed 345 GHz) dust emission is consistent with smooth morphologies on kpc scales for three of the sources. One source, UDS 47.0, displays apparent substructure, but this is also consistent with a smooth morphology-as indicated by simulations showing that smooth exponential disks can appear clumpy when observed at the high angular resolution (0 03) and depth of these observations ( Jy beam−1). The four SMGs are bright C ii emitters. We extract C ii spectra from the high-resolution data, and recover ∼20%-100% of the C ii flux and ∼40%-80% of the dust continuum emission, compared to the previous lower-resolution observations. When tapered to 0 2 resolution, our maps recover ∼80%-100% of the continuum emission, indicating that ∼60% of the emission is resolved out on ∼200 pc scales. We find that the C ii emission in high-redshift galaxies is more spatially extended than the rest-frame 160 m dust continuum by a factor of 1.6 0.4. By considering the / ratio as a function of the star formation rate surface density ( ), we revisit the C ii deficit and suggest that the decline in the / ratio as a function of is consistent with local processes. We also explore the physical drivers that may be responsible for these trends and can give rise to the properties found in the densest regions of SMGs.
T cells from neuromyelitis optica (NMO) patients, which recognize the immunodominant epitope of aquaporin‐4, exhibit Th17 polarization and cross‐react with a homologous sequence of a Clostridium ...perfringens adenosine triphosphate‐binding cassette transporter. Therefore, this commensal microbe might participate in NMO pathogenesis. We examined the gut microbiome by PhyloChip G3 from 16 NMO patients, 16 healthy controls (HC), and 16 multiple sclerosis patients. A significant difference in the abundance of several microbial communities was observed between NMO and HC (Adonis test, p = 0.001). Strikingly, C. perfringens was overrepresented in NMO (p = 5.24 × 10−8). These observations support a potential role for C. perfringens in NMO pathogenesis. Ann Neurol 2016;80:443–447
Objective:
Aquaporin 4 (AQP4)‐specific autoantibodies in neuromyelitis optica (NMO) are immunoglobulin (Ig)G1, a T cell‐dependent Ig subclass, indicating that AQP4‐specific T cells participate in NMO ...pathogenesis. Our goal was to identify and characterize AQP4‐specific T cells in NMO patients and healthy controls (HC).
Methods:
Peripheral blood T cells from NMO patients and HC were examined for recognition of AQP4 and production of proinflammatory cytokines. Monocytes were evaluated for production of T cell‐polarizing cytokines and expression of costimulatory molecules.
Results:
T cells from NMO patients and HC proliferated to intact AQP4 or AQP4 peptides (p11–30, p21–40, p61–80, p131–150, p156–170, p211–230, and p261–280). T cells from NMO patients demonstrated greater proliferation to AQP4 than those from HC, and responded most vigorously to p61–80, a naturally processed immunodominant determinant of intact AQP4. T cells were CD4+, and corresponding to association of NMO with human leukocyte antigen (HLA)‐DRB1*0301 and DRB3, AQP4 p61–80‐specific T cells were HLA‐DR restricted. The T‐cell epitope within AQP4 p61–80 was mapped to 63–76, which contains 10 residues with 90% homology to a sequence within Clostridium perfringens adenosine triphosphate‐binding cassette (ABC) transporter permease. T cells from NMO patients proliferated to this homologous bacterial sequence, and cross‐reactivity between it and self‐AQP4 was observed, supporting molecular mimicry. In NMO, AQP4 p61–80‐specific T cells exhibited Th17 polarization, and furthermore, monocytes produced more interleukin 6, a Th17‐polarizing cytokine, and expressed elevated CD40 and CD80 costimulatory molecules, suggesting innate immunologic dysfunction.
Interpretation:
AQP4‐specific T‐cell responses are amplified in NMO, exhibit a Th17 bias, and display cross‐reactivity to a protein of an indigenous intestinal bacterium, providing new perspectives for investigating NMO pathogenesis. ANN NEUROL 2012;
The Fukushima Daiichi nuclear power plant (FDNPP) incident released a significant mass of radioactive material into the atmosphere. An estimated 22% of this material fell out over land following the ...incident. Immediately following the disaster, there was a severe lack of information not only pertaining to the identity of the radioactive material released, but also its distribution as fallout in the surrounding regions. Indeed, emergency aid groups including the UN did not have sufficient location specific radiation data to accurately assign exclusion and evacuation zones surrounding the plant in the days and weeks following the incident. A newly developed instrument to provide rapid and high spatial resolution assessment of radionuclide contamination in the environment is presented. The device consists of a low cost, lightweight, unmanned aerial platform with a microcontroller and integrated gamma spectrometer, GPS and LIDAR. We demonstrate that with this instrument it is possible to rapidly and remotely detect ground-based radiation anomalies with a high spatial resolution (<1 m). Critically, as the device is remotely operated, the user is removed from any unnecessary or unforeseen exposure to elevated levels of radiation.
•We present a new instrument for the remote detection of radiation in the environment.•The integration of sensors payload and UAV vehicle is shown.•The device is demonstrated to detect a single radiation anomalies remotely.•The device is demonstrated to map two radiation anomalies remotely and with a high spatial resolution.
Summary
The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane‐bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in ...human biology because they are generated by combinatorial rearrangement of the genomic DNA. The diversity of receptors so generated in populations of lymphocytes enables the human immune system to recognize antigens expressed by pathogens, but also underlies the pathological specificity of autoimmune diseases and the mistargeted immunity in allergies. Several recent technological developments, foremost among them the invention of high‐throughput DNA sequencing instruments, have enabled much deeper and thorough evaluation of clones of human B cells and T cells and the antigen receptors they express during physiological and pathogenic immune responses. The evolutionary struggles between host adaptive immune responses and populations of pathogens are now open to greater scrutiny, elucidation of the underlying reasons for successful or failed immunity, and potential predictive modeling, than ever before. Here we give an overview of the foundations, recent progress, and future prospects in this dynamic area of research.
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![The Dust and [C ii] Morphol...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0004-637X/small "The Dust and [C ii] Morphologies of Redshift ∼4.5 Sub-millimeter Galaxies at ∼200 pc Resolution: The Absence of Large Clumps in the Interstellar Medium at High-redshift")
