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101.
Emerging infectious diseases represent a major challenge to human health worldwide. The risk of evolving new infectious pathogens has been intensifying due to urbanization, demographic changes, air travel, inappropriate use of antibiotics, and climate change. These pathogens can affect humans from urban centers to the remotest corners of the globe. Far from being a scourge of the past, infectious diseases are relevant for the world today. 相似文献
102.
Babu M Beloglazova N Flick R Graham C Skarina T Nocek B Gagarinova A Pogoutse O Brown G Binkowski A Phanse S Joachimiak A Koonin EV Savchenko A Emili A Greenblatt J Edwards AM Yakunin AF 《Molecular microbiology》2011,79(2):484-502
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR-associated protein that is common to all CRISPR-containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single-stranded and branched DNAs including Holliday junctions, replication forks and 5'-flaps. The crystal structure of YgbT and site-directed mutagenesis have revealed the potential active site. Genome-wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR-Cas system have a function in DNA repair. 相似文献
103.
Taylor Richards Kavindiya Modarage Charlotte Dean Aidan McCarthy-Boxer Helen Hilton Chris Esapa Jill Norman Patricia Wilson Paraskevi Goggolidou 《生物化学与生物物理学报:疾病的分子基础》2019,1865(2):378-390
Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a genetic disorder with an incidence of ~1:20,000 that manifests in a wide range of renal and liver disease severity in human patients and can lead to perinatal mortality. ARPKD is caused by mutations in PKHD1, which encodes the large membrane protein, Fibrocystin, required for normal branching morphogenesis of the ureteric bud during embryonic renal development. The variation in ARPKD phenotype suggests that in addition to PKHD1 mutations, other genes may play a role, acting as modifiers of disease severity. One such pathway involves non-canonical Wnt/Planar Cell Polarity (PCP) signalling that has been associated with other cystic kidney diseases, but has not been investigated in ARPKD. Analysis of the AtminGpg6 mouse showed kidney, liver and lung abnormalities, suggesting it as a novel mouse tool for the study of ARPKD. Further, modulation of Atmin affected Pkhd1 mRNA levels, altered non-canonical Wnt/PCP signalling and impacted cellular proliferation and adhesion, although Atmin does not bind directly to the C-terminus of Fibrocystin. Differences in ATMIN and VANGL2 expression were observed between normal human paediatric kidneys and age-matched ARPKD kidneys. Significant increases in ATMIN, WNT5A, VANGL2 and SCRIBBLE were seen in human ARPKD versus normal kidneys; no substantial differences were seen in DAAM2 or NPHP2. A striking increase in E-cadherin was also detected in ARPKD kidneys. This work indicates a novel role for non-canonical Wnt/PCP signalling in ARPKD and suggests ATMIN as a modulator of PKHD1. 相似文献
104.
Chris T. Jones Susanne E. Craig Audrey B. Barnett Hugh L. MacIntyre John J. Cullen 《Journal of phycology》2014,50(2):341-355
An equation for the rate of photosynthesis as a function of irradiance introduced by T. T. Bannister included an empirical parameter b to account for observed variations in curvature between the initial slope and the maximum rate of photosynthesis. Yet researchers have generally favored equations with fixed curvature, possibly because b was viewed as having no physiological meaning. We developed an analytic photosynthesis‐irradiance equation relating variations in curvature to changes in the degree of connectivity between photosystems, and also considered a recently published alternative, based on changes in the size of the plastoquinone pool. When fitted to a set of 185 observed photosynthesis‐irradiance curves, it was found that the Bannister equation provided the best fit more frequently compared to either of the analytic equations. While Bannister's curvature parameter engendered negligible improvement in the statistical fit to the study data, we argued that the parameter is nevertheless quite useful because it allows for consistent estimates of initial slope and saturation irradiance for observations exhibiting a range of curvatures, which would otherwise have to be fitted to different fixed‐curvature equations. Using theoretical models, we also found that intra‐ and intercellular self‐shading can result in biased estimates of both curvature and the saturation irradiance parameter. We concluded that Bannister's is the best currently available equation accounting for variations in curvature precisely because it does not assign inappropriate physiological meaning to its curvature parameter, and we proposed that b should be thought of as the expression of the integration of all factors impacting curvature. 相似文献
105.
Kathy Darragh Gabriela Montejo‐Kovacevich Krzysztof M. Kozak Colin R. Morrison Clarisse M. E. Figueiredo Jonathan S. Ready Camilo Salazar Mauricio Linares Kelsey J. R. P. Byers Richard M. Merrill W. Owen McMillan Stefan Schulz Chris D. Jiggins 《Ecology and evolution》2020,10(9):3895-3918
In many animals, mate choice is important for the maintenance of reproductive isolation between species. Traits important for mate choice and behavioral isolation are predicted to be under strong stabilizing selection within species; however, such traits can also exhibit variation at the population level driven by neutral and adaptive evolutionary processes. Here, we describe patterns of divergence among androconial and genital chemical profiles at inter‐ and intraspecific levels in mimetic Heliconius butterflies. Most variation in chemical bouquets was found between species, but there were also quantitative differences at the population level. We found a strong correlation between interspecific chemical and genetic divergence, but this correlation varied in intraspecific comparisons. We identified “indicator” compounds characteristic of particular species that included compounds already known to elicit a behavioral response, suggesting an approach for identification of candidate compounds for future behavioral studies in novel systems. Overall, the strong signal of species identity suggests a role for these compounds in species recognition, but with additional potentially neutral variation at the population level. 相似文献
106.
Cultured gill epithelia as models for the freshwater fish gill 总被引:1,自引:0,他引:1
Wood CM Kelly SP Zhou B Fletcher M O'Donnell M Eletti B Pärt P 《Biochimica et biophysica acta》2002,1566(1-2):72-83
We review recent progress in the development of models for the freshwater teleost gill based on reconstructed flat epithelia grown on permeable filter supports in primary culture. Methods are available for single-seeded insert (SSI) preparations consisting of pavement cells (PVCs) only from trout and tilapia, and double-seeded insert (DSI) preparations from trout, containing both PVCs (85%) and mitochondria-rich cells (MRCs, 15%), as in the intact gill. While there are some quantitative differences, both SSI and DSI epithelia manifest electrical and passive permeability characteristics typical of intact gills and representative of very tight epithelia. Both preparations withstand apical freshwater exposure, exhibiting large increases in transepithelial resistance (TER), negative transepithelial potential (TEP), and low rates of ion loss, but there is only a small active apical-to-basolateral "influx" of Cl(-) (and not of Na(+)). Responses to various hormonal treatments are described (thyroid hormone T3, prolactin, and cortisol). Cortisol has the most marked effects, stimulating Na(+),K(+)-ATPase activity and promoting active Na(+) and Cl(-) influxes in DSI preparations, and raising TER and reducing passive ion effluxes in both epithelia via reductions in paracellular permeability. Experiments using DSI epithelia lacking Na(+) uptake demonstrate that both NH(3) and NH(4)(+) diffusion occur, but are not large enough to account for normal rates of branchial ammonia excretion, suggesting that Na(+)-linked carrier-mediated processes are important for ammonia excretion in vivo. Future research goals are suggested. 相似文献
107.
Johnsen K Maier C Sanchez F Anderson P Butnor J Waring R Linder S 《Plant, cell & environment》2007,30(1):128-134
Quantifying below-ground carbon (C) allocation is particularly difficult as methods usually disturb the root-mycorrhizal-soil continuum. We reduced C allocation below ground of loblolly pine trees by: (1) physically girdling trees and (2) physiologically girdling pine trees by chilling the phloem. Chilling reduced cambium temperatures by approximately 18 degrees C. Both methods rapidly reduced soil CO2 efflux, and after approximately 10 days decreased net photosynthesis (P(n)), the latter indicating feedback inhibition. Chilling decreased soil-soluble C, indicating that decreased soil CO2 efflux may have been mediated by a decrease in root C exudation that was rapidly respired by microbes. These effects were only observed in late summer/early autumn when above-ground growth was minimal, and not in the spring when above-ground growth was rapid. All of the effects were rapidly reversed when chilling was ceased. In fertilized plots, both chilling and physical girdling methods reduced soil CO2 efflux by approximately 8%. Physical girdling reduced soil CO2 efflux by 26% in non-fertilized plots. This work demonstrates that phloem chilling provides a non-destructive alternative to reducing the movement of recent photosynthate below the point of chilling to estimate C allocation below ground on large trees. 相似文献
108.
Trees tolerate an extreme heatwave via sustained transpirational cooling and increased leaf thermal tolerance 下载免费PDF全文
John E. Drake Mark G. Tjoelker Angelica Vårhammar Belinda E. Medlyn Peter B. Reich Andrea Leigh Sebastian Pfautsch Chris J. Blackman Rosana López Michael J. Aspinwall Kristine Y. Crous Remko A. Duursma Dushan Kumarathunge Martin G. De Kauwe Mingkai Jiang Adrienne B. Nicotra David T. Tissue Brendan Choat Owen K. Atkin Craig V. M. Barton 《Global Change Biology》2018,24(6):2390-2402
Heatwaves are likely to increase in frequency and intensity with climate change, which may impair tree function and forest C uptake. However, we have little information regarding the impact of extreme heatwaves on the physiological performance of large trees in the field. Here, we grew Eucalyptus parramattensis trees for 1 year with experimental warming (+3°C) in a field setting, until they were greater than 6 m tall. We withheld irrigation for 1 month to dry the surface soils and then implemented an extreme heatwave treatment of 4 consecutive days with air temperatures exceeding 43°C, while monitoring whole‐canopy exchange of CO2 and H2O, leaf temperatures, leaf thermal tolerance, and leaf and branch hydraulic status. The heatwave reduced midday canopy photosynthesis to near zero but transpiration persisted, maintaining canopy cooling. A standard photosynthetic model was unable to capture the observed decoupling between photosynthesis and transpiration at high temperatures, suggesting that climate models may underestimate a moderating feedback of vegetation on heatwave intensity. The heatwave also triggered a rapid increase in leaf thermal tolerance, such that leaf temperatures observed during the heatwave were maintained within the thermal limits of leaf function. All responses were equivalent for trees with a prior history of ambient and warmed (+3°C) temperatures, indicating that climate warming conferred no added tolerance of heatwaves expected in the future. This coordinated physiological response utilizing latent cooling and adjustment of thermal thresholds has implications for tree tolerance of future climate extremes as well as model predictions of future heatwave intensity at landscape and global scales. 相似文献
109.
Chris Molenaar Jan-Maarten Teuben Robert J. Heetebrij Hans J. Tanke Jan Reedijk 《Journal of biological inorganic chemistry》2000,5(5):655-665
The cellular distribution and processing pathways of two platinum compounds, modeling the antitumor drug cisplatin (cDDP) in human osteosarcoma (U2-OS) cells is reported. A [Pt(en)Cl] entity has been covalently linked to a carboxyfluorescein diacetate (CFDA) moiety and to a dinitrophenyl (DNP) moiety. The two different constructs were administered to living cell cultures that were analyzed using digital fluorescence microscopy. The non-fluorescent CFDA construct becomes fluorescent after cellular uptake and subsequent acetate hydrolysis by esterases, and is therefore suitable to monitor platinum in living cells; the DNP construct can be visualized by immunocytochemistry and consequently serves as a control. Both complexes were readily internalized by the cells, and localized throughout the whole cell. After 2-3 h the complex accumulated in the nucleus, but 6-8 h after incubation a punctuate staining of a cytoplasmic region was observed, that persisted and became more pronounced after 24 h. The overall fluorescence in the cell decreased over time, implying a secretion of the platinum complex. Surprisingly, the accumulation remained visible after 72 h. Co-localization experiments with a Golgi apparatus-selective stain indicate the involvement of Golgi vesicles in intracellular processing of cisplatin-derived complexes. Immunocytochemical studies, using the DNP derivative, resulted in very similar images as obtained with the CFDA construct. CFDA-boc (a non-platinum-containing fluorescein derivative) was used as control: a faint staining throughout the whole cell was observed. Cisplatin-resistant U2-OS/Pt cells showed staining patterns very similar to the U2-OS cells using both platinum constructs. This study illustrates that only a very small portion of the platinum complex eventually remains bound to DNA, as after 24 h no significant fluorescence could be observed in the nucleus. Cisplatin-derived complexes with fluorescent tags afford a new insight into the cellular processing of these complexes and therefore may contribute to further unraveling of the mechanism of platinum antitumor complexes. 相似文献
110.