Microbes must sense environmental stresses, transduce these signals and mount protective responses to survive in hostile environments. In this study we have tested the hypothesis that fungal stress ...signalling pathways have evolved rapidly in a niche-specific fashion that is independent of phylogeny. To test this hypothesis we have compared the conservation of stress signalling molecules in diverse fungal species with their stress resistance. These fungi, which include ascomycetes, basidiomycetes and microsporidia, occupy highly divergent niches from saline environments to plant or mammalian hosts.
The fungi displayed significant variation in their resistance to osmotic (NaCl and sorbitol), oxidative (H2O2 and menadione) and cell wall stresses (Calcofluor White and Congo Red). There was no strict correlation between fungal phylogeny and stress resistance. Rather, the human pathogens tended to be more resistant to all three types of stress, an exception being the sensitivity of Candida albicans to the cell wall stress, Calcofluor White. In contrast, the plant pathogens were relatively sensitive to oxidative stress. The degree of conservation of osmotic, oxidative and cell wall stress signalling pathways amongst the eighteen fungal species was examined. Putative orthologues of functionally defined signalling components in Saccharomyces cerevisiae were identified by performing reciprocal BLASTP searches, and the percent amino acid identities of these orthologues recorded. This revealed that in general, central components of the osmotic, oxidative and cell wall stress signalling pathways are relatively well conserved, whereas the sensors lying upstream and transcriptional regulators lying downstream of these modules have diverged significantly. There was no obvious correlation between the degree of conservation of stress signalling pathways and the resistance of a particular fungus to the corresponding stress.
Our data are consistent with the hypothesis that fungal stress signalling components have undergone rapid recent evolution to tune the stress responses in a niche-specific fashion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We simulate the formation of a realistic disk galaxy within the hierarchical scenario of structure formation and study its internal properties to the present epoch. We use a set of smoothed particle ...hydrodynamic (SPH) simulations, with a high dynamical range and force resolution, that include cooling, star formation, supernovae (SNe) feedback and a redshift-dependent UV background. We compare results from a lambda cold dark matter ( lambda CDM) simulation to a lambda warm dark matter ( lambda WDM) (2 keV) simulation that forms significantly less small-scale structure. We show how high mass and force resolution in both the gas and dark-matter components play an important role in solving the angular momentum catastrophe claimed from previous simulations of galaxy formation within the hierarchical framework. Hence, a large disk forms without the need of strong energy injection, the z = 0 galaxies lie close to the I band Tully-Fisher relation, and the stellar material in the disk component has a final specific angular momentum equal to 40% and 90% of the dark halo in the lambda CDM and lambda WDM models, respectively. If rescaled to the Milky Way, the lambda CDM galaxy has an overabundance of satellites, with a total mass in the stellar halo 40% of that in the bulge+disk system. The lambda WDM galaxy has a drastically reduced satellite population and a negligible stellar spheroidal component. Encounters with satellites play only a minor role in disturbing the disk. Satellites possess a variety of star formation histories linked to mergers and pericentric passages along their orbit around the primary galaxy. In both cosmologies, the galactic halo retains most of the baryons accreted and builds up a hot gas phase with a substantial X-ray emission. Therefore, while we have been successful in creating a realistic stellar disk in a massive galaxy within the lambda CDM scenario, energy injection emerges as necessary ingredient to reduce the baryon fraction in galactic halos, independent of the cosmology adopted.
In 2008, an increase in the prevalence of carbapenem-resistant Klebsiella pneumoniae was noted in a 286-bed tertiary case hospital in Colombia, where 84 patients (32 infected and 52 colonized) had ...positive cultures. The identified index patient came from Israel for a liver transplantation. High level carbapenem resistance was observed. Polymyxin B and tigecycline were the only two antibiotics that remained active. PCR-restriction fragment length polymorphism analysis and sequencing revealed blaKPC-3 in the major clone, which was indistinguishable from the K. pneumoniae carbapenemase-3-producing clone described previously in Israel. This exemplifies the threat posed by the global spread of K. pneumoniae carbapenemase-producing pathogens.
New developments in carbapenems Kattan, J.N.; Villegas, M.V.; Quinn, J.P.
Clinical microbiology and infection,
December 2008, Letnik:
14, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Antibiotic resistance among Gram-negative pathogens in hospitals is a growing threat to patients and is driving the increased use of carbapenems. Carbapenems are potent members of the β-lactam family ...of antibiotics, with a history of safety and efficacy for serious infections that exceeds 20 years. Original and review articles were identified from a Medline search (1979–2008). Reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and package inserts were also used. Carbapenems are effective in treating severe infections at diverse sites, with relatively low resistance rates and a favourable safety profile. Carbapenems are the β-lactams of choice for the treatment of infections caused by multidrug-resistant organisms. Optimized dosing of carbapenems should limit the emergence of resistance and prolong the utility of these agents. The newly approved doripenem should prove to be a valuable addition to the currently available carbapenems: imipenem, meropenem and ertapenem.
Linezolid is a new oxazolidinone antibiotic used to treat infections caused by vancomycin-resistant enterococci (VRE). In early clinical trials, emergence of resistance occurred rarely. We report ...clinical details and antibiotic susceptibility from five patients treated with linezolid for VRE infections who had resistant organisms isolated during therapy. Four were transplant patients receiving protracted courses of the drug; three cases were associated with treatment failure. One of 45 linezolid-treated patients developed resistance during therapy. Susceptibility testing should be done in all cases on starting therapy.
The major fungal pathogen of humans, Candida albicans, mounts robust responses to oxidative stress that are critical for its virulence. These responses counteract the reactive oxygen species (ROS) ...that are generated by host immune cells in an attempt to kill the invading fungus. Knowledge of the dynamical processes that instigate C. albicans oxidative stress responses is required for a proper understanding of fungus-host interactions. Therefore, we have adopted an interdisciplinary approach to explore the dynamical responses of C. albicans to hydrogen peroxide (H2O2). Our deterministic mathematical model integrates two major oxidative stress signalling pathways (Cap1 and Hog1 pathways) with the three major antioxidant systems (catalase, glutathione and thioredoxin systems) and the pentose phosphate pathway, which provides reducing equivalents required for oxidative stress adaptation. The model encapsulates existing knowledge of these systems with new genomic, proteomic, transcriptomic, molecular and cellular datasets. Our integrative approach predicts the existence of alternative states for the key regulators Cap1 and Hog1, thereby suggesting novel regulatory behaviours during oxidative stress. The model reproduces both existing and new experimental observations under a variety of scenarios. Time- and dose-dependent predictions of the oxidative stress responses for both wild type and mutant cells have highlighted the different temporal contributions of the various antioxidant systems during oxidative stress adaptation, indicating that catalase plays a critical role immediately following stress imposition. This is the first model to encapsulate the dynamics of the transcriptional response alongside the redox kinetics of the major antioxidant systems during H2O2 stress in C. albicans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Tobacco use disorder rates are elevated among people with serious mental illness.•Rates of tobacco use treatment in mental health settings are low.•Organizational interventions that improve training ...and emphasize a commitment to addressing TUD may improve treatment rates.
Tobacco use disorder (TUD) rates are 2–3 times higher among people with serious mental illness (SMI) than the general population. Clinicians working in outpatient community mental health clinics are well positioned to provide TUD treatment to this group, but rates of treatment provision are very low. Understanding factors associated with the provision of TUD treatment by mental health clinicians is a priority.
This study used baseline data from an ongoing cluster-randomized clinical trial evaluating two approaches to training clinicians to increase TUD treatment. Following a psychometric assessment of our assessment tool, the Smoking Knowledge, Attitudes, and Practices (S-KAP) instrument, a new factor structure was evaluated utilizing confirmatory factor analysis. Structural equation modeling was then used to examine the associations between TUD treatment practices and clinician, setting, and patient characteristics in a sample of 182 mental health clinicians across 10 mental health clinics.
Clinician but not setting or patient characteristics emerged as significant correlates of providing TUD treatment. Specifically, clinicians’ general ethical commitment to providing TUD services and perceptions of their skills in providing this type of care were associated with providing TUD treatment. In contrast, clinician perceptions of patient motivation, anticipated quit rates, or available setting resources were not significantly associated with providing TUD treatment.
Enhancing community mental health clinician TUD treatment skills and commitment to providing such services may reduce TUD rates among people with SMI. Future studies should evaluate interventions that target these factors.
Most extreme heat studies relate outdoor weather conditions to human morbidity and mortality. In developed nations, individuals spend ~90% of their time indoors. This pilot study investigated the ...indoor environments of people receiving emergency medical care in New York City, NY, U.S., from July to August 2013. The first objective was to determine the relative influence of outdoor conditions as well as patient characteristics and neighborhood sociodemographics on indoor temperature and specific humidity (N = 764). The second objective was to determine whether cardiovascular or respiratory cases experience hotter and more humid indoor conditions as compared to controls. Paramedics carried portable sensors into buildings where patients received care to passively monitor indoor temperature and humidity. The case–control study compared 338 respiratory cases, 291 cardiovascular cases, and 471 controls. Intuitively, warmer and sunnier outdoor conditions increased indoor temperatures. Older patients who received emergency care tended to occupy warmer buildings. Indoor‐specific humidity levels quickly adjusted to outdoor conditions. Indoor heat and humidity exposure above a 26 °C threshold increased (OR: 1.63, 95% CI: 0.98–2.68, P = 0.056), but not significantly, the proportion of respiratory cases. Indoor heat exposures were similar between cardiovascular cases and controls.
We report on multifrequency observations performed during 2012 December-2013 August of the first narrow-line Seyfert 1 galaxy detected in gamma rays, PMN J0948+0022 (z equal to 0.5846). A gamma-ray ...flare was observed by the Large Area Telescope on board Fermi during 2012 December-2013 January, reaching a daily peak flux in the 0.1-100 GeV energy range of (155 plus or minus 31)×10(exp −8) ph cm (exp −2) s (exp −1) on 2013 January 1, corresponding to an apparent isotropic luminosity of approximately 1.5×10)exp 48) erg s(exp −1). The gamma-ray flaring period triggered Swift and VERITAS observations in addition to radio and optical monitoring by OVRO, MOJAVE, and CRTS. A strong flare was observed in optical, UV, and X- rays on 2012 December 30, quasi-simultaneously to the gamma-ray flare, reaching a record flux for this source from optical to gamma rays. VERITAS observations at very high energy (E greater than 100 GeV) during 2013 January 6-17 resulted in an upper limit of F(sub greater than 0.2 TeV) less than 4.0 × 10(exp −12) ph cm(exp −2) s(exp −1). We compared the spectral energy distribution (SED) of the flaring state in 2013 January with that of an intermediate state observed in 2011. The two SEDs, modelled as synchrotron emission and an external Compton scattering of seed photons from a dust torus, can be modelled by changing both the electron distribution parameters and the magnetic field.
The synthesis of a range of novel 3-hydroxypyridin-4-ones and 3-hydroxypyran-4-ones linked with different coumarin substituents is described. These compounds have been developed in order to provide a ...series of molecular probes for the quantification of intracellular labile iron pools. An evaluation of the effect of iron(III) on fluorescence intensity was undertaken. Chelation of iron(III) causes quenching of fluorescence. The relationship between iron(III) concentration and the extent of fluorescence quenching indicates that the metal is chelated in a complex with a metal-to-ligand stoichiometry of 1:3. The fluorescence of hydroxypyridinone compounds was found to be more efficiently quenched by iron(III) than were the hydroxypyranones. The metal-to-ligand stoichiometry at which maximum quenching is observed was found to depend on the site at which coumarin is attached. The efficiency of fluorescence quenching by iron(III) is markedly influenced by solvent polarity and pH. The permeability of two representative fluorescent chelators across human erythrocyte ghost membranes was investigated. The rate of permeability for a series of probes was found to be related to the corresponding ClogP values.
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