is an important opportunistic pathogen that commonly causes nosocomial infections and contributes to substantial morbidity and mortality. We sought to investigate the antibiotic resistance profile, ...pathogenic potential and the clonal relationships between
(
= 25) isolated from patients and sources at a tertiary care hospital's intensive care units (ICUs) in the northern region of Brazil. Most of
isolates (
= 21, 84%) were classified as multidrug resistant (MDR) with high-level resistance to β-lactams, aminoglycosides, quinolones, tigecycline, and colistin. All the 25 isolates presented extended-spectrum beta-lactamase-producing (ESBL), including carbapenemase producers, and carried the
(100%),
(100%),
variants (
= 24, 96%),
group (
= 21, 84%) and
group (
= 18, 72%) genes. The K2 serotype was found in 4% (
= 1) of the isolates, and the K1 was not detected. The virulence-associated genes found among the 25 isolates were
D (
= 24, 96%),
H-1 (
= 22, 88%),
B (100%),
A (
= 10, 40%),
S (
= 15, 60%). The genes related with efflux pumps and outer membrane porins found were
(100%),
C (
= 24, 96%),
K (
= 22, 88%),
K35 (
= 15, 60%), and
K36 (
= 7, 28%). ERIC-PCR was employed to determine the clonal relationship between the different isolated strains. The obtained ERIC-PCR patterns revealed that the similarity between isolates was above 70%. To determine the sequence types (STs) a multilocus sequence typing (MLST) assay was used. The results indicated the presence of high-risk international clones among the isolates. In our study, the wide variety of MDR
harboring β-lactams and virulence genes strongly suggest a necessity for the implementation of effective strategies to prevent and control the spread of antibiotic resistant infections.
It has been 20 years since West Nile virus first emerged in the Americas, and since then, little progress has been made to control outbreaks caused by this virus. After its first detection in New ...York in 1999, West Nile virus quickly spread across the continent, causing an epidemic of human disease and massive bird die-offs. Now the virus has become endemic to the United States, where an estimated 7 million human infections have occurred, making it the leading mosquito-borne virus infection and the most common cause of viral encephalitis in the country. To bring new attention to one of the most important mosquito-borne viruses in the Americas, we provide an interactive review using Nextstrain: a visualization tool for real-time tracking of pathogen evolution (nextstrain.org/WNV/NA). Nextstrain utilizes a growing database of more than 2,000 West Nile virus genomes and harnesses the power of phylogenetics for students, educators, public health workers, and researchers to visualize key aspects of virus spread and evolution. Using Nextstrain, we use virus genomics to investigate the emergence of West Nile virus in the U S, followed by its rapid spread, evolution in a new environment, establishment of endemic transmission, and subsequent international spread. For each figure, we include a link to Nextstrain to allow the readers to directly interact with and explore the underlying data in new ways. We also provide a brief online narrative that parallels this review to further explain the data and highlight key epidemiological and evolutionary features (nextstrain.org/narratives/twenty-years-of-WNV). Mirroring the dynamic nature of outbreaks, the Nextstrain links provided within this paper are constantly updated as new West Nile virus genomes are shared publicly, helping to stay current with the research. Overall, our review showcases how genomics can track West Nile virus spread and evolution, as well as potentially uncover novel targeted control measures to help alleviate its public health burden.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The emerging view of Nε-lysine acetylation in eukaryotes is of a relatively abundant post-translational modification (PTM) that has a major impact on the function, structure, stability and/or ...location of thousands of proteins involved in diverse cellular processes. This PTM is typically considered to arise by the donation of the acetyl group from acetyl-coenzyme A (acCoA) to the ε-amino group of a lysine residue that is reversibly catalyzed by lysine acetyltransferases and deacetylases. Here, we provide genetic, mass spectrometric, biochemical and structural evidence that Nε-lysine acetylation is an equally abundant and important PTM in bacteria. Applying a recently developed, label-free and global mass spectrometric approach to an isogenic set of mutants, we detected acetylation of thousands of lysine residues on hundreds of Escherichia coli proteins that participate in diverse and often essential cellular processes, including translation, transcription and central metabolism. Many of these acetylations were regulated in an acetyl phosphate (acP)-dependent manner, providing compelling evidence for a recently reported mechanism of bacterial Nε-lysine acetylation. These mass spectrometric data, coupled with observations made by crystallography, biochemistry, and additional mass spectrometry showed that this acP-dependent acetylation is both non-enzymatic and specific, with specificity determined by the accessibility, reactivity and three-dimensional microenvironment of the target lysine. Crystallographic evidence shows acP can bind to proteins in active sites and cofactor binding sites, but also potentially anywhere molecules with a phosphate moiety could bind. Finally, we provide evidence that acP-dependent acetylation can impact the function of critical enzymes, including glyceraldehyde-3-phosphate dehydrogenase, triosephosphate isomerase, and RNA polymerase.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The incidence of breast cancer increased in the United States until circa 2000 then decreased, mostly among women with estrogen receptor (ER)-positive cancers. Time trends provide ...important clues for cancer etiology and prevention; however, the observed trends of ER-positive and ER-negative breast cancers can be biased by missing ER data.
Methods
We developed a simple imputation method to correct invasive female breast cancer incidence for missing or unknown ER expression, using nationally representative data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program during 1980-2008, including 588 720 invasive female breast cancer patients with 471 336 233 woman-years of follow-up. Corrected rates of ER-positive and ER-negative breast cancers were used to calculate age-standardized incidence rates, estimated annual percentage changes, and projections derived from age-period-cohort models.
Results
The recent decrease in the incidence of breast cancer overall stabilized near 200 per 100 000 woman-years by 2007-2008, reflecting a transient decrease in ER-positive cancers and a steady decrease in ER-negative cancers. The projected incidence rate for breast cancer overall through the year 2016 was similar to the incidence rate during 2007-2008. In contrast, rates of ER-positive breast cancers were projected to increase 5.3% (95% confidence interval = 5.2% to 5.4%), whereas rates of ER-negative breast cancers were projected to decrease 11.4% (95% confidence interval = 11.3% to 11.6%) during 2009-2016.
Conclusion
Recent changes in breast cancer incidence overall reflect the superimposition of divergent trends in ER-positive and ER-negative cancers. If current trends continue, the incidence of ER-positive breast cancers will increase, the incidence of ER-negative breast cancers will continue to decrease, and the incidence of breast cancer overall will remain similar to its current level.
Breast cancer is a heterogeneous disease, divisible into a variable number of clinical subtypes. A fundamental question is how many etiological classes underlie the clinical spectrum of breast ...cancer? An etiological subtype reflects a grouping with a common set of causes, whereas a clinical subtype represents a grouping with similar prognosis and/or prediction. Herein, we review the evidence for breast cancer etiological heterogeneity. We then evaluate the etiological evidence with mRNA profiling data. A bimodal age distribution at diagnosis with peak frequencies near ages 50 and 70 years is a fundamental characteristic of breast cancer for important tumor features, clinical characteristics, risk factor profiles, and molecular subtypes. The bimodal peak frequencies at diagnosis divide breast cancer overall into a "mixture" of two main components in varying proportions in different cancer populations. The first breast cancer tends to arise early in life with modal age-at-diagnosis near 50 years and generally behaves aggressively. The second breast cancer occurs later in life with modal age near 70 years and usually portends a more indolent clinical course. These epidemiological and molecular data are consistent with a two-component mixture model and compatible with a hierarchal view of breast cancers arising from two main cell types of origin. Notwithstanding the potential added value of more detailed categorizations for personalized breast cancer treatment, we suggest that the development of better criteria to identify the two proposed etiologic classes would advance breast cancer research and prevention.
Active galactic nuclei (AGNs) that show strong rest-frame optical/UV variability in their blue continuum and broad line emission are classified as changing-look AGN, or at higher luminosities, ...changing-look quasars (CLQs). These surprisingly large and sometimes rapid transitions challenge accepted models of quasar physics and duty cycles, offer several new avenues for study of quasar host galaxies, and open a wider interpretation of the cause of differences between broad and narrow-line AGN. To better characterize extreme quasar variability, we present follow-up spectroscopy as part of a comprehensive search for CLQs across the full Sloan Digital Sky Survey (SDSS) footprint using spectroscopically confirmed quasars from the SDSS DR7 catalog. Our primary selection requires large-amplitude ( mag, mag) variability over any of the available time baselines probed by the SDSS and Pan-STARRS 1 surveys. We employ photometry from the Catalina Sky Survey to verify variability behavior in CLQ candidates where available, and confirm CLQs using optical spectroscopy from the William Herschel, MMT, Magellan, and Palomar telescopes. For our adopted signal-to-noise ratio threshold on variability of broad Hβ emission, we find 17 new CLQs, yielding a confirmation rate of 20%. These candidates are at lower Eddington ratio relative to the overall quasar population, which supports a disk-wind model for the broad line region. Based on our sample, the CLQ fraction increases from 10% to roughly half as the continuum flux ratio between repeat spectra at 3420 increases from 1.5 to 6. We release a catalog of more than 200 highly variable candidates to facilitate future CLQ searches.
Autophagy is a lysosomal catabolic process essential to cell homeostasis and is related to the neuroprotection of the central nervous system. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid ...present in Cannabis sativa. Many therapeutic actions have been linked to this compound, including autophagy activation. However, the precise underlying molecular mechanisms remain unclear, and the downstream functional significance of these actions has yet to be determined. Here, we investigated CBD-evoked effects on autophagy in human neuroblastoma SH-SY5Y and murine astrocyte cell lines. We found that CBD-induced autophagy was substantially reduced in the presence of CB1, CB2 and TRPV1 receptor antagonists, AM 251, AM 630 and capsazepine, respectively. This result strongly indicates that the activation of these receptors mediates the autophagic flux. Additionally, we demonstrated that CBD activates autophagy through ERK1/2 activation and AKT suppression. Interestingly, CBD-mediated autophagy activation is dependent on the autophagy initiator ULK1, but mTORC1 independent. Thus, it is plausible that a non-canonical pathway is involved. Our findings collectively provide evidence that CBD stimulates autophagy signal transduction via crosstalk between the ERK1/2 and AKT kinases, which represent putative regulators of cell proliferation and survival. Furthermore, our study sheds light on potential therapeutic cannabinoid targets that could be developed for treating neurodegenerative disorders.
Power electronic-based wind turbine generators (WTGs) are capable of providing inertial response to the grid by releasing kinetic energy from the turbine blade; thus, as conventional power plants are ...retired, the reduction of online inertia can be compensated by designing frequency controls for the WTGs. Deployment of energy storage technology for renewable generations has been increased to have the renewables centralized with a system operator as an independent power supply by making up for their nature of generation. In addition, the cost of energy storage has dropped over time and global research activities on energy storage have been funded by private industries and governments. This paper investigates the opportunity of deploying an energy storage on a doubly fed induction generator (DFIG)-based WTG to respond to the system frequency, and then explores dynamic capabilities of the energy storage-embedded DFIG to boost its contribution while the frequency response is being provided by the power system's online inertia; thus, enabling an effective delivery of ancillary services to the system. To do this, the dynamic models of DFIG and energy storage are combined and simulated under the different operating conditions of a DFIG, such as subsynchronous, synchronous, and supersynchronous operations, using the PSCAD.
No single mechanism can account for the full amplitude of past atmospheric carbon dioxide (CO2) concentration variability over glacial-interglacial cycles. A build-up of carbon in the deep ocean has ...been shown to have occurred during the Last Glacial Maximum. However, the mechanisms responsible for the release of the deeply sequestered carbon to the atmosphere at deglaciation, and the relative importance of deep ocean sequestration in regulating millennial-timescale variations in atmospheric CO2 concentration before the Last Glacial Maximum, have remained unclear. Here we present sedimentary redox-sensitive trace-metal records from the Antarctic Zone of the Southern Ocean that provide a reconstruction of transient changes in deep ocean oxygenation and, by inference, respired carbon storage throughout the last glacial cycle. Our data suggest that respired carbon was removed from the abyssal Southern Ocean during the Northern Hemisphere cold phases of the deglaciation, when atmospheric CO2 concentration increased rapidly, reflecting--at least in part--a combination of dwindling iron fertilization by dust and enhanced deep ocean ventilation. Furthermore, our records show that the observed covariation between atmospheric CO2 concentration and abyssal Southern Ocean oxygenation was maintained throughout most of the past 80,000 years. This suggests that on millennial timescales deep ocean circulation and iron fertilization in the Southern Ocean played a consistent role in modifying atmospheric CO2 concentration.
Despite their factor of ∼108 difference in black hole mass, several lines of evidence suggest possible similarities between black hole accretion flows in active galactic nuclei (AGN) and Galactic ...X-ray binaries. However, it is still unclear whether the geometry of the disk-corona system in X-ray binaries directly scales up to AGN and whether this analogy still holds in different accretion states. We test this AGN/X-ray binary analogy by comparing the observed correlations between the UV-to-X-ray spectral index ( OX) and Eddington ratio in AGN to those predicted from observations of X-ray binary outbursts. This approach probes the geometry of their disk-corona systems as they transition between different accretion states. We use new Chandra X-ray and ground-based rest-UV observations of faded "changing-look" quasars to extend this comparison to lower Eddington ratios of <10−2, where observations of X-ray binaries predict a softening of OX in AGN. We find that the observed correlations between the OX and Eddington ratio of AGN displays a remarkable similarity to accretion state transitions in prototypical X-ray binary outbursts, including an inversion of this correlation at a critical Eddington ratio of ∼10−2. Our results suggest that the structures of black hole accretion flows directly scale across a factor of ∼108 in black hole mass and across different accretion states, enabling us to apply theoretical models of X-ray binaries to explain AGN phenomenology.
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