40 research outputs found
Post-translational modification directs nuclear and hyphal tip localization of Candida albicans mRNA-binding protein Slr1
The morphological transition of the opportunistic fungal pathogen Candida albicans from budding to hyphal growth has been implicated in its ability to cause disease in animal models. Absence of SR-like RNA-binding protein Slr1 slows hyphal formation and decreases virulence in a systemic candidiasis model, suggesting a role for post-transcriptional regulation in these processes. SR (serine–arginine)-rich proteins influence multiple steps in mRNA metabolism and their localization and function are frequently controlled by modification. We now demonstrate that Slr1 binds to polyadenylated RNA and that its intracellular localization is modulated by phosphorylation and methylation. Wildtype Slr1-GFP is predominantly nuclear, but also co-fractionates with translating ribosomes. The non-phosphorylatable slr1-6SA-GFP protein, in which six serines in SR/RS clusters are substituted with alanines, primarily localizes to the cytoplasm in budding cells. Intriguingly, hyphal cells display a slr1-6SA-GFP focus at the tip near the Spitzenkörper, a vesicular structure involved in molecular trafficking to the tip. The presence of slr1-6SA-GFP hyphal tip foci is reduced in the absence of the mRNA-transport protein She3, suggesting that unphosphorylated Slr1 associates with mRNA–protein complexes transported to the tip. The impact of SLR1 deletion on hyphal formation and function thus may be partially due to a role in hyphal mRNA transport
PenQuest Volume 5, Number 1
Table of Contents for this Volume:
Success by Shatney
Maria by Jane O’Neal
Intrusions by Mark McBride
The Mystery of the Back Porch Light by Nature Johnston
Truth and the Violin by Shatney
Corporate America by Julie Crowell
Pete’s Cafe by Nature Johnston
Geranium by Anne Benjamin
The Man Who Buried His Books by William Slaughter
Erasures by William Slaughter
Mind You and other poems by Kate Mathews
Coffee in the Tea Room by Kathleen O’Brien
The Children by Katharine Rodier
Sisters, Reclamation, Not Wanting to Say, “I Told You So,” But… by Kathleen O’Brien
Genetics by Kathleen O’Brien
The Anguish of Flames by Kathleen O’Brien
turning plows by Mark McBride
A Valediction for My Father by Jonathan Williams
Untitled by Mark Sablow
Artificial Portrait by Kevin Christenson
Untitled by Latrell Mickler
Untitled by Kevin Christenson
Galvanistic Ascension by Mark Grisham
Power Surge by Mark Grisham
Untitled by Lori Kirsbau
Are Health Care Professionals Prepared to Implement Human Papillomavirus Testing? A Review of Psychosocial Determinants of Human Papillomavirus Test Acceptability in Primary Cervical Cancer Screening
Background: Guidelines for cervical cancer screening have been updated to include human papillomavirus (HPV) testing, which is more sensitive compared to cytology in detecting cervical intraepithelial neoplasia. Because of its increased sensitivity, a negative HPV test is more reassuring for a woman that she is at low risk for precancerous cervical lesions than a negative Pap test. Prompted by the inadequate translation of HPV test-based screening guidelines into practice, we aimed to synthesize the literature regarding health care providers (HCPs) knowledge, attitudes, and practices related to HPV testing and the influence of psychosocial factors on HCPs acceptability of HPV testing in primary cervical cancer screening.
Materials and Methods: We searched MEDLINE, Embase, PsycINFO, CINAHL, Global Health, and Web of Science for journal articles from January 1, 1980 to July 25, 2018. A narrative synthesis of HCPs knowledge, attitudes, and practices related to HPV testing is provided. Informed by the Patient Pathway framework, we used deductive thematic analysis to synthesize the influence of psychosocial factors on HCPs acceptability of HPV testing.
Results: The most important HCP knowledge gaps are related to the superior sensitivity of the HPV test and age-specific guideline recommendations for HPV testing. Thirty to fifty percent of HCPs are not compliant with guideline recommendations for HPV testing, for example, screening at shorter intervals than recommended. Barriers, facilitators, and contradictory evidence of HCPs' acceptability of the HPV test are grouped by category: (1) factors related to the HCP; (2) patient intrinsic factors; (3) factors corresponding to HCP's practice environment; and (4) health care system factors.
Conclusions: HCP's adherence to guidelines for HPV testing in cervical cancer screening is suboptimal and could be improved by specialty organizations ensuring consistency across guidelines. Targeted educational interventions to address barriers of HPV test acceptability identified in this review may facilitate the translation of HPV testing recommendations into practice
Health System Enablers and Barriers to Continuity of Care for First Nations Peoples Living with Chronic Disease
Introduction: Failings in providing continuity of care following an acute event for a chronic disease contribute to care inequities for First Nations Peoples in Australia, Canada, and Aotearoa (New Zealand). Methods: A rapid narrative review, including primary studies published in English from Medline, Embase, PsycINFO, and Cochrane Central, concerning chronic diseases (cancer, cardiovascular disease, chronic kidney disease, diabetes, and related complications), was conducted. Barriers and enablers to continuity of care for First Nations Peoples were explored considering an empirical lens from the World Health Organization framework on integrated person-centred health services. Results: Barriers included a need for more community initiatives, health and social care networks, and coaching and peer support. Enabling strategies included care adapted to patients’ cultural beliefs and behavioural, personal, and family influences; continued and trusting relationships among providers, patients, and caregivers; and provision of flexible, consistent, adaptable care along the continuum. Discussion: The support and co-creation of care solutions must be a dialogical participatory process adapted to each community. Conclusions: Health and social care should be harmonised with First Nations Peoples’ cultural beliefs and family influences. Sustainable strategies require a co-design commitment for well-funded flexible care plans considering coaching and peer support across the lifespan
The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III
The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with
new instrumentation and new surveys focused on Galactic structure and chemical
evolution, measurements of the baryon oscillation feature in the clustering of
galaxies and the quasar Ly alpha forest, and a radial velocity search for
planets around ~8000 stars. This paper describes the first data release of
SDSS-III (and the eighth counting from the beginning of the SDSS). The release
includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap,
bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a
third of the Celestial Sphere. All the imaging data have been reprocessed with
an improved sky-subtraction algorithm and a final, self-consistent photometric
recalibration and flat-field determination. This release also includes all data
from the second phase of the Sloan Extension for Galactic Understanding and
Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars
at both high and low Galactic latitudes. All the more than half a million
stellar spectra obtained with the SDSS spectrograph have been reprocessed
through an improved stellar parameters pipeline, which has better determination
of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from
submitted version
The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey
The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic
data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data
release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median
z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar
spectra, along with the data presented in previous data releases. These spectra
were obtained with the new BOSS spectrograph and were taken between 2009
December and 2011 July. In addition, the stellar parameters pipeline, which
determines radial velocities, surface temperatures, surface gravities, and
metallicities of stars, has been updated and refined with improvements in
temperature estimates for stars with T_eff<5000 K and in metallicity estimates
for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars
presented in DR8, including stars from SDSS-I and II, as well as those observed
as part of the SDSS-III Sloan Extension for Galactic Understanding and
Exploration-2 (SEGUE-2).
The astrometry error introduced in the DR8 imaging catalogs has been
corrected in the DR9 data products. The next data release for SDSS-III will be
in Summer 2013, which will present the first data from the Apache Point
Observatory Galactic Evolution Experiment (APOGEE) along with another year of
data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at
http://www.sdss3.org/dr
Erratum: “The eighth data release of the Sloan Digital Sky Survey: first data from SDSS-III” (2011, ApJS, 193, 29)
Section 3.5 of Aihara et al. (2011) described various sources of systematic error in the astrometry of the imaging data of the Sloan Digital Sky Survey (SDSS). In addition to these sources of error, there is an additional and more serious error, which introduces a large systematic shift in the astrometry over a large area around the north celestial pole. The region has irregular boundaries but in places extends as far south as declination δ ≈ 41◦. The sense of the shift is that the positions of all sources in the affected area are offset by roughly 250 mas in a northwest direction. We have updated the SDSS online documentation to reflect these errors, and to provide detailed quality information for each SDSS field
Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial
Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma.
Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We
aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.
Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries.
Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the
minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and
had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were
randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical
apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to
100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a
maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h
for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to
allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients
who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable.
This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.
Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid
(5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated
treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the
tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18).
Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and
placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein
thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of
5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).
Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our
results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a
randomised trial
SDSS-III: Massive Spectroscopic Surveys of the Distant Universe, the Milky Way Galaxy, and Extra-Solar Planetary Systems
Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II),
SDSS-III is a program of four spectroscopic surveys on three scientific themes:
dark energy and cosmological parameters, the history and structure of the Milky
Way, and the population of giant planets around other stars. In keeping with
SDSS tradition, SDSS-III will provide regular public releases of all its data,
beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an
overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5
million massive galaxies and Lya forest spectra of 150,000 quasars, using the
BAO feature of large scale structure to obtain percent-level determinations of
the distance scale and Hubble expansion rate at z<0.7 and at z~2.5. SEGUE-2,
which is now completed, measured medium-resolution (R=1800) optical spectra of
118,000 stars in a variety of target categories, probing chemical evolution,
stellar kinematics and substructure, and the mass profile of the dark matter
halo from the solar neighborhood to distances of 100 kpc. APOGEE will obtain
high-resolution (R~30,000), high signal-to-noise (S/N>100 per resolution
element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars,
measuring separate abundances for ~15 elements per star and creating the first
high-precision spectroscopic survey of all Galactic stellar populations (bulge,
bar, disks, halo) with a uniform set of stellar tracers and spectral
diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars
with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to
detect giant planets with periods up to two years, providing an unprecedented
data set for understanding the formation and dynamical evolution of giant
planet systems. (Abridged)Comment: Revised to version published in The Astronomical Journa
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have
fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in
25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16
regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of
correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP,
while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in
Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium
(LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region.
Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant
enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the
refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa,
an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of
PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent
signals within the same regio