bluuebunny/crossref_metadata_2025_split huggingface dataset:
The 3-Hydroxy-Methylglutaryl Coenzyme A LyaseHCL1Is Required for Macrophage Colonization by Human Fungal Pathogen Histoplasma capsulatum
Authors: Isaac Dervla T. , Coady Alison , Van Prooyen Nancy , Sil Anita 
Published: November 2012

ABSTRACTHistoplasma capsulatumis a fungal respiratory pathogen that survives and replicates within the phagolysosome of macrophages. The molecular factors it utilizes to subvert macrophage antimicrobial defenses are largely unknown. Although the ability ofH. capsulatumto prevent acidification of the macrophage phagolysosome is thought to be critical for intracellular survival, this hypothesis has not been tested sinceH. capsulatummutants that experience decreased phagosomal pH have not been identified. In a screen to identifyH. capsulatumgenes required for lysis of bone marrow-derived macrophages (BMDMs), we identified an insertion mutation disrupting theH. capsulatumhomolog of 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) lyase (HCL1). In addition to its inability to lyse macrophages, thehcl1mutant had a severe growth defect in BMDMs, indicating that HMG CoA lyase gene function is critical for macrophage colonization. In other organisms, HMG CoA lyase catalyzes the last step in the leucine catabolism pathway. In addition, both fungi and humans deficient in HMG CoA lyase accumulate acidic intermediates as a consequence of their inability to catabolize leucine. Consistent with observations in other organisms, theH. capsulatumhcl1mutant was unable to grow on leucine as the major carbon source, caused acidification of its growth mediumin vitro, and resided in an acidified vacuole within macrophages. Mice infected with thehcl1mutant took significantly longer to succumb to infection than mice infected with the wild-type strain. Taken together, these data indicate the importance of Hcl1 function inH. capsulatumreplication in the harsh growth environment of the macrophage phagosome.
EptC of Campylobacter jejuni Mediates Phenotypes Involved in Host Interactions and Virulence
Authors: Cullen Thomas W. , O'Brien John P. , Hendrixson David R. , Giles David K. , Hobb Rhonda I. , Thompson Stuart A. , Brodbelt Jennifer S. , Trent M. Stephen 
Published: November 2012

ABSTRACT

Campylobacter jejuni
is a natural commensal of the avian intestinal tract. However, the bacterium is also the leading cause of acute bacterial diarrhea worldwide and is implicated in development of Guillain-Barré syndrome. Like many bacterial pathogens,
C. jejuni
assembles complex surface structures that interface with the surrounding environment and are involved in pathogenesis. Recent work in
C. jejuni
identified a gene encoding a novel phosphoethanolamine (pEtN) transferase, EptC (Cj0256), that plays a promiscuous role in modifying the flagellar rod protein, FlgG; the lipid A domain of lipooligosaccharide (LOS); and several
N
-linked glycans. In this work, we report that EptC catalyzes the addition of pEtN to the first heptose sugar of the inner core oligosaccharide of LOS, a fourth enzymatic target. We also examine the role pEtN modification plays in circumventing detection and/or killing by host defenses. Specifically, we show that modification of
C. jejuni
lipid A with pEtN results in increased recognition by the human Toll-like receptor 4–myeloid differentiation factor 2 (hTLR4-MD2) complex, along with providing resistance to relevant mammalian and avian antimicrobial peptides (i.e., defensins). We also confirm the inability of aberrant forms of LOS to activate Toll-like receptor 2 (TLR2). Most exciting, we demonstrate that strains lacking
eptC
show decreased commensal colonization of chick ceca and reduced colonization of BALB/cByJ mice compared to wild-type strains. Our results indicate that modification of surface structures with pEtN by EptC is key to its ability to promote commensalism in an avian host and to survive in the mammalian gastrointestinal environment.
Symmetry-adapted perturbation theory study for some magnesium complexes
Authors: Esrafili Mehdi D. , Yourdkhani Sirous 
Published: November 2012

A systematic theoretical study on Mg–ligand interactions has been carried out employing both ab initio correlated wave function and density functional methods. The interactions of the Mg(CH3N2)2moiety with BF, CO, N2, NH3, and H2O ligands have been investigated by performing calculations at the B3LYP, MP2, MP4, and CCSD(T)/6–311++G(3df,3pd) levels of theory. Results indicate that the interaction energies of the Mg(CH3N2)2–L complexes increase in the order NH3 > H2O > BF > CO > N2. Symmetry-adapted perturbation theory (SAPT) analysis has been carried out to understand the nature of the forces involved in the bonding. The SAPT results indicate that the stabilities of the Mg–L interactions are attributed mainly to electrostatic effects, while induction and dispersion forces also play a significant role. The evaluated SAPT interaction energies for the Mg(CH3N2)2–L complexes are generally in good agreement with those obtained using the supermolecule CCSD(T) methods, suggesting that SAPT is a proper method to study the intermolecular interactions in these complexes. The results also suggest an explanation for the unique role of Mg2+as a carrier of water molecules that mediate enzymatic hydrolysis reactions.
Palaeoecology and sedimentology of Carboniferous glacial and post-glacial successions in the Paganzo and Río Blanco basins of northwestern Argentina
Authors: Dineen A. A. , Fraiser M. L. , Isbell J. L. 
Published: November 2012

Abstract
Recent studies show that Late Palaeozoic Ice Age (LPIA) climate change broadly affected marine invertebrate faunas: glaciations decreased origination and extinction and long-term gradual global warming during the final deglaciation altered palaeocommunity composition. Carboniferous stratigraphy and palaeoecology in the Paganzo and Río Blanco basins of southwestern Gondwana (present-day Argentina) were studied in ordered to further determine how palaeocommunities were influenced by glacial and post-glacial processes during the LPIA. In the Paganzo Basin, the Guandacol Formation consisted of an ice-proximal to very ice-distal glaciomarine succession, while the Tupe Formation represented continental fluvial lowstand sedimentation interrupted by periodic marine incursions (estuary setting). In the Río Blanco Basin, the Río del Peñon Formation represents a shallowing-upwards coastal marine facies under the influence of wave and storm activity. Diversity and abundance data from northwestern Argentina reflects that ice-proximal environments proved physiologically stressful to organisms, limiting colonization to only opportunistic fauna. Following glaciation, the fauna of northwestern Argentina diversified and became increasingly ecologically complex during two marine transgressions in the Río Blanco Basin. It is interpreted that palaeocommunity establishment, composition and diversification in western Argentina during the LPIA was mostly dependent upon localized environmental conditions and palaeogeographic location.
Late Palaeozoic–Early Triassic deposition and climates between Samfrau and Tethys: A review
Authors: Wopfner H. 
Published: November 2012

Abstract
In the period between the Westphalian and the Early Triassic, climatic conditions across Gondwana changed from the Gondwana-wide glaciation in the Late Carboniferous–Early Permian to warm to hot, semi-humid to arid conditions by the Late Permian–Early Triassic. In Afro-Arabia, glaciers advanced to 40° palaeolatitude creating a steep gradient between them and the temperate-humid environment in the vicinity of the equator. Synchronous deglaciation associated with a eustatic rise of sea level in the Early Sakmarian was followed by a flattening of the climate gradient and increased humidity, expressed by blackwater rivers and coal swamps between the South Pole and about 50° palaeolatitude and increasing aridity towards the equator. Brief poleward advances of hot aridity are evident around the Kungurian. Expansion of the hot climate zone to the south took place in the Middle Permian, commencing with a humid to semi-humid phase in the south and semi-arid to arid conditions towards the north. A short pluvial event is locally indicated at the beginning of the Triassic, but warm semi-arid to semi-humid conditions prevailed in the south and hot aridity near the equator. There are variations of that general theme in eastern Gondwana, but the fundamental changes in climate-controlled depositional environments occurred almost synchronously over the whole of Gondwana, including Antarctica. The slight drift of Gondwana towards the equator is therefore an unlikely cause for these changes, as are modifications of ocean–continent geometries or of atmospheric composition. As the main driver was temperature it is suggested that governing control, not only of global temperature but also of the intensity of geotectonic activities, was imposed on the solar system by forces emanating from our galaxy (cosmic ray flux, magnetic intensity, gravitational vectors) and their variation over the course of a galactic year (the time for the solar system to orbit the core of the galaxy).
Carbon and oxygen isotope records of Permian brachiopods from relatively low and high palaeolatitudes: climatic seasonality and evaporation
Authors: Nielsen Jesper Kresten , BŁażejowski BŁażej , Gieszcz Piotr , Nielsen Jan Kresten 
Published: November 2012

Abstract

Several brachiopods which belong to the same genus
Horridonia
of late Early and early Late Permian age in Spitsbergen and Poland, respectively, have been petrographically and geochemically analysed to verify seasonal variation in stable carbon and oxygen isotope values for palaeoclimatological implications. The specimens of
Horridonia timanica
from Spitsbergen show distinct cyclicity reflective of seasonal pattern, while those of
Horridonia horrida
from Poland do not. These differences are explained by the fact that the former lived at high palaeolatitudes at the northern margin of the supercontinent Pangaea where the seawater temperature differences between winter and summer seasons were greater, as expressed in the isotopic composition of the skeletal materials. In contrast, the shell growth of
Horridonia horrida
was subjected to strong evaporative influence by climatic variations in the eastern area of Pangaea.
On the Simplex Algorithm Initializing
Authors: Stojković Nebojša V. , Stanimirović Predrag S. , Petković Marko D. , Milojković Danka S. 
Published: November 2012

This paper discusses the importance of starting point in the simplex algorithm. Three different methods for finding a basic feasible solution are compared throughout performed numerical test examples. We show that our two methods on the Netlib	test problems have better performances than the classical algorithm for finding initial solution. The comparison of the introduced optimization softwares is based on the number of iterative steps and on the required CPU time. It is pointed out that on average it takes more iterations to determine the starting point than the number of iterations required by the simplex algorithm to find the optimal solution.
Atrial Giant Cell Myocarditis
Authors: Larsen Brandon T. , Maleszewski Joseph J. , Edwards William D. , Cooper Leslie T. , Sobonya Richard E. , Thompson V. Eric , Duckett Simon G. , Peebles Charles R. , Simpson Iain A. , Tazelaar Henry D. 
Published: November 2012

Background—
Giant cell myocarditis (GCM) typically causes fulminant heart failure, arrhythmias, or heart block, necessitating aggressive immunosuppression, ventricular assist device insertion, or cardiac transplantation. We describe a novel variant of GCM, primarily involving the atria, that displays distinctive clinical features and follows a more benign course than ventricular GCM.

Methods and Results—
We identified 6 patients (median age 67.5 years, 4 male) with atrial GCM in our pathology consultation practices from 2010 to 2012. Clinical history, imaging, and pathology materials were reviewed. Clinically, 4 patients had atrial fibrillation, 1 had acute heart failure, and 1 had incidental disease at autopsy. Among the 5 living patients, echocardiography revealed severe atrial dilatation (5 cases), mitral/tricuspid regurgitation (5), atrial mural thrombus (3), atrial wall thickening (2), and atrial hypokinesis (2). Ventricular function was preserved in all 5. Histological review of surgically resected atria showed giant cell and lymphocytic infiltrates, lymphocytic myocarditis-like foci, cardiomyocyte necrosis, and cardiomyocyte hypertrophy in all cases. Other features included interstitial fibrosis (5), poorly-formed granulomas (4), eosinophils (4), neutrophils (1), and vasculitis (1). Treatment consisted of steroids and cyclosporine (1), pacemaker placement for sick sinus syndrome (1), and supportive care (3). All 5 living patients returned to baseline exercise tolerance after 6 to 16 weeks of follow-up.

Conclusions—
Atrial GCM represents a distinct clinicopathologic entity with a more favorable prognosis than classic ventricular GCM. This disorder should be included in the differential diagnosis of atrial dilatation, particularly when associated with atrial wall thickening. The utility of immunomodulatory therapy for this condition remains unknown.
Effect of Statins on Skeletal Muscle Function
Authors: Parker Beth A. , Capizzi Jeffrey A. , Grimaldi Adam S. , Clarkson Priscilla M. , Cole Stephanie M. , Keadle Justin , Chipkin Stuart , Pescatello Linda S. , Simpson Kathleen , White C. Michael , Thompson Paul D. 
Published: November 2012

Background—
Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied.

Methods and Results—

The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (
P
<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10;
P
=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (
P
=0.69).

Conclusions—
These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00609063.
Naturalistic Distraction and Driving Safety in Older Drivers
Authors: Aksan Nazan , Dawson Jeffrey D. , Emerson Jamie L. , Yu Lixi , Uc Ergun Y. , Anderson Steven W. , Rizzo Matthew 
Published: November 2012

Objective: In this study, we aimed to quantify and compare performance of middle-aged and older drivers during a naturalistic distraction paradigm (visual search for roadside targets) and to predict older drivers’ performance given functioning in visual, motor, and cognitive domains. Background: Distracted driving can imperil healthy adults and may disproportionally affect the safety of older drivers with visual, motor, and cognitive decline. Method: A total of 203 drivers, 120 healthy older (61 men and 59 women, ages 65 years and older) and 83 middle-aged drivers (38 men and 45 women, ages 40 to 64 years), participated in an on-road test in an instrumented vehicle. Outcome measures included performance in roadside target identification (traffic signs and restaurants) and concurrent driver safety. Differences in visual, motor, and cognitive functioning served as predictors. Results: Older drivers identified fewer landmarks and drove slower but committed more safety errors than did middle-aged drivers. Greater familiarity with local roads benefited performance of middle-aged but not older drivers. Visual cognition predicted both traffic sign identification and safety errors, and executive function predicted traffic sign identification over and above vision. Conclusion: Older adults are susceptible to driving safety errors while distracted by common secondary visual search tasks that are inherent to driving. The findings underscore that age-related cognitive decline affects older drivers’ management of driving tasks at multiple levels and can help inform the design of on-road tests and interventions for older drivers.
Prioritizing Pharmaceutical Activities
Authors: Renet Sophie , Tanguay Cynthia , Hall Kevin , Bussières Jean-François 
Published: November 2012

Objectives: The primary objective was to examine the consistency of prioritization decisions made by pharmacy residents in a simulated environment where the available resources are constrained. Secondary objectives were to rank the factors that influenced their prioritization and to compare the residents’ results with those of Canadian pharmacy leaders. Methods: We have developed a prioritization exercise that aims at evaluating how pharmaceutical activities are prioritized. The simulation was conducted with hospital pharmacy residents in 2 Quebec universities in 2011. Results: Residents covered a similar number of activities in the prioritization simulation (mean 27 of 32). Teams tended to favor a broad range of services delivered less comprehensively. Participants ranked “perception of the favorable impact of the activity on health outcomes” higher than “conclusive evidence available to support the decisions.” The relative weight attributed per domain was similar between pharmacy residents and pharmacy leaders, but their ranking of factors that influenced their decisions was different. Conclusions: Pharmacy residents opted to provide a wide range of services, but at a low level of comprehensiveness. The high variation between each team’s coverage per activity in this simulation supports the observation that pharmacy residents do not agree on a core set of pharmaceutical activities that should be prioritized.
Evaluation of Discontinuation of Atypical Antipsychotics Prescribed for ICU Delirium
Authors: Jasiak Karalea D. , Middleton Ellen A. , Camamo James M. , Erstad Brian L. , Snyder Linda S. , Huckleberry Yvonne C. 
Published: November 2012

A number of trials suggest that short-term use of atypical antipsychotics may be useful in the treatment of delirium associated with critical illness. However, long-term use of such agents for this indication has not been studied and may be associated with risks of adverse effects as well as unnecessary health care costs. A retrospective study of prescribing patterns of atypical antipsychotics initiated for the treatment of intensive care unit (ICU) delirium was performed to identify whether these agents were being discontinued prior to or upon hospital discharge. Of the 59 patients who met inclusion criteria and survived to hospital discharge, 28 (47%) were continued on the atypical antipsychotic upon discharge from the medical ICU. For those continued on the agent, 20 patients (71.4%) were prescribed continued therapy as an outpatient. Inpatient costs for atypical antipsychotics during the 9-month study period were increased by approximately $888. Annual cost of the medication as outpatient therapy is assessed at approximately $45 107. Although short-term trials of atypical antipsychotics may be useful for ICU delirium, caution is advised regarding potential adverse effects and added health care costs when use is prolonged.
A feasibility evaluation of oral pressure therapy for the treatment of obstructive sleep apnea
Authors: Farid-Moayer Mehran , Siegel Lawrence C. , Black Jed 
Published: November 2012

Objective: This feasibility study examined the initial-use safety and potential utility of a novel noninvasive oral pressure therapy (OPT) system designed to reduce airway obstruction during sleep. Methods: This was a single-center, proof-of-concept, single-treatment-night study in which subjects with obstructive sleep apnea (OSA) underwent a baseline polysomnography (PSG) study followed by PSG during use of an OPT system. The OPT system is composed of a bedside console, a polymer mouthpiece, and a flexible tube connecting the mouthpiece to the console. The console contains a pump that creates vacuum intended to pull the soft palate anteriorly and stabilize the tongue to reduce obstruction during sleep. Results: Fifty-four men and 17 women, aged 53.2 ± 11.5 years (mean ± SD) had a baseline apnea–hypopnea index (AHI) greater than 5 events per hour. OPT was generally well tolerated with no serious adverse events. OPT significantly decreased AHI from 34.4 ± 28.9 events per hour (mean ± SD) at baseline to 20.7 ± 23.3 ( p < 0.001). Treatment produced an AHI less than 10 in 48% of the subjects. OPT significantly improved oxygen desaturation index ( p < 0.001) and increased the percentage of the night with oxygen saturation of 90% or greater ( p = 0.028). Stage-N1 sleep shifts, total sleep-stage shifts, awakenings and the percentage of sleep time spent in N1 sleep were significantly reduced with treatment. Conclusion: This proof-of-concept study suggests that OPT can produce clinically relevant relief of OSA in certain subjects who are readily identified by PSG during trial use of the noninvasive system. OPT shows promise as a new treatment option for OSA in appropriate patients.