bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Glycosylphosphatidylinositol Anchor Is Required for Membrane Localization but Dispensable for Cell Wall Association of Chitin Deacetylase 2 in Cryptococcus neoformans
Authors: Gilbert Nicole M. , Baker Lorina G. , Specht Charles A. , Lodge Jennifer K. 
Published: February 2012

ABSTRACT

Cell wall proteins (CWPs) mediate important cellular processes in fungi, including adhesion, invasion, biofilm formation, and flocculation. The current model of fungal cell wall organization includes a major class of CWPs covalently bound to β-1,6-glucan via a remnant of a glycosylphosphatidylinositol (GPI) anchor. This model was established by studies of ascomycetes more than a decade ago, and relatively little work has been done with other fungi, although the presumption has been that proteins identified in the cell wall which contain a predicted GPI anchor are covalently linked to cell wall glucans. The pathogenic basidiomycete
Cryptococcus neoformans
encodes >50 putatively GPI-anchored proteins, some of which have been identified in the cell wall. One of these proteins is chitin deacetylase 2 (Cda2), an enzyme responsible for converting chitin to chitosan, a cell wall polymer recently established as a virulence factor for
C. neoformans
infection of mammalian hosts. Using a combination of biochemistry, molecular biology, and genetics, we show that Cda2 is GPI anchored to membranes but noncovalently associated with the cell wall by means independent of both its GPI anchor and β-1,6-glucan. We also show that Cda2 produces chitosan when localized to the plasma membrane, but association with the cell wall is not essential for this process, thereby providing insight into the mechanism of chitosan biosynthesis. These results increase our understanding of the surface of
C. neoformans
and provide models of cell walls likely applicable to other undercharacterized basidiomycete pathogenic fungi.

IMPORTANCE
The surface of a pathogenic microbe is a major interface with its host. In fungi, the outer surface consists of a complex matrix known as the cell wall, which includes polysaccharides, proteins, and other molecules. The mammalian host recognizes many of these surface molecules and mounts appropriate responses to combat the microbial infection.
Cryptococcus neoformans
is a serious fungal pathogen that kills over 600,000 people annually. It converts most of its chitin, a cell wall polysaccharide, to chitosan, which is necessary for virulence. Chitin deacetylase enzymes have been identified in the cell wall, and our studies were undertaken to understand how the deacetylase is linked to the wall and where it has activity. Our results have implications for the current model of chitosan biosynthesis and further challenge the paradigm of covalent linkages between cell wall proteins and polysaccharides through a lipid modification of the protein.
Deficiency in Mammalian Histone H2B Ubiquitin Ligase Bre1 (Rnf20/Rnf40) Leads to Replication Stress and Chromosomal Instability
Authors: Chernikova Sophia B. , Razorenova Olga V. , Higgins John P. , Sishc Brock J. , Nicolau Monica , Dorth Jennifer A. , Chernikova Diana A. , Kwok Shirley , Brooks James D. , Bailey Susan M. , Game John C. , Brown J. Martin 
Published: February 2012

Abstract
Mammalian Bre1 complexes (BRE1A/B (RNF20/40) in humans and Bre1a/b (Rnf20/40) in mice) function similarly to their yeast homolog Bre1 as ubiquitin ligases in monoubiquitination of histone H2B. This ubiquitination facilitates methylation of histone H3 at K4 and K79, and accounts for the roles of Bre1 and its homologs in transcriptional regulation. Recent studies by others suggested that Bre1 acts as a tumor suppressor, augmenting expression of select tumor suppressor genes and suppressing select oncogenes. In this study, we present an additional mechanism of tumor suppression by Bre1 through maintenance of genomic stability. We track the evolution of genomic instability in Bre1-deficient cells from replication-associated double-strand breaks (DSB) to specific genomic rearrangements that explain a rapid increase in DNA content and trigger breakage–fusion–bridge cycles. We show that aberrant RNA–DNA structures (R-loops) constitute a significant source of DSBs in Bre1-deficient cells. Combined with a previously reported defect in homologous recombination, generation of R-loops is a likely initiator of replication stress and genomic instability in Bre1-deficient cells. We propose that genomic instability triggered by Bre1 deficiency may be an important early step that precedes acquisition of an invasive phenotype, as we find decreased levels of BRE1A/B and dimethylated H3K79 in testicular seminoma and in the premalignant lesion in situ carcinoma. Cancer Res; 72(8); 2111–9. ©2012 AACR.
Second-Line Therapies in Hepatocellular Carcinoma: Emergence of Resistance to Sorafenib
Authors: Villanueva Augusto , Llovet Josep M. 
Published: February 2012

Abstract
Second-line therapies are needed for patients with advanced hepatocellular carcinoma who progress after sorafenib. Positive signals seen with brivanib in phase II studies, reported herein, have yet to be confirmed in phase III trials. Identification of the molecular mechanisms driving sorafenib resistance should guide drug development strategies in this setting. Clin Cancer Res; 18(7); 1824–6. ©2012 AACR.
Geographic Disparities in the Incidence and Outcomes of Hospitalized Myocardial Infarction
Authors: Yeh Robert W. , Normand Sharon-Lise T. , Wang Yun , Barr Christopher D. , Dominici Francesca 
Published: February 2012

Background—
Improvements in prevention have led to declines in incidence and mortality of myocardial infarction (MI) in selected populations. However, no studies have examined regional differences in recent trends in MI incidence, and few have examined whether known regional disparities in MI care have narrowed over time.

Methods and Results—

We compared trends in incidence rates of MI, associated procedures and mortality for all US Census Divisions (regions) in Medicare fee-for-service patients between 2000–2008 (292 773 151 patient-years). Two-stage hierarchical models were used to account for patient characteristics and state-level random effects. To assess trends in geographic disparities, we calculated changes in between-state variance for outcomes over time. Although the incidence of MI declined in all regions (
P
<0.001 for trend for each) between 2000–2008, adjusted rates of decline varied by region (annual declines ranging from 2.9–6.1%). Widening geographic disparities, as measured by percent change of between-state variance from 2000–2008, were observed for MI incidence (37.6% increase,
P
=0.03) and percutaneous coronary intervention rates (31.4% increase,
P
=0.06). Significant declines in risk-adjusted 30-day mortality were observed in all regions, with the fastest declines observed in states with higher baseline mortality rates.

Conclusions—
In a large contemporary analysis of geographic trends in MI epidemiology, the incidence of MI and associated mortality declined significantly in all US Census Divisions between 2000–2008. Although geographic disparities in MI incidence may have increased, regional differences in MI-associated mortality have narrowed.
Effect of Aspirin Versus Clopidogrel on Walking Exercise Performance in Intermittent Claudication—A Double‐Blind Randomized Multicenter Trial
Authors: Singer Elisabeth , Imfeld Stephan , Staub Daniel , Hoffmann Ulrich , Buschmann Ivo , Labs Karl‐Heinz , Jaeger Kurt A. ,   on behalf of the Arteriogenesis Competence Network Trialists' Group
Published: February 2012

Background
This study sought to determine possible effects of different antiplatelet therapies on walking exercise performance in intermittent claudication. Aspirin, in contrast to clopidogrel, interferes with processes that increase collateral conductance in an ischemic animal model.

Methods and Results

Patients with stable intermittent claudication were recruited from 21 centers in Switzerland and Germany and randomized to either aspirin or clopidogrel treatment. They participated in a 3‐month rehabilitation program (electronically monitored, home‐based, 1‐hour daily walking sessions at a speed of approximately 120 steps/min). Walking distance was assessed by treadmill tests (3.2 km/h; 12% grade) at baseline and after 12 weeks. A total of 229 of 259 patients with a mean age of 66.2±7.7 years completed the study according to the protocol. A total of 24.5% were females, 20.1% diabetics, and 85.6% were active/ex‐smokers. The baseline characteristics were a median (interquartile range) ankle/brachial index of 0.69 (0.57±0.8), an initial claudication distance (ICD) of 98 m (70 to 151 m), and an absolute claudication distance (ACD) of 162 m (113 to 302 m). Training resulted in a median increase of initial claudication distance by 33.5 m (33.3%) in the clopidogrel group and 29 m (33.9%) in the aspirin group. The values for absolute claudication distance were 60.5 m (34.9%) and 75 m (35.3%), respectively (p
ICD
=0.42 and p
ACD
=0.66).

Conclusions
Treatment with aspirin did not show a difference in initial claudication distance or absolute claudication distance improvements compared with clopidogrel after a 3‐month walking rehabilitation program.

Clinical Trial Registration

URL:
http://www.ClinicalTrials.gov
. Unique identifier: NCT00189618, URL:
http://EudraCT.ema.europa.eu
, Unique identifier: 2004‐005041‐35
A Global Approach to Assess the Potential Impact of Climate Change on Stream Water Temperatures and Related In-Stream First-Order Decay Rates
Authors: Punzet Manuel , Voß Frank , Voß Anja , Kynast Ellen , Bärlund Ilona 
Published: February 2012

Abstract
Stream water temperature is an important factor used in water quality modeling. To estimate monthly stream temperature on a global scale, a simple nonlinear regression model was developed. It was applied to stream temperatures recorded over a 36-yr period (1965–2001) at 1659 globally distributed gauging stations. Representative monthly air temperatures were obtained from the nearest grid cell included in the new global meteorological forcing dataset—the Water and Global Change (WATCH) Forcing Data. The regression model reproduced monthly stream temperatures with an efficiency of fit of 0.87. In addition, the regression model was applied for different climate zones (polar, snow, warm temperate arid, and equatorial climates) based on the Köppen–Geiger climate classification. For snow, warm temperate, and arid climates the efficiency of fit was larger than 0.82 including more than 1504 stations (90% of all records used). Analyses of heat-storage effects (seasonal hysteresis) did not show noticeable differences between the warming/cooling and global regression curves, respectively. The maximum difference between both limbs of the hysteresis curves was 1.6°C and thus neglected in the further analysis of the study. For validation purposes time series of stream temperatures for five individual river basins were computed applying the global regression equation. The accuracy of the global regression equation could be confirmed. About 77% of the predicted values differed by 3°C or less from measured stream temperatures. To examine the impact of climate change on stream water temperatures, gridded global monthly stream temperatures for the climate normal period (1961–90) were calculated as well as stream temperatures for the A2 and B1 climate change emission scenarios for the 2050s (2041–70). On average, there will be an increase of 1°–4°C in monthly stream temperature under the two climate scenarios. It was also found that in the months December, January, and February a noticeable warming predominantly occurs along the equatorial zone, while during the months June, July, and August large-scale or large increases can be observed in the northern and southern temperate zones. Consequently, projections of decay rates show a similar seasonal and spatial pattern as the corresponding stream temperatures. A regional increase up to ~25% could be observed. Thus, to ensure sufficient water quality for human purposes, but also for freshwater ecosystems, sustainable management strategies are required.
Rising to the human rights challenge in compulsory treatment – new approaches to mental health law in Australia
Authors: Callaghan Sascha , Ryan Christopher J 
Published: February 2012

Objective: To analyse, and explain to Australasian psychiatrists, recent proposed changes to the terms of coercive treatment for mental illness in Tasmania and Victoria and to place the proposals in the context of a broader human rights framework that is likely to impact the future shape of mental health legislation more generally. Methods: The Australian law reform proposals are reviewed against the requirements of numerous human rights instruments, including the recently ratified United Nations Convention on the Rights of Persons with Disabilities. Ethical and legal arguments are made to support the proposed changes and to introduce others, taking into account academic commentary on mental health law and recent empirical work on the ability to usefully categorise patients by their likelihood of harm to self and others. Results: The Victorian and Tasmanian draft mental health bills propose a new basis for compulsory psychiatric treatment in Australasia. If they become law, coercive psychiatric treatment could only be applied to patients who lack decision-making capacity. The Tasmanian draft bill also sets a new benchmark for timely independent review of compulsory treatment. However both jurisdictions propose to retain an ‘additional harm’ test which must be satisfied before patients may be treated without consent. This differs from non-psychiatric cases, where if patients are unable to consent to medical treatment for themselves, they will be entitled to receive coercive treatment if it is in their best interests. Conclusions: The proposed changes under the Tasmanian and Victorian draft mental health bills will ensure that, in line with local and international human rights obligations, only patients who lack decision-making capacity may be coercively treated for mental illness. However the continuing ‘additional harm’ criteria may breach human rights obligations by imposing a discriminatory threshold for care on patients who are unable to consent to treatment for themselves. This could be avoided by replacing the ‘additional harm’ test with a ‘best interests’ test.
How safe is the use of herbal weight-loss products sold over the Internet?
Authors: Ozdemir B , Sahin I , Kapucu H , Celbis O , Karakoc Y , Erdogan S , Onal Y 
Published: February 2012

Background: In recent years, the use of herbal weight-loss products sold over the Internet has rapidly increased; however, the safety of these products has not been well documented yet. More importantly, the declared ingredients in these products could be different than the marketed contents. Methods: Nine different herbal weight-loss products sold over the Internet were obtained. The ingredients of each product were analyzed in the Laboratory of Forensic Medicine and the Scientific and Technological Research Laboratory of Inonu University. Results: Although all studied weight-loss products were presented as pure herbal, three of them contain sibutramine, three contain caffeine, and three contain caffeine + temazepam. The amount of sibutramine in each capsule was found to be over 10 mg. We analyzed toxic and trace element levels of nine herbal products and found that these herbal products, even in low amounts, contain Pb, Al, Ni, and Ba. Conclusions: Our results indicate that herbal weight-loss products available without prescription and claimed to be purely herbal may contain pharmaceutical substances like sibutramine or temazepam in high doses. Moreover, they also may become contaminated with toxic metals. Since people commonly use these products unaware of its real constituents and without the suggestion or control of a physician, they might cause various health problems some of which might be harmful. Strict legal rules and control mechanisms must be established to minimize their possible harmful effects.
Increased expression of ER stress- and hypoxia-associated molecules in grey matter lesions in multiple sclerosis
Authors: McMahon JM , McQuaid S , Reynolds R , FitzGerald UF 
Published: February 2012

Background: The endoplasmic reticulum (ER) stress pathway may play a role in the pathogenesis multiple sclerosis (MS), and while ER stress-associated molecules have been demonstrated in white matter (WM) lesions, these have not been analysed in grey matter (GM) demyelination. Objective: The objective was to characterise the type and frequency of GM lesions and establish expression profiles of ER stress- and hypoxia-associated markers. Methods: Sections from 16 MS cases and 12 non-MS controls were stained for ER stress molecules (BiP and CHOP) and hypoxia-associated D110 antigen. Results: Of the GM lesions analysed, 24% were type 1 (continuous between GM and WM), 22% were type 2 (entirely within GM) and the majority (54%) were type 3 (extending from pia mater). Comparison of GM lesions, MS normal-appearing grey matter (NAGM) and non-MS control tissue showed that NAGM, type 1 and type 3 lesions all had significantly increased levels of CHOP compared to controls. According to morphological and dual-labelling criteria, the majority of CHOP-positive cells were microglia. Approximately 50% of GM lesions contained D110-positive cells. Conclusion: These data suggest that ER stress plays an important role in GM lesion development and may be critical in activation of microglia in pre-lesional NAGM. The high number of lesions containing D110-positive cells suggests a role for hypoxic-like insult in GM lesion development.
Parametric vs. Non-Parametric Statistics of Low Resolution Electromagnetic Tomography (LORETA)
Authors: Thatcher R. W. , North D. , Biver C. 
Published: February 2012

This study compared the relative statistical sensitivity of non-parametric and parametric statistics of 3-dimensional current sources as estimated by the EEG inverse solution Low Resolution Electromagnetic Tomography (LORETA). One would expect approximately 5% false positives (classification of a normal as abnormal) at the P < .025 level of probability (two tailed test) and approximately 1% false positives at the P < .005 level. EEG digital samples (2 second intervals sampled 128 Hz, 1 to 2 minutes eyes closed) from 43 normal adult subjects were imported into the Key Institute's LORETA program. We then used the Key Institute's cross-spectrum and the Key Institute's LORETA output files (*.lor) as the 2,394 gray matter pixel representation of 3-dimensional currents at different frequencies. The mean and standard deviation *.lor files were computed for each of the 2,394 gray matter pixels for each of the 43 subjects. Tests of Gaussianity and different transforms were computed in order to best approximate a normal distribution for each frequency and gray matter pixel. The relative sensitivity of parametric vs. non-parametric statistics were compared using a “leave-one-out” cross validation method in which individual normal subjects were withdrawn and then statistically classified as being either normal or abnormal based on the remaining subjects. Log10 transforms approximated Gaussian distribution in the range of 95% to 99% accuracy. Parametric Z score tests at P < .05 cross-validation demonstrated an average misclassification rate of approximately 4.25%, and range over the 2,394 gray matter pixels was 27.66% to 0.11%. At P < .01 parametric Z score cross-validation false positives were 0.26% and ranged from 6.65% to 0% false positives. The non-parametric Key Institute's t-max statistic at P < .05 had an average misclassification error rate of 7.64% and ranged from 43.37% to 0.04% false positives. The non-parametric t-max at P < .01 had an average misclassification rate of 6.67% and ranged from 41.34% to 0% false positives of the 2,394 gray matter pixels for any cross-validated normal subject. In conclusion, adequate approximation to Gaussian distribution and high cross-validation can be achieved by the Key Institute's LORETA programs by using a log10 transform and parametric statistics, and parametric normative comparisons had lower false positive rates than the non-parametric tests.
Cognitive Impairment in Major Depressive Disorder Revealed by Event-Related Potential N270
Authors: Mao Wei , Wang Yuping , Wang Dequan 
Published: February 2012

Major depressive disorder (MDD) is a mood disorder that is often accompanied by the impairment of cognitive functions. The aim of this study was to investigate the feasibility of N270 as an index for evaluating the cognitive impairment in MDD patients. Twenty-five patients with MDD diagnosed according to DSM-IV and 25 age matched normal controls performed a matching task while event-related potentials (ERPs) were recorded from their scalp. There were two kinds of stimulus pairs in this study: match condition, the second stimulus (S2) in a pair was identical to the first one (S1); mismatch condition, S2 conflicted with S1 in the color attribute. Subjects were required to press a button in the match condition and to press another button in the mismatch condition. A negative ERP component, N270, which was considered to reflect conflict processing activity in human brain, was evoked by S2 of the mismatch condition. The patient group showed a delayed and smaller N270 than the control group. The prolongation of its peak latency was significant at P3 and P4 electrodes, and the reduction of its peak amplitude was significant at F3, F4, P3 and P4 electrodes. The amplitude of P300 elicited in the match condition was decreased in the patient group at P3 and P4 electrodes, but its latency did not differ from the control group. The results indicate that MDD patients as a group showed cognitive decline. N270 is a sensitive index in revealing cognitive impairment.
Approximate Entropy in the Electroencephalogram during Wake and Sleep
Authors: Burioka Naoto , Miyata Masanori , Cornélissen Germaine , Halberg Franz , Takeshima Takao , Kaplan Daniel T. , Suyama Hisashi , Endo Masanori , Maegaki Yoshihiro , Nomura Takashi , Tomita Yutaka , Nakashima Kenji , Shimizu Eiji 
Published: February 2012

Entropy measurement can discriminate among complex systems, including deterministic, stochastic and composite systems. We evaluated the changes of approximate entropy (ApEn) in signals of the electroencephalogram (EEG) during sleep. EEG signals were recorded from eight healthy volunteers during nightly sleep. We estimated the values of ApEn in EEG signals in each sleep stage. The ApEn values for EEG signals (mean ± SD) were 0.896 ± 0.264 during eyes-closed waking state, 0.738 ± 0.089 during Stage I, 0.615 ± 0.107 during Stage II, 0.487 ± 0.101 during Stage III, 0.397 ± 0.078 during Stage IV and 0.789 ± 0.182 during REM sleep. The ApEn values were found to differ with statistical significance among the six different stages of consciousness (ANOVA, p<0.001). ApEn of EEG was statistically significantly lower during Stage IV and higher during wake and REM sleep. We conclude that ApEn measurement can be useful to estimate sleep stages and the complexity in brain activity.