bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cationic Liposomes Extend the Immunostimulatory Effect of CpG Oligodeoxynucleotide against Burkholderia pseudomallei Infection in BALB/c Mice
Authors: Puangpetch Apichaya , Anderson Robert , Huang Yan Y. , Sermswan Rasana W. , Chaicumpa Wanpen , Sirisinha Stitaya , Wongratanacheewin Surasakdi 
Published: March 2012

ABSTRACTMelioidosis is a severe disease caused by the Gram-negative bacteriumBurkholderia pseudomallei. Previously we showed that pretreatment of mice with CpG oligodeoxynucleotide (CpG ODN) 2 to 10 days prior toB. pseudomalleichallenge conferred as high as 90% protection, but this window of protection was rather short. In the present study, we therefore aimed to prolong this protective window and to gain further insight into the mechanisms underlying the protection induced by CpG ODN againstB. pseudomalleiinfection. It was found that the CpG ODN incorporated with cationic liposomes (DOTAP) but not zwitterionic liposomes (DOPC) provided complete protection against bacterial challenge. Although marked elevation of gamma interferon (IFN-γ) was found in the infected animals 2 days postinfection, it was significantly lowered by the DOTAP-plus-CpG ODN pretreatment. When appropriately activated, the phagocytic index and oxidative burst responses of neutrophils appeared not to be elevated. However, macrophages from stimulated mice showed higher levels of nitric oxide production and exhibited higher levels of antimicrobial activities, judging from lower numbers of viable intracellular bacteria. Taken together, our results demonstrate that DOTAP can enhance the protective window period of CpG ODN to at least 30 days and provide 100% protection againstB. pseudomalleiinfection. The protective effect of DOTAP plus CpG ODN could provide an alternative approach to preventing this lethal infection, for which no vaccine is yet available.
Analysis of Defined Combinations of Monoclonal Antibodies in Anthrax Toxin Neutralization Assays and Their Synergistic Action
Authors: Ngundi Miriam M. , Meade Bruce D. , Little Stephen F. , Quinn Conrad P. , Corbett Cindi R. , Brady Rebecca A. , Burns Drusilla L. 
Published: March 2012

ABSTRACTAntibodies against the protective antigen (PA) component of anthrax toxin play an important role in protection against disease caused byBacillus anthracis. In this study, we examined defined combinations of PA-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. We observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. Synergistic toxin-neutralizing antibody interactions were examined in more detail. We found that one mechanism that can lead to antibody synergy is the bridging of PA monomers by one antibody, with resultant bivalent binding of the second antibody. These results may aid in optimal design of new vaccines and antibody therapies against anthrax.
Regulation of
ykrL
(
htpX
) by Rok and YkrK, a Novel Type of Regulator in Bacillus subtilis
Authors: Marciniak Bogumiła C. , Trip Hein , Fusetti Fabrizia , Kuipers Oscar P. 
Published: March 2012

ABSTRACT

Expression of
ykrL
of
Bacillus subtilis
, encoding a close homologue of the
Escherichia coli
membrane protein quality control protease HtpX, was shown to be upregulated under membrane protein overproduction stress. Using DNA affinity chromatography, two proteins were found to bind to the promoter region of
ykrL
: Rok, known as a repressor of competence and genes for extracytoplasmic functions, and YkrK, a novel type of regulator encoded by the gene adjacent to
ykrL
but divergently transcribed. Electrophoretic mobility shift assays showed Rok and YkrK binding to the
ykrL
promoter region as well as YkrK binding to the
ykrK
promoter region. Comparative bioinformatic analysis of the
ykrL
promoter regions in related
Bacillus
species revealed a consensus motif, which was demonstrated to be the binding site of YkrK. Deletion of
rok
and
ykrK
in a P
ykrL
-
gfp
reporter strain showed that both proteins are repressors of
ykrL
expression. In addition, conditions which activated P
ykrL
(membrane protein overproduction, dissipation of the membrane potential, and salt and phenol stress) point to the involvement of YkrL in membrane protein quality control.
Computational Reconstruction of Bole1a, a Representative Synthetic Hepatitis C Virus Subtype 1a Genome
Authors: Munshaw Supriya , Bailey Justin R. , Liu Lin , Osburn William O. , Burke Kelly P. , Cox Andrea L. , Ray Stuart C. 
Published: March 2012

ABSTRACTHepatitis C virus (HCV) research is hampered by the use of arbitrary representative isolates in cell culture and immunology. The most replicative isolatein vitrois a subtype 2a virus (JFH-1); however, genotype 1 is more prevalent worldwide and represents about 70% of infections in the United States, and genotypes differ from one another by 31% to 33% at the nucleotide level. For phylogenetic and immunologic analyses, viruses H77 and HCV-1 (both subtype 1a) are commonly used based on their historic importance. In an effort to rationally design a representative subtype 1a virus (Bole1a), we used Bayesian phylogenetics, ancestral sequence reconstruction, and covariance analysis on a curated set of 390 full-length human HCV 1a sequences from GenBank. By design, Bole1a contains variations present in widely circulating strains and matches more epitope-sized peptides in a full-genome comparison to subtype 1a isolates than any other sequence studied. Parallel analyses confirm that selected epitopes from the Bole1a genome were able to elicit a robust T cell response. In a proof of concept for infectivity, the envelope genes (E1 and E2) of Bole1a were expressed in an HIV pseudoparticle system containing HCV envelope genes and HIV nonenvelope genes with luciferase expression. The resulting Bole1a pseudoparticle robustly infected Hep3B cells. In this study, we demonstrate that a rationally designed, fully synthetic HCV genome contains representative epitopes and envelope genes that assemble properly and mediate entry into target cells.
Hepatitis E Virus Replication Requires an Active Ubiquitin-Proteasome System
Authors: Karpe Yogesh A. , Meng Xiang-Jin 
Published: March 2012

ABSTRACT
The mechanism of hepatitis E virus (HEV) replication remains largely unknown. Here we demonstrate that HEV replication requires an active ubiquitin-proteasome system and that proteasome inhibitors affect HEV replication, possibly by inhibition of viral transcription or/and translation without a significant effect on cellular translation. Overexpression of ubiquitin in inhibitor-treated cells partially reverses the inhibitor effect on HEV replication. The results suggest that HEV replication requires interactions with proteasome machinery, which could be a potential therapeutic target against HEV.
Abuse of medication during international football competition in 2010 – lesson not learned
Authors: Tscholl Philippe Matthias , Dvorak Jiri 
Published: March 2012

BackgroundThe use of medication in professional football has previously been shown to defy clinical guidelines.Materials and methodsPhysicians of the teams who participated at the 2010 FIFA World Cup provided the list of medications used by each player within the 72 h preceding every match.ResultsDuring the tournament 71.7% of all players took medication, and 60.3% (444 of 736 players) took painkilling agents at least once. Over a third of players (39.0%) took a painkilling agent before every game. More medications were used during the finals than during the qualifying round of matches (pool games) (0.87±0.09 vs 0.77±0.03, p<0.01). Players from North and South America took almost twice the number of medications than did players from other continents (1.18±0.08 vs 0.64±0.03; p<0.01).ConclusionThe use of medication reported by the team physicians in international football competition is increasing. Systematic use – medication for every match – appeared to be the norm in certain teams. This has implications for player health. These data encourage efforts to better understand, and to address, this potential disastrous practice in professional sports.
Geriatric consultation service in emergency department: how does it work?
Authors: Yuen Terry Man Yue , Lee Larry Lap Yip , Or Ikea Lai Chun , Yeung Kwai Lin , Chan Jimmy Tak Shing , Chui Catherine Pui Yuk , Kun Emily Wai Lin 
Published: March 2012

BackgroundHong Kong is having a significant prevalence of geriatric patients who usually require admission after presentation to the hospital through emergency departments. The geriatric consultation programme ‘We Care’ aims at lowering acute geriatric medical admission.ObjectivesThe study aims at analysing the impact of the geriatric consultation service on the acute medical admission, and to study the characteristics and outcome of geriatric patients.MethodsRetrospective study. Patients who received geriatric consultations during 1 January 2009 to 1 March 2011 were enrolled. The demographic information, diseases case mix, venue of discharge, clinical severity, community nursing service referrals and adverse outcomes were retrieved and analysed. The incidence of adverse outcomes under the presence of each factor was studied.Results2202 geriatric patients were referred. Their age ranged from 45 to 99 (mean 79.91, SD 7.45, median 80). These cases were categorised into: (1) chronic pulmonary disease (n=673; 30.6%), (2) debilitating cardiac disease (n=526; 23.9%), (3) geriatric syndromes (n=147; 6.7%), (4) neurological problems (n=416; 18.9%), (5) diabetes-related problems (n=146; 6.6%), (6) terminal malignancy (n=39; 1.8%), (7) electrolyte or input/output disturbance (n=137; 6.2%), (8) non-respiratory infections (n=36, 1.6%) and (9) others (n=82; 3.7%). Acute medical admission was evaded in 84.7% of all consultations with 1039 (47.2%) patients discharged home and 825 patients (37.5%) admitted to convalescent hospital. The incidence rate of adverse outcomes was 1.6%.ConclusionProgramme ‘We Care’ provided comprehensive geriatric assessment to suitable geriatric patients, resulting in an effective reduction of acute geriatric hospital admission.
Mesoproterozoic emplacement and enriched mantle derivation of the Racherla alkali syenite, Palaeo-Mesoproterozoic Cuddapah Basin, southern India: insights from
in situ
Sr–Nd isotopic analysis on apatite
Authors: Chalapathi Rao N. V. , Wu Fu-Yuan , Srinivas M. 
Published: March 2012

Abstract

We report an
in situ
Sm–Nd isochron age of 1326±73 Ma, determined by LA-MC-ICP-MS (laser ablation-multiple collector-inductively coupled plasma-mass spectrometry), on crystalline apatite grains from the Racherla alkali syenite occurring in the Palaeo-Mesoproterozoic Cuddapah Basin, southern India. The obtained Mesoproterozoic age necessitates the Racherla syenite to be an intrusive into the sedimentary rocks of the Cuddapah Basin contrary to some previous suggestion that it represents an inlier of the basement pluton. Age of the dated syenite, within its error limits, is also coeval with that of the nearby Chelima lamproite (1354±52 Ma) and other syenite complexes (
c
. 1352 Ma) located elsewhere within the Eastern Ghats Mobile Belt, southern India, thereby implying a common geotectonic control in all of their generation. Incompatible trace element signatures (high La/Nb, Zr/Nb and La/Yb),
87
Sr/
86
Sr (0.70432±10) and the lower Nd isotopic ratio (

ε

Nd
(t) −8.9) of the apatite suggest derivation of the Racherla syenite parent magma from an enriched mantle source. Our findings provide compelling evidence for the existence of ancient (
c
. 2.6 Ga) metasomatized lithospheric mantle, at the Archaean–Palaeoproterozoic boundary, beneath the Cuddapah Basin. This enriched mantle appears to have had played a dominant role in the generation of co-spatial and coeval lamproites within and around the Cuddapah Basin and a plethora of alkaline and sub-alkaline syenites within the Eastern Ghats Mobile Belt. Implications of our study in the context of Indo-Antarctic collisional tectonics are also explored.
Palaeoproterozoic sedimentation on the Singhbhum Craton: global context and comparison with Kaapvaal
Authors: Mazumder R. , Eriksson P. G. , De S. , Bumby A. J. , Lenhardt N. 
Published: March 2012

Abstract

The Singhbhum Craton has a limited Palaeoproterozoic supracrustal record, which suggests a three-part history, comprising: a long period of high freeboard and palaeosol formation on granitoids; subsequent rift-related mafic–ultramafic volcanism and subordinate sedimentation (
c.
2.25–2.1 Ga: Dhanjori and Jagannathpur basin-fills; possibly also Simlipal, Malangtoli and Ongarbira basin-fills), which overlapped locally with mafic soil formation; and a major regression at around 2.0 Ga. Following a long hiatus, the approximately 1.6 Ga Dhalbhum–Dalma succession was laid down, probably under continental conditions. This rather truncated record stands in contrast to the chronologically and geographically much more widespread supracrustal basin-fills of the Kaapvaal Craton, and there appears to be an overall poor comparison between these two early Precambrian crustal blocks. However, on Kaapvaal, three analogous events are identified: widespread approximately 2.2 Ga mafic volcanism, followed by a well-developed palaeosol and a major transgression prior to 2.05 Ga. The three shared events between the two cratons are compatible with the postulate of a global, approximate 2.45–2.2 Ga shutdown of magmatic and tectonic geodynamics, with the origin of the triumvirate directly reflecting its resumption again after about 2.2 Ga. We recognize here that a large diversity of views on Singhbhum's geodynamic history exists, predicated on a lack of precise geochronology and commonly poor outcrops, and the current hypotheses are presented with these factors in mind.
Low Rate of Production of Apolipoproteins B100 and AI in 2 Patients With Anderson Disease (Chylomicron Retention Disease)
Authors: Ouguerram Khadija , Zaïr Yassine , Kasbi-Chadli Fatima , Nazih Hassane , Bligny Dominique , Schmitz Jacques , Aparicio Thomas , Chétiveaux Maud , Magot Thierry , Aggerbeck Laurence P. , Samson-Bouma Marie Elisabeth , Krempf Michel 
Published: March 2012

Objective—

Anderson disease is a rare inherited lipid malabsorption syndrome associated with hypocholesterolemia and linked to
SAR1B
mutations. The aim of this article was to analyze the mechanisms responsible for the low plasma apolipoprotein Apo-B100 and Apo-AI in 2 patients with Anderson disease.

Methods and Results—

A primed constant infusion of
13
C-leucine was administered for 14 hours to determine the kinetics of lipoproteins. In the 2 patients, total cholesterol (77 and 85 mg/dL versus 155±32 mg/dL), triglycerides (36 and 59 versus 82±24 mg/dL), Apo-B100 (48 and 43 versus 71±5 mg/dL), and Apo-AI (47 and 62 versus 130±7 mg/dL) were lower compared with 6 healthy individuals. Very-low-density lipoprotein-B100 production rate of the patients was lower (4.08 and 5.52 mg/kg/day versus 12.96±2.88 mg/kg/day) as was the fractional catabolic rate (5.04 and 4.32 day
−1
versus 12.24±3.84 day
−1
). No difference was observed in intermediate-density lipoprotein-B100 and LDL-B100 kinetic data. The production rate of high-density lipoprotein Apo-AI was lower in the patients (7.92 and 8.64 versus 11.96±1.92 mg/kg/day) and the fractional catabolic rate was higher (0.38 and 0.29 versus 0.22±0.01 day
−1
).

Conclusion—
The low plasma Apo-B100 and Apo-AI concentrations in the patients with Anderson disease were mainly related to low rates of production.
Apolipoprotein E4 Domain Interaction Accelerates Diet-Induced Atherosclerosis in Hypomorphic Arg-61
Apoe
Mice
Authors: Eberlé Delphine , Kim Roy Y. , Luk Fu Sang , de Mochel Nabora Soledad Reyes , Gaudreault Nathalie , Olivas Victor R. , Kumar Nikit , Posada Jessica M. , Birkeland Andrew C. , Rapp Joseph H. , Raffai Robert L. 
Published: March 2012

Objectives—
Apolipoprotein (apo) E4 is an established risk factor for atherosclerosis, but the structural components underlying this association remain unclear. ApoE4 is characterized by 2 biophysical properties: domain interaction and molten globule state. Substituting Arg-61 for Thr-61 in mouse apoE introduces domain interaction without molten globule state, allowing us to delineate potential proatherogenic effects of domain interaction in vivo.

Methods and Results—

We studied atherosclerosis susceptibility of hypomorphic
Apoe
mice expressing either Thr-61 or Arg-61 apoE (
Apoe
T
h/h
or
Apoe
R
h/h
mice). On a chow diet, both mouse models were normolipidemic with similar levels of plasma apoE and lipoproteins. However, on a high-cholesterol diet,
Apoe
R
h/h
mice displayed increased levels of total plasma cholesterol and very-low-density lipoprotein as well as larger atherosclerotic plaques in the aortic root, arch, and descending aorta compared with
Apoe
T
h/h
mice. In addition, evidence of cellular dysfunction was identified in peritoneal
Apoe
R
h/h
macrophages which released lower amounts of apoE in culture medium and displayed increased expression of major histocompatibility complex class II molecules.

Conclusions—
These data indicate that domain interaction mediates proatherogenic effects of apoE4 in part by modulating lipoprotein metabolism and macrophage biology. Pharmaceutical targeting of domain interaction could lead to new treatments for atherosclerosis in apoE4 individuals.
Predicting the Risk of Symptomatic Intracerebral Hemorrhage in Ischemic Stroke Treated With Intravenous Alteplase
Authors: Mazya Michael , Egido José A. , Ford Gary A. , Lees Kennedy R. , Mikulik Robert , Toni Danilo , Wahlgren Nils , Ahmed Niaz 
Published: March 2012

Background and Purpose—
Symptomatic intracerebral hemorrhage (SICH) is a serious complication in patients with acute ischemic stroke treated with intravenous thrombolysis. We aimed to develop a clinical score that can easily be applied to predict the risk of SICH.

Methods—
We analyzed data from 31 627 patients treated with intravenous alteplase enrolled in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register. The outcome measure was SICH per the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) definition: a Type 2 parenchymal hemorrhage with deterioration in National Institutes of Health Stroke Scale score of ≥4 points or death. Univariate risk factors associated with the outcome were entered into a logistic regression model after stratification of continuous variables. Adjusted ORs for the independent risk factors were converted into points, which were summated to produce a risk score.

Results—
We identified 9 independent risk factors for SICH: baseline National Institutes of Health Stroke Scale, serum glucose, systolic blood pressure, age, body weight, stroke onset to treatment time, aspirin or combined aspirin and clopidogrel, and history of hypertension. The overall rate of SICH was 1.8%. The risk score ranged from 0 to 12 points and showed a >70-fold graded increase in the rate of SICH for patients with a score ≥10 points (14.3%) compared with a score of 0 point (0.2%). The prognostic discriminating capability by C statistic was 0.70.

Conclusions—
The SITS SICH risk score predicts large cerebral parenchymal hemorrhages associated with severe clinical deterioration. The score could aid clinicians to identify patients at high as well as low risk of SICH after intravenous alteplase.
A Study of Intraseasonal Temperature Variability in Southeastern South America
Authors: Naumann Gustavo , Vargas Walter M. 
Published: March 2012

Abstract
The main goal of this work was to conduct an intraseasonal climate variability analysis using wavelet and principal component analysis over a southeastern South American daily maximum and minimum temperature series from the end of the nineteenth until the beginning of the twenty-first century. The analysis showed that there is a definite and coherent signal in the intraseasonal maximum and minimum temperatures. The most noticeable signal was observed during the winter months. The frequency of the intraseasonal signal was more complex for the maximum temperature, and in some stations, it displayed a bimodal distribution. A defined pattern that described a coherent variability between 30 and 60 days throughout the entire region was observed. This pattern potentially allows classification of the regional variability and adjustments to the temperature forecasting models on a daily basis.
Finding the needle in the haystack: A review of microarray gene expression research into schizophrenia
Authors: Kumarasinghe Nishantha , Tooney Paul A , Schall Ulrich 
Published: March 2012

Background: With an estimated 80% heritability, molecular genetic research into schizophrenia has remained inconclusive. Recent large-scale, genome-wide association studies only identified a small number of susceptibility genes with individually very small effect sizes. However, the variable expression of the phenotype is not well captured in diagnosis-based research as well as when assuming a ‘heterogenic risk model’ (as apposed to a monogenic or polygenic model). Hence, the expression of susceptibility genes in response to environmental factors in concert with other disease-promoting or protecting genes has increasingly attracted attention. Method: The current review summarises findings of microarray gene expression research with relevance to schizophrenia as they emerged over the past decade. Results: Most findings from post mortem, peripheral tissues and animal models to date have linked altered gene expression in schizophrenia to presynaptic function, signalling, myelination, neural migration, cellular immune mechanisms, and response to oxidative stress consistent with multiple small effects of many individual genes. However, the majority of results are difficult to interpret due to small sample sizes (i.e. potential type-2 errors), confounding factors (i.e. medication effects) or lack of plausible neurobiological theory. Conclusion: Nevertheless, microarray gene expression research is likely to play an important role in the future when investigating gene/gene and gene/environment interactions by adopting a neurobiologically sound theoretical framework.
Clinical features of parricide in patients with schizophrenia
Authors: Ahn Byoung-Hoon , Kim Jeong-Hyun , Oh Sohee , Choi Sang Sub , Ahn Sung Ho , Kim Sun Bum 
Published: March 2012

Objective: This study aimed to investigate the factors associated with parricide in patients with schizophrenia who committed homicide. Method: Among patients with schizophrenia who were in the National Institute of Forensic Psychiatry between November and December 2007, 88 patients who committed homicides were enrolled; 59 had committed parricide, and 29 had killed strangers. Medical charts, written expert opinions, written records of police or prosecutors, and court decisions were reviewed. Direct interviews with patients were also conducted. Results: Significant factors associated with parricide among homicidal patients with schizophrenia were living with the victim, female sex of the victim, and offense-provoking events including scolding, threatening forced hospitalisation, and forcing medication on the patient before the homicide. Capgras syndrome was present at a significantly higher rate in the parricide group than in the stranger group. Drug compliance at the time of the offence was low in both groups. Conclusions: Untreated psychotic symptoms such as Capgras syndrome, living with elderly parents, especially mothers, and conflicts caused by victims’ scolding, threatening forced hospitalisation, and forcing medication on the patients are associated with parricide among homicide offenders with schizophrenia.