bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined treatment with recombinant tissue plasminogen activator and dexamethasone phosphate‐containing liposomes improves neurological outcome and restricts lesion progression after embolic stroke in rats
Authors: Tiebosch Ivo A. C. W. , Crielaard Bart J. , Bouts Mark J. R. J. , Zwartbol René , Salas‐Perdomo Angelica , Lammers Twan , Planas Anna M. , Storm Gert , Dijkhuizen Rick M. 
Published: October 2012

AbstractVariable efficacies have been reported for glucocorticoid drugs as anti‐inflammatory treatment after stroke. We applied an alternative drug delivery strategy, by injection of dexamethasone phosphate‐containing liposomes in combination with recombinant tissue plasminogen activator (rtPA), in an experimental stroke model, and tested the hypothesis that this approach improves behavioral recovery and reduces lesion growth. Rats were subjected to right middle cerebral artery occlusion with a blood clot. After 2 h, animals were intravenously injected with rtPA plus empty long‐circulating liposomes (LCL), free dexamethasone phosphate (DXP), or DXP‐containing LCL (LCL‐DXP). Neurological status was evaluated with different behavioral tests up to 7 days after stroke. Lesion development was assessed by magnetic resonance imaging of tissue and perfusion parameters from 0–2 h until 7 days after stroke. Expression of brain inflammatory markers was measured with RT‐PCR at post‐stroke day 7. Treatment with rtPA plus LCL‐DXP resulted in significantly improved behavioral outcome as compared to treatment with rtPA plus empty LCL or free DXP. Acute and final brain lesion sizes were comparable between treatment groups; however a predictive algorithm revealed a significantly larger salvaged tissue area after treatment with LCL‐DXP. We conclude that delivery of dexamethasone phosphate via LCL in combination with rtPA‐induced thrombolysis can significantly improve outcome after stroke. Furthermore, magnetic resonance imaging‐based predictive algorithms provide a sensitive means to measure treatment effects on lesion development.
The inhibitory effect of S‐nitrosoglutathione on blood–brain barrier disruption and peroxynitrite formation in a rat model of experimental stroke
Authors: Khan Mushfiquddin , Dhammu Tajinder S. , Sakakima Harutoshi , Shunmugavel Anadakumar , Gilg Anne G. , Singh Avtar K. , Singh Inderjit 
Published: October 2012

AbstractThe hallmark of stroke injury is endothelial dysfunction leading to blood–brain barrier (BBB) leakage and edema. Among the causative factors of BBB disruption are accelerating peroxynitrite formation and the resultant decreased bioavailability of nitric oxide (NO). S‐nitrosoglutathione (GSNO), an S‐nitrosylating agent, was found not only to reduce the levels of peroxynitrite but also to protect the integrity of BBB in a rat model of cerebral ischemia and reperfusion (IR). A treatment with GSNO (3 μmol/kg) after IR reduced 3‐nitrotyrosine levels in and around vessels and maintained NO levels in brain. This mechanism protected endothelial function by reducing BBB leakage, increasing the expression of Zonula occludens‐1 (ZO‐1), decreasing edema, and reducing the expression of matrix metalloproteinase‐9 and E‐selectin in the neurovascular unit. An administration of the peroxynitrite‐forming agent 3‐morpholino sydnonimine (3 μmol/kg) at reperfusion increased BBB leakage and decreased the expression of ZO‐1, supporting the involvement of peroxynitrite in BBB disruption and edema. Mechanistically, the endothelium‐protecting action of GSNO was invoked by reducing the activity of nuclear factor kappa B and increasing the expression of S‐nitrosylated proteins. Taken together, the results support the ability of GSNO to improve endothelial function by reducing nitroxidative stress in stroke.
L1 Cell Adhesion Molecule Signaling Is Inhibited by Ethanol In Vivo
Authors: Littner Yoav , Tang Ningfeng , He Min , Bearer Cynthia F. 
Published: October 2012

BackgroundFetal alcohol spectrum disorder is an immense public health problem. In vitro studies support the hypothesis that L1 cell adhesion molecule (L1) is a target for ethanol (EtOH) developmental neurotoxicity. L1 is critical for the development of the central nervous system. It functions through signal transduction leading to phosphorylation and dephosphorylation of tyrosines on its cytoplasmic domain. The function of L1 is also dependent on trafficking through lipid rafts (LRs). Our hypothesis is that L1 is a target for EtOH neurotoxicity in vivo. Our objective is to demonstrate changes in L1 phosphorylation/dephosphorylation and LR association in vivo.MethodsRat pups on postnatal day 6 are administered 4.5, 5.25, and 6 g/kg of EtOH divided into 2 doses 2 hours apart, then killed. Cerebella are rapidly frozen for assay. Blood is analyzed for blood EtOH concentration. L1 tyrosine phosphorylation is determined by immunoprecipitation and dephosphorylation of tyrosine 1176 determined by immunoblot. LRs are isolated by sucrose density gradient, and the distribution of L1 in LRs is determined.ResultsEtOH at all doses reduced the relative amount of Y1176 dephosphorylation as well as the relative amount of L1 phosphorylated on other tyrosines. The proportion of L1 present in LRs is significantly increased in pups who received 6 g/kg EtOH compared to intubated controls.ConclusionsL1 is a target for EtOH developmental neurotoxicity in vivo.
Testing a Model of Depression Among Thai Adolescents
Authors: Vatanasin Duangjai , Thapinta Darawan , Thompson Elaine Adams , Thungjaroenkul Petsunee 
Published: October 2012

ProblemThis predictive correlational study was designed to test a comprehensive model of depression for Thai adolescents.MethodsThis sample included 800 high school students in Chiang Mai, Thailand. Data were collected using self‐reported measures of depression, negative automatic thoughts, effective social problem solving, ineffective social problem solving, rumination, parental care, parental overprotection, and negative life events.FindingsStructural equation modeling revealed that negative automatic thoughts, effective and ineffective social problem solving mediated the effects of rumination, negative life events, and parental care and overprotection on adolescent depression.ConclusionThese findings provide new knowledge about identified factors and the mechanisms of their influence on depression among Thai adolescents, which are appropriate for targeting preventive interventions.
Oxidative stress markers are not associated with outcomes after pediatric heart surgery
Authors: Manso Paulo H. , Carmona Fabio , Dal‐Pizzol Felipe , Petronilho Fabrícia , Cardoso Fabíola , Castro Margaret , Carlotti Ana P. C. P. 
Published: October 2012

SummaryObjectivesTo investigate whether perioperative serum levels of oxidative stress markers, thiobarbituric acid reactive substances (TBARS), and carbonyl moieties are associated with outcomes in children after heart surgery.BackgroundOxidative stress markers are increased following heart surgery with cardiopulmonary bypass (CPB) and can play a role in ischemia–reperfusion injury, but its associations with myocardial dysfunction, low cardiac output syndrome (LCOS), and outcomes are not proven.MethodsIn a retrospective secondary analysis of a cohort study comprising 55 children (median age, 109 [2–611] days), we compared pre‐, intra‐ and postoperative serum levels of TBARS and carbonyl moieties among patients with and without postoperative LCOS, cyanotic and acyanotic congenital heart disease (CHD), and survivors and nonsurvivors. We also assessed the independent effect of TBARS and carbonyl moieties peak levels on the mortality‐adjusted hospital length of stay (aLOS).ResultsPatients who developed postoperative LCOS (n = 36) were significantly younger, more frequently cyanotic, more severely ill, and underwent more complex procedures with longer CPB. However, TBARS and carbonyl moieties serum levels did not change significantly over time. Moreover, they were not significantly different in patients with or without LCOS, cyanotic and acyanotic CHD, or survivors and nonsurvivors. There was a significant correlation between TBARS and tumor necrosis factor alpha (TNF‐α) peak serum levels. Neither TBARS nor carbonyl moieties peak serum levels were independently associated with aLOS.ConclusionsIn conclusion, oxidative stress markers TBARS and carbonyl moieties were not associated with the development of LCOS, the aLOS, or mortality in children after heart surgery with CPB.
Improving On‐time starts for patients scheduled with general anesthesia in a MRI suite
Authors: Mahmoud Mohamed A. , Koch Bernadette L. , Jones Blaise V. , Varughese Anna M. 
Published: October 2012

SummaryObjectiveWe applied quality improvement methodology to identify unnecessary, redundant parts of processes that can lead to delayed on‐time starts for patients scheduled with general anesthesia (GA) in the radiology department.AimTo address the issue of delayed on‐time starts by improving work flow for the first patient scheduled with GA.BackgroundUnplanned imaging in a high‐volume MRI suite can result in a significant ripple effect throughout the day. Delayed on‐time starts can lead to patient, family, and staff dissatisfaction due to significant wait times.Materials and methodsThe team conducted a 5 month improvement project. Baseline data were obtained from pilot time studies allowed the team to identify reasons why the first case was not starting on time and to identify several key drivers to improve the process. Using the framework of small tests of change or the Plan‐Do‐Study‐Act model, our key interventions primarily focused on standardizing the processes for completing the preimaging evaluation and for anesthesia induction. The primary objective measure of successful on‐time start was defined as obtaining the first MRI image within 10 min of the scheduled start time, for the first patients of the day scheduled with GA. The secondary outcome measure was the extent of the delay quantified in minutes.ResultsPrior to the initiation of the project, only 36% of the first patients scheduled with GA each day met the primary objective measure. At the conclusion of the project 84% started on time. The secondary measure also showed significant improvement.ConclusionsProcess improvement projects in anesthesia can yield positive results, using small incremental standardized changes. We used a quality improvement methods to successfully improve on‐time start for patients scheduled with GA in high‐volume MRI suite.
Genetic Diversity of Clinical and Environmental Vibrio parahaemolyticus Strains from the Pacific Northwest
Authors: Paranjpye Rohinee , Hamel Owen S. , Stojanovski Asta , Liermann Martin 
Published: October 2012

ABSTRACT

Since 1997, cases of
Vibrio parahaemolyticus
-related gastroenteritis from the consumption of raw oysters harvested in Washington State have been higher than historical levels. These cases have shown little or no correlation with concentrations of potentially pathogenic
V. parahaemolyticus
(positive for the thermostable direct hemolysin gene,
tdh
) in oysters, although significant concentrations of
tdh
+
V. parahaemolyticus
strains were isolated from shellfish-growing areas in the Pacific Northwest (PNW). We compared clinical and environmental strains isolated from the PNW to those from other geographic regions within the United States and Asia for the presence of virulence-associated genes, including the thermostable direct hemolysin (
tdh
), the thermostable-related hemolysin (
trh
), urease (
ureR
), the pandemic group specific markers
orf8
and
toxRS
, and genes encoding both type 3 secretion systems (T3SS1 and T3SS2). The majority of clinical strains from the PNW were positive for
tdh
,
trh
, and
ureR
genes, while a significant proportion of environmental isolates were
tdh
+
but
trh
negative. Hierarchical clustering grouped the majority of these clinical isolates into a cluster distinct from that including the pandemic strain RIMD2210633, clinical isolates from other geographical regions, and
tdh
+
,
trh
-negative environmental isolates from the PNW. We detected T3SS2-related genes (T3SS2β) in environmental strains that were
tdh
and
trh
negative. The presence of significant concentrations of
tdh
+
,
trh
-negative environmental strains in the PNW that have not been responsible for illness and T3SS2β in
tdh
- and
trh
-negative strains emphasizes the diversity in this species and the need to identify additional virulence markers for this bacterium to improve risk assessment tools for the detection of this pathogen.
Evaluation of a Genome-Scale
In Silico
Metabolic Model for Geobacter metallireducens by Using Proteomic Data from a Field Biostimulation Experiment
Authors: Fang Yilin , Wilkins Michael J. , Yabusaki Steven B. , Lipton Mary S. , Long Philip E. 
Published: October 2012

ABSTRACT

Accurately predicting the interactions between microbial metabolism and the physical subsurface environment is necessary to enhance subsurface energy development, soil and groundwater cleanup, and carbon management. This study was an initial attempt to confirm the metabolic functional roles within an
in silico
model using environmental proteomic data collected during field experiments. Shotgun global proteomics data collected during a subsurface biostimulation experiment were used to validate a genome-scale metabolic model of
Geobacter metallireducens
—specifically, the ability of the metabolic model to predict metal reduction, biomass yield, and growth rate under dynamic field conditions. The constraint-based
in silico
model
of G. metallireducens
relates an annotated genome sequence to the physiological functions with 697 reactions controlled by 747 enzyme-coding genes. Proteomic analysis showed that 180 of the 637
G. metallireducens
proteins detected during the 2008 experiment were associated with specific metabolic reactions in the
in silico
model. When the field-calibrated Fe(III) terminal electron acceptor process reaction in a reactive transport model for the field experiments was replaced with the genome-scale model, the model predicted that the largest metabolic fluxes through the
in silico
model reactions generally correspond to the highest abundances of proteins that catalyze those reactions. Central metabolism predicted by the model agrees well with protein abundance profiles inferred from proteomic analysis. Model discrepancies with the proteomic data, such as the relatively low abundances of proteins associated with amino acid transport and metabolism, revealed pathways or flux constraints in the
in silico
model that could be updated to more accurately predict metabolic processes that occur in the subsurface environment.
Effect of the Bacillus atrophaeus subsp. globigii Spo0F H101R Mutation on Strain Fitness
Authors: Zhelev Doncho V. , Hunt Mia , Le Anna , Dupuis Christopher , Ren Suelynn , Gibbons Henry S. 
Published: October 2012

ABSTRACT

Sporulation is a critical developmental process in
Bacillus
spp. that, once initiated, removes the possibility of further growth until germination. Therefore, the threshold conditions triggering sporulation are likely to be subject to evolutionary constraint. Our previous studies revealed two spontaneous hypersporulating mutants of
Bacillus atrophaeus
subsp.
globigii
, both containing point mutations in the
spo0F
gene. One of these strains (Detrick-2; contains the
spo0F101
allele with a C:T [His101Arg] substitution) had been deliberately selected in the early 1940s as an anthrax surrogate. To determine whether the experimental conditions used during the selection of the “military” strains could have supported the emergence of hypersporulating variants, the relative fitness of strain Detrick-2 was measured in several experimental settings modeled on experimental conditions employed during its development in the 1940s as a simulant. The congenic strain Detrick-1 contained a wild-type
spo0F
gene and sporulated like the wild-type strain. The relative fitness of Detrick-1 and Detrick-2 was evaluated in competition experiments using quantitative single nucleotide polymorphism (SNP)-specific real-time PCR assays directed at the C:T substitution. The ancestral strain Detrick-1 had a fitness advantage under all conditions tested except when competing cultures were subjected to frequent heat shocks. The hypersporulating strain gained the maximum fitness advantage when cultures were grown at low oxygen tension and when heat shock was applied soon after the formation of the first heat-resistant spores. This is interpreted as gain of fitness by the hypersporulating strain in fast-changing fluctuating environments as a result of the increased rate of switching to the sporulating phenotype.
Rare Branched Fatty Acids Characterize the Lipid Composition of the Intra-Aerobic Methane Oxidizer “Candidatus Methylomirabilis oxyfera”
Authors: Kool Dorien M. , Zhu Baoli , Rijpstra W. Irene C. , Jetten Mike S. M. , Ettwig Katharina F. , Sinninghe Damsté Jaap S. 
Published: October 2012

ABSTRACT

The recently described bacterium “
Candidatus
Methylomirabilis oxyfera” couples the oxidation of the important greenhouse gas methane to the reduction of nitrite. The ecological significance of “
Ca
. Methylomirabilis oxyfera” is still underexplored, as our ability to identify the presence of this bacterium is thus far limited to DNA-based techniques. Here, we investigated the lipid composition of “
Ca
. Methylomirabilis oxyfera” to identify new, gene-independent biomarkers for the environmental detection of this bacterium. Multiple “
Ca
. Methylomirabilis oxyfera” enrichment cultures were investigated. In all cultures, the lipid profile was dominated up to 46% by the fatty acid (FA) 10-methylhexadecanoic acid (10MeC
16:0
). Furthermore, a unique FA was identified that has not been reported elsewhere: the monounsaturated 10-methylhexadecenoic acid with a double bond at the Δ7 position (10MeC
16:1Δ7
), which comprised up to 10% of the total FA profile. We propose that the typical branched fatty acids 10MeC
16:0
and 10MeC
16:1Δ7
are key and characteristic components of the lipid profile of “
Ca
. Methylomirabilis oxyfera.” The successful detection of these fatty acids in a peatland from which one of the enrichment cultures originated supports the potential of these unique lipids as biomarkers for the process of nitrite-dependent methane oxidation in the environment.
Anaerobic Oxidization of Methane in a Minerotrophic Peatland: Enrichment of Nitrite-Dependent Methane-Oxidizing Bacteria
Authors: Zhu Baoli , van Dijk Gijs , Fritz Christian , Smolders Alfons J. P. , Pol Arjan , Jetten Mike S. M. , Ettwig Katharina F. 
Published: October 2012

ABSTRACT

The importance of anaerobic oxidation of methane (AOM) as a methane sink in freshwater systems is largely unexplored, particularly in peat ecosystems. Nitrite-dependent anaerobic methane oxidation (n-damo) was recently discovered and reported to be catalyzed by the bacterium “
Candidatus
Methylomirabilis oxyfera,” which is affiliated with the NC10 phylum. So far, several “
Ca
. Methylomirabilis oxyfera” enrichment cultures have been obtained using a limited number of freshwater sediments or wastewater treatment sludge as the inoculum. In this study, using stable isotope measurements and porewater profiles, we investigated the potential of n-damo in a minerotrophic peatland in the south of the Netherlands that is infiltrated by nitrate-rich ground water. Methane and nitrate profiles suggested that all methane produced was oxidized before reaching the oxic layer, and NC10 bacteria could be active in the transition zone where countergradients of methane and nitrate occur. Quantitative PCR showed high NC10 bacterial cell numbers at this methane-nitrate transition zone. This soil section was used to enrich the prevalent NC10 bacteria in a continuous culture supplied with methane and nitrite at an
in situ
pH of 6.2. An enrichment of nitrite-reducing methanotrophic NC10 bacteria was successfully obtained. Phylogenetic analysis of retrieved 16S rRNA and
pmoA
genes showed that the enriched bacteria were very similar to the ones found
in situ
and constituted a new branch of NC10 bacteria with an identity of less than 96 and 90% to the 16S rRNA and
pmoA
genes of “
Ca
. Methylomirabilis oxyfera,” respectively. The results of this study expand our knowledge of the diversity and distribution of NC10 bacteria in the environment and highlight their potential contribution to nitrogen and methane cycles.
Fatty Acid Cosubstrates Provide β-Oxidation Precursors for Rhamnolipid Biosynthesis in Pseudomonas aeruginosa, as Evidenced by Isotope Tracing and Gene Expression Assays
Authors: Zhang Lin , Veres-Schalnat Tracey A. , Somogyi Arpad , Pemberton Jeanne E. , Maier Raina M. 
Published: October 2012

ABSTRACT

Rhamnolipids have multiple potential applications as “green” surfactants for industry, remediation, and medicine. As a result, they have been intensively investigated to add to our understanding of their biosynthesis and improve yields. Several studies have noted that the addition of a fatty acid cosubstrate increases rhamnolipid yields, but a metabolic explanation has not been offered, partly because biosynthesis studies to date have used sugar or sugar derivatives as the carbon source. The objective of this study was to investigate the role of fatty acid cosubstrates in improving rhamnolipid biosynthesis. A combination of stable isotope tracing and gene expression assays was used to identify lipid precursors and potential lipid metabolic pathways used in rhamnolipid synthesis when fatty acid cosubstrates are present. To this end, we compared the rhamnolipids produced and their yields using either glucose alone or glucose and octadecanoic acid-

d
35

as cosubstrates. Using a combination of sugar and fatty acids, the rhamnolipid yield was significantly higher (i.e., doubled) than when glucose was used alone. Two patterns of deuterium incorporation (either 1 or 15 deuterium atoms) in a single Rha-C
10
lipid chain were observed for octadecanoic acid-

d
35

treatment, indicating that in the presence of a fatty acid cosubstrate, both
de novo
fatty acid synthesis and β-oxidation are used to provide lipid precursors for rhamnolipids. Gene expression assays showed a 200- to 600-fold increase in the expression of
rhlA
and
rhlB
rhamnolipid biosynthesis genes and a more modest increase of 3- to 4-fold of the
fadA
β-oxidation pathway gene when octadecanoic acid was present. Taken together, these results suggest that the simultaneous use of
de novo
fatty acid synthesis and β-oxidation pathways allows for higher production of lipid precursors, resulting in increased rhamnolipid yields.