bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supersaturated dissolution data and their interpretation: the TPGS–carbamazepine model case
Authors: Charkoftaki Georgia , Dokoumetzidis Aristides , Valsami Georgia , Macheras Panos 
Published: February 2011

Abstract

Objectives
This study was undertaken to investigate the effect of d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) on the dissolution of carbamazepine (CBZ) commercial tablets (Tegretol®) as a function of temperature and to modify the reaction-limited model of dissolution for the description of classical supersaturated dissolution data.

Methods
Solubility studies were performed using various concentrations of (i) TPGS and (ii) silicon dioxide and microcrystalline cellulose, which are excipients of Tegretol® at 10, 25 and 37°C. Dissolution studies were carried out using Tegretol® tablets, 200 mg/tab.

Key findings
The solubility of CBZ in the presence of TPGS was found to increase in a concentration-dependent manner at all temperatures studied. Classical supersaturated dissolution curves with concentration maxima higher than the corresponding solubility values in the presence of TPGS were observed only at 10°C. The model developed was based on a time-dependant expression for the forward microconstant of the CBZ-TPGS reaction at the solid–liquid interface and it was fitted successfully to the dissolution data of CBZ in the presence of TPGS at 10°C.

Conclusions
Vitamin E TPGS increased the solubility of CBZ at all temperatures studied. The modification of the reaction-limited model of dissolution allowed us to describe classical supersaturated dissolution curves.
Inhalable, bioresponsive microparticles for targeted drug delivery in the lungs
Authors: Sivadas Neeraj , Cryan Sally-Ann 
Published: February 2011

Abstract

Objective
There is a growing interest in developing bioresponsive drug delivery systems to achieve greater control over drug release than can be achieved with the conventional diffusion controlled polymeric delivery systems. While a number of such systems have been studied for oral or parenteral delivery, little or no work has been done on bioresponsive delivery systems for inhalation. Using the raised elastase levels present at sites of lung inflammation as a proof-of-concept model, we endeavoured to develop a prototype of inhalable elastase sensitive microparticles (ESMs).

Methods
Microparticles degradable by the enzyme elastase were formed by crosslinking the polymer alginate in the presence of an elastase substrate, elastin, using Ca+2 ions and subsequent spray drying.

Key findings
The bioresponsive release of a protein cargo in the presence of elastase demonstrated the enzyme-specific degradability of the particles. The microparticles showed favorable properties such as high drug encapsulation and good powder dispersibility. Potential polymer toxicity in the lungs was assessed by impinging the microparticles on Calu-3 cell monolayers and assessing changes in transepithelial permeability and induction of cytokine release. The microparticles displayed no toxic or immunogenic effects.

Conclusions
With a manufacturing method that is amenable to scale-up, the ability to be aerosolised efficiently from a first-generation inhaler device, enzyme-specific degradability and lack of toxicity, the ESMs show significant promise as pulmonary drug carriers.
Demographic risk factors affecting emergency room visits caused by benzodiazepine poisoning in Kansas City, Missouri, from 2001 to 2007
Authors: Liu Yifei , Cai Jinwen , Hoff Gerald L , Hong Liang , Okah Felix A 
Published: February 2011

Abstract

Objective
The study objective was to identify demographic risk factors associated with emergency room visits caused by benzodiazepine poisoning.

Methods
A retrospective study was conducted utilizing Missouri Hospital Discharge Data for Kansas City, Missouri, USA, for 2001–2007. The data included patients' demographics such as racial group, age, sex, health insurance status and annual income. Emergency room visits due to benzodiazepine poisoning were identified by ICD-9 code 969.4. The frequencies of patient visits were calculated according to categories of each demographic variable. Chi-square tests were used to assess the difference of emergency room visits among categories of each demographic variable. A multiple logistic regression analysis was performed, where the outcome variable was emergency room visits due to benzodiazepine poisoning (yes/no), and the independent variables were the demographic variables.

Key findings
Of 1 317 566 emergency room visits over the 7-year period, 562 were due to benzodiazepine poisoning. Seventy-seven per cent of these visits were made by patients who were white, of whom 53% were 30–49 years old, 56% were female, 74% had health insurance and 44% lived in zip codes with median family incomes of $40 000–59 999. Chi-square tests were significant for racial group, age and annual income (P &lt; 0.01). In the logistic regression white patients were 73% more likely than black patients to have emergency room visits caused by benzodiazepine poisoning (P &lt; 0.01), with an odds ratio (95% confidence interval) of 5.63 (4.33–7.30). Compared with those aged 0–19 years, the odds ratio for patients aged 30–39 to have such visits was 2.73 (2.09–3.57), and the odds ratio for patients aged 40–49 was 2.84 (2.17–3.71).

Conclusions
White patients and patients aged 30–49 years were at higher risk for emergency room visits due to benzodiazepine poisoning. Health interventions such as medication review by pharmacists may reduce the risk of benzodiazepine poisoning for these patients.
Childhood trauma in obsessive compulsive disorder: The roles of alexithymia and attachment
Authors: Carpenter Leanne , Chung Man Cheung 
Published: February 2011

Objective. The aim of this study was to investigate the interrelationships between childhood trauma, attachment, alexithymia, and the severity of obsessive compulsive disorder (OCD) in a cohort of participants with OCD.Rationale. There is a growing body of research linking traumatic experiences in childhood with the development of OCD. The mechanisms involved in this association are not yet clear.Methods. The sample was comprised of 82 people with OCD and 92 comparison participants. A cross‐sectional design was used, utilizing internet‐mediated administration of the Childhood Trauma Questionnaire – revised (CTQ‐R); the Yale‐Brown Obsessive Compulsive Scale – Self‐Report (Y‐BOCS‐SR); the Experiences in Close Relationships Scale (ECR); and Toronto Alexithymia Scale (TAS‐20). Partial least squares (PLS) analysis was used to determine significant paths between the constructs.Results. Results of PLS analysis supported all of the hypotheses made: there was a significant positive correlation between childhood trauma and attachment avoidance, which in turn was significantly positively associated with alexithymia. Alexithymia was significantly associated with the severity of OCD symptoms and the number of OCD symptoms. Mediational analysis showed that alexithymia significantly carried an influence from attachment avoidance to the severity of obsessions and the number of obsession symptoms.Conclusions. There is a relationship between childhood trauma and OCD, however this relationship is not direct in nature but is influenced by peoples’ past experiences with significant others and associated difficulties in emotional processing.
Isolation of Highly Heat-Resistant Listeria monocytogenes Variants by Use of a Kinetic Modeling-Based Sampling Scheme
Authors: Van Boeijen Ineke K. H. , Francke Christof , Moezelaar Roy , Abee Tjakko , Zwietering Marcel H. 
Published: February 2011

ABSTRACT

Stable high-hydrostatic-pressure (HHP)-resistant
Listeria monocytogenes
LO28 variants were previously isolated and characterized. These HHP variants were also more resistant to heat. In addition, nonlinear heat inactivation kinetics pointed toward the existence of heat-resistant variants, although these could not be isolated so far. In this study, we used kinetic modeling of inactivation curves of two isolated HHP variants and their wild type, and this revealed that the probability of finding resistant variants should depend on the nature of the inactivation treatment and the time of exposure. At specific heat and HHP conditions, resistant LO28 and EGDe variants were indeed isolated. Resistant LO28 variants were even isolated after a heat inactivation at 72°C in milk, and these variants showed high resistance to standard pasteurization conditions. The increased resistance of part of the isolated LO28 and EGDe variants was due to mutations in their
ctsR
genes. For the variants whose
ctsR
genes and upstream regions were not altered, the mechanisms leading to increased resistance remain to be elucidated. This research showed the strength of kinetic modeling in unraveling the causes of nonlinear inactivation and facilitating the isolation of heat-resistant
L. monocytogenes
variants.
Moonlighting Role of a Poly-γ-Glutamate Synthetase Component from Bacillus subtilis: Insight into Novel Extrachromosomal DNA Maintenance
Authors: Yamashiro Daisuke , Minouchi Yutaka , Ashiuchi Makoto 
Published: February 2011

ABSTRACT

The
Bacillus subtilis
structural gene
pgsE
was investigated as a tool for extrachromosomal DNA maintenance (EDM). It ameliorated the stability of high-copy-number vectors, regardless of whether they were derived from rolling-cycle or theta-mode replicons, without any selective pressure. This unique EDM phenomenon may occur via a
trans
-acting mechanism.
Comparative Analysis of Antimicrobial Activities of Valinomycin and Cereulide, the Bacillus cereus Emetic Toxin
Authors: Tempelaars Marcel H. , Rodrigues Susana , Abee Tjakko 
Published: February 2011

ABSTRACT

Cereulide and valinomycin are highly similar cyclic dodecadepsipeptides with potassium ionophoric properties. Cereulide, produced by members of the
Bacillus cereus
group, is known mostly as emetic toxin, and no ecological function has been assigned. A comparative analysis of the antimicrobial activity of valinomycin produced by
Streptomyces
spp. and cereulide was performed at a pH range of pH 5.5 to pH 9.5, under anaerobic and aerobic conditions. Both compounds display pH-dependent activity against selected Gram-positive bacteria, including
Staphylococcus aureus
,
Listeria innocua
,
Listeria monocytogenes
,
Bacillus subtilis
, and
Bacillus cereus
ATCC 10987. Notably,
B. cereus
strain ATCC 14579 and the emetic
B. cereus
strains F4810/72 and A529 showed reduced sensitivity to both compounds, with the latter two strains displaying full resistance to cereulide. Both compounds showed no activity against the selected Gram-negative bacteria. Antimicrobial activity against Gram-positive bacteria was highest at alkaline pH values, where the membrane potential (ΔΨ) is the main component of the proton motive force (PMF). Furthermore, inhibition of growth was observed in both aerobic and anaerobic conditions. Determination of the ΔΨ, using the membrane potential probe DiOC
2
(3) (in the presence of 50 mM KCl) in combination with flow cytometry, demonstrated for the first time the ability of cereulide to dissipate the ΔΨ in sensitive Gram-positive bacteria. The putative role of cereulide production in the ecology of emetic
B. cereus
is discussed.
Detecting Potentially Virulent Vibrio vulnificus Strains in Raw Oysters by Quantitative Loop-Mediated Isothermal Amplification
Authors: Han Feifei , Wang Fei , Ge Beilei 
Published: February 2011

ABSTRACT

Vibrio vulnificus
is a leading cause of seafood-related deaths in the United States. Sequence variations in the virulence-correlated gene (
vcg
) have been used to distinguish between clinical and environmental
V. vulnificus
strains, with a strong association between clinical ones and the C sequence variant (
vcgC
). In this study,
vcgC
was selected as the target to design a loop-mediated isothermal amplification (LAMP) assay for the rapid, sensitive, specific, and quantitative detection of potentially virulent
V. vulnificus
strains in raw oysters. No false-positive or false-negative results were generated among the 125 bacterial strains used to evaluate assay specificity. The detection limit was 5.4 CFU per reaction for a virulent
V. vulnificus
strain (ATCC 33815) in pure culture, 100-fold more sensitive than that of PCR. In spiked raw oysters, the assay was capable of detecting 2.5 × 10
3
CFU/g of
V. vulnificus
ATCC 33815, while showing negative results for a nonvirulent
V. vulnificus
strain (515-4c2) spiked at 10
7
CFU/g. After 6 h of enrichment, the LAMP assay could detect 1 CFU/g of the virulent
V. vulnificus
strain ATCC 33815. Standard curves generated in pure culture and spiked oysters suggested a good linear relationship between cell numbers of the virulent
V. vulnificus
strain and turbidity signals. In conclusion, the LAMP assay developed in this study could quantitatively detect potentially virulent
V. vulnificus
in raw oysters with high speed, specificity, and sensitivity, which may facilitate better control of
V. vulnificus
risks associated with raw oyster consumption.
Mid1, a Mechanosensitive Calcium Ion Channel, Affects Growth, Development, and Ascospore Discharge in the Filamentous Fungus Gibberella zeae
Authors: Cavinder Brad , Hamam Ahmed , Lew Roger R. , Trail Frances 
Published: February 2011

ABSTRACTThe role of Mid1, a stretch-activated ion channel capable of being permeated by calcium, in ascospore development and forcible discharge from asci was examined in the pathogenic fungusGibberella zeae(anamorphFusarium graminearum). The Δmid1mutants exhibited a >12-fold reduction in ascospore discharge activity and produced predominately abnormal two-celled ascospores with constricted and fragile septae. The vegetative growth rate of the mutants was ∼50% of the wild-type rate, and production of macroconidia was >10-fold lower than in the wild type. To better understand the role of calcium flux, Δmid1Δcch1double mutants were also examined, as Cch1, an L-type calcium ion channel, is associated with Mid1 inSaccharomyces cerevisiae. The phenotype of the Δmid1Δcch1double mutants was similar to but more severe than the phenotype of the Δmid1mutants for all categories. Potential and current-voltage measurements were taken in the vegetative hyphae of the Δmid1and Δcch1mutants and the wild type, and the measurements for all three strains were remarkably similar, indicating that neither protein contributes significantly to the overall electrical properties of the plasma membrane. Pathogenicity of the Δmid1and Δmid1Δcch1mutants on the host (wheat) was not affected by the mutations. Exogenous calcium supplementation partially restored the ascospore discharge and vegetative growth defects for all mutants, but abnormal ascospores were still produced. These results extend the known roles of Mid1 to ascospore development and forcible discharge. However,Neurospora crassaΔmid1mutants were also examined and did not exhibit defects in ascospore development or in ascospore discharge. In comparison to ion channels in other ascomycetes, Mid1 shows remarkable adaptability of roles, particularly with regard to niche-specific adaptation.
Role of B Regulatory Subunits of Protein Phosphatase Type 2A in Myosin II Assembly Control in Dictyostelium discoideum
Authors: Rai Vandana , Egelhoff Thomas T. 
Published: February 2011

ABSTRACT

In
Dictyostelium discoideum
, myosin II resides predominantly in a soluble pool as the result of phosphorylation of the myosin heavy chain (MHC), and dephosphorylation of the MHC is required for myosin II filament assembly, recruitment to the cytoskeleton, and force production. Protein phosphatase type 2A (PP2A) was identified in earlier studies in
Dictyostelium
as a key biochemical activity that can drive MHC dephosphorylation. We report here gene targeting and cell biological studies addressing the roles of candidate PP2A B regulatory subunits (phr2aBα and phr2aBβ) in myosin II assembly control
in vivo
.
Dictyostelium
phr2aBα- and phr2aBβ-null cells show delayed development, reduction in the assembly of myosin II in cytoskeletal ghost assays, and defects in cytokinesis when grown in suspension compared to parental cell lines. These results demonstrate that the PP2A B subunits phr2aBα and phr2aBβ contribute to myosin II assembly control
in vivo
, with phr2aBα having the predominant role facilitating MHC dephosphorylation to facilitate filament assembly.
Conjugated Linoleic Acid Inhibits Hyphal Growth in Candida albicans by Modulating Ras1p Cellular Levels and Downregulating TEC1 Expression
Authors: Shareck Julie , Nantel André , Belhumeur Pierre 
Published: February 2011

ABSTRACT

The polymorphic yeast
Candida albicans
exists in yeast and filamentous forms. Given that the morphogenetic switch coincides with the expression of many virulence factors, the yeast-to-hypha transition constitutes an attractive target for the development of new antifungal agents. Since an untapped therapeutic potential resides in small molecules that hinder
C. albicans
filamentation, we characterized the inhibitory effect of conjugated linoleic acid (CLA) on hyphal growth and addressed its mechanism of action. CLA inhibited hyphal growth in a dose-dependent fashion in both liquid and solid hypha-inducing media. The fatty acid blocked germ tube formation without affecting cellular growth rates. Global transcriptional profiling revealed that CLA downregulated the expression of hypha-specific genes and abrogated the induction of several regulators of hyphal growth, including
TEC1
,
UME6
,
RFG1
, and
RAS1
. However, neither
UME6
nor
RFG1
was necessary for CLA-mediated hyphal growth inhibition. Expression analysis showed that the downregulation of
TEC1
expression levels by CLA depended on
RAS1
. In addition, while
RAS1
transcript levels remained constant in CLA-treated cells, its protein levels declined with time. With the use of a strain expressing GFP-Ras1p, CLA treatment was also shown to affect Ras1p localization to the plasma membrane. These findings suggest that CLA inhibits hyphal growth by affecting the cellular localization of Ras1p and blocking the increase in
RAS1
mRNA and protein levels. Combined, these effects should prevent the induction of the Ras1p signaling pathway. This study provides the biological and molecular explanations that underlie CLA's ability to inhibit hyphal growth in
C. albicans
.
Molecular Cloning and Characterization of the
srdBCA
Operon, Encoding the Respiratory Selenate Reductase Complex, from the Selenate-Reducing Bacterium Bacillus selenatarsenatis SF-1
Authors: Kuroda Masashi , Yamashita Mitsuo , Miwa Emiko , Imao Kanako , Fujimoto Noriyuki , Ono Hisayo , Nagano Kouta , Sei Kazunari , Ike Michihiko 
Published: February 2011

ABSTRACT

Previously, we isolated a selenate- and arsenate-reducing bacterium, designated strain SF-1, from selenium-contaminated sediment and identified it as a novel species,
Bacillus selenatarsenatis. B. selenatarsenatis
strain SF-1 independently reduces selenate to selenite, arsenate to arsenite, and nitrate to nitrite by anaerobic respiration. To identify the genes involved in selenate reduction, 17 selenate reduction-defective mutant strains were isolated from a mutant library generated by random insertion of transposon Tn
916
. Tn
916
was inserted into the same genome position in eight mutants, and the representative strain SF-1AM4 did not reduce selenate but did reduce nitrate and arsenate to the same extent as the wild-type strain. The disrupted gene was located in an operon composed of three genes designated
srdBCA
, which were predicted to encode a putative oxidoreductase complex by the BLASTX program. The plasmid vector pGEMsrdBCA, containing the
srdBCA
operon with its own promoter, conferred the phenotype of selenate reduction in
Escherichia coli
DH5α, although
E. coli
strains containing plasmids lacking any one or two of the open reading frames from
srdBCA
did not exhibit the selenate-reducing phenotype. Domain structure analysis of the deduced amino acid sequence revealed that SrdBCA had typical features of membrane-bound and molybdopterin-containing oxidoreductases. It was therefore proposed that the
srdBCA
operon encoded a respiratory selenate reductase complex. This is the first report of genes encoding selenate reductase in Gram-positive bacteria.
Mutation of a Broadly Conserved Operon (RL3499-RL3502) from Rhizobium leguminosarum Biovar
viciae
Causes Defects in Cell Morphology and Envelope Integrity
Authors: Vanderlinde Elizabeth M. , Magnus Samantha A. , Tambalo Dinah D. , Koval Susan F. , Yost Christopher K. 
Published: February 2011

ABSTRACT

The bacterial cell envelope is of critical importance to the function and survival of the cell; it acts as a barrier against harmful toxins while allowing the flow of nutrients into the cell. It also serves as a point of physical contact between a bacterial cell and its host. Hence, the cell envelope of
Rhizobium leguminosarum
is critical to cell survival under both free-living and symbiotic conditions. Transposon mutagenesis of
R. leguminosarum
strain 3841 followed by a screen to isolate mutants with defective cell envelopes led to the identification of a novel conserved operon (RL3499-RL3502) consisting of a putative
moxR
-like AAA
+
ATPase, a hypothetical protein with a domain of unknown function (designated domain of unknown function 58), and two hypothetical transmembrane proteins. Mutation of genes within this operon resulted in increased sensitivity to membrane-disruptive agents such as detergents, hydrophobic antibiotics, and alkaline pH. On minimal media, the mutants retain their rod shape but are roughly 3 times larger than the wild type. On media containing glycine or peptides such as yeast extract, the mutants form large, distorted spheres and are incapable of sustained growth under these culture conditions. Expression of the operon is maximal during the stationary phase of growth and is reduced in a
chvG
mutant, indicating a role for this sensor kinase in regulation of the operon. Our findings provide the first functional insight into these genes of unknown function, suggesting a possible role in cell envelope development in
Rhizobium leguminosarum
. Given the broad conservation of these genes among the
Alphaproteobacteria
, the results of this study may also provide insight into the physiological role of these genes in other
Alphaproteobacteria
, including the animal pathogen
Brucella
.
Single-Gene Deletion Mutants of Escherichia coli with Altered Sensitivity to Bicyclomycin, an Inhibitor of Transcription Termination Factor Rho
Authors: Tran Lillian , van Baarsel Joshua A. , Washburn Robert S. , Gottesman Max E. , Miller Jeffrey H. 
Published: February 2011

ABSTRACT

We have screened the entire KEIO collection of 3,985 single-gene knockouts in
Escherichia coli
for increased susceptibility or resistance to the antibiotic bicyclomycin (BCM), a potent inhibitor of the transcription termination factor Rho. We also compared the results to those of a recent study we conducted with a large set of antibiotics (A. Liu et al., Antimicrob. Agents Chemother.
54:
1393-1403, 2010). We find that deletions of many different types of genes increase sensitivity to BCM. Some of these are involved in multidrug sensitivity/resistance, whereas others are specific for BCM. Mutations in a number of DNA recombination and repair genes increase BCM sensitivity, indicating that DNA damage leading to single- and double-strand breaks is a downstream effect of Rho inhibition. MDS42, which is deleted for all cryptic prophages and insertion elements (G. Posfai et al., Science
312:
1044-1046, 2006), or W3102 deleted for the
rac
prophage-encoded
kil
gene, are partially resistant to BCM (C. J. Cardinale et al., Science
230:
935-938, 2008). Deletion of cryptic prophages also overcomes the increased BCM sensitivity in some but not all mutants examined here. Deletion of the
hns
gene renders the cell more sensitive to BCM even in the Δ
kil
or MDS42 background. This suggests that BCM activates additional modes of cell death independent of Kil and that these could provide a target to potentiate BCM killing.