bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spectroscopic investigations of the molecular interaction of anticancer drug mitoxantrone with non-ionic surfactant micelles
Authors: Enache Mirela , Volanschi Elena 
Published: February 2012

Abstract

Objectives
The aim of this study was to investigate the interaction of the anticancer drug mitoxantrone with non-ionic micelles, as simple model systems of biological membranes.

Methods
UV-VIS absorption spectroscopy was used to quantify the drug–surfactant micelle interactions in terms of the binding constant and the micelle–water partition coefficient of the drug.

Key findings
Interaction of mitoxantrone with non-ionic micelles reduces the dimerization process of mitoxantrone, the drug molecules being encapsulated into micelles as monomer. The strength of the interaction between mitoxantrone and non-ionic micelles is higher at pH 10 than at pH 7.4, and depends on the surfactant in the order Tween 80 &gt; Tween 20 &gt; Triton X-100. The higher partition coefficient at pH 10 compared to pH 7.4 suggests that at basic pH the deprotonated mitoxantrone is incorporated more efficiently into the hydrophobic medium of non-ionic micelles compared to physiological pH, when the protonated drug is predominant.

Conclusions
These results on simple model systems miming the drug–membrane interactions contribute to the elucidation of the behaviour of the drug in vivo, as well as the possible utilization of surfactant micelles as drug carriers.
Serine-proteases as plasminogen activators in terms of fibrinolysis
Authors: Flemmig Martin , Melzig Matthias F 
Published: February 2012

Abstract

Objectives
This review should give an overview about the natural human plasminogen activators and their various modified variants as well as similar substances isolated from animals, microorganisms and plants. When a blood clot is formed in a blood vessel, it avoids the oxygen supply of the surrounding tissue. A fast fibrinolytic therapy should redissolve the blood vessel and reduce the degradation of the tissue. All proteases that are part of the human blood coagulation and fibrinolytic system belong to the serine protease family. t-PA (tissue plasminogen activator) and u-PA (urokinase plasminogen activator) are the naturally occurring fibrinolytic agents that are also used in therapy.

Key findings
Despite many years of research, t-PA is still the gold standard in fibrinolytic therapy. But it has to be given as an infusion, which needs time. Modified fibrinolytic substances are, were, or perhaps will be in the market. They have different advantages over t-PA, but often the disadvantages predominate.

Conclusion
Many substances have been developed but an optimal fibrinolytic agent combined with a simple administration is not in therapeutic use to date.
Advanced in vitro approach to study neurovascular coupling mechanisms in the brain microcirculation
Authors: Kim Ki Jung , Filosa Jessica A. 
Published: February 2012

Key points
We show that parenchymal arterioles of less than 30 μm in diameter can be successfully cannulated and perfused in cortical and hypothalamic brain slices.
Increased flow/pressure induced parenchymal arteriolar constriction.
Alternatively to video microscopy, diameter measurements of cannulated arterioles could be obtained from perfusion velocity values obtained using fluorescence recovery after photobleaching.
Perfused and pressurized parenchymal arterioles responded with dilatation to two well‐established signals in neurovascular coupling, K+ (10 mM) and activation of metabotropic glutamate receptors (mGluRs).
Synthetic localized calcium transients directly probe signalling mechanisms in skeletal muscle
Authors: Figueroa Lourdes , Shkryl Vyacheslav M. , Zhou Jingsong , Manno Carlo , Momotake Atsuya , Brum Gustavo , Blatter Lothar A. , Ellis‐Davies Graham C. R. , Ríos Eduardo 
Published: February 2012

Key points
The signal for skeletal muscle contraction is a rapid increase in cytosolic Ca2+ concentration, which requires the coordinated opening of ryanodine receptor (RyR) channels in the sarcoplasmic reticulum.
Channel opening is controlled by voltage‐sensing dihydropyridine receptors (DHPRs) of plasma membrane and T tubules. Whether or not their signal is amplified by Ca2+‐induced Ca2+ release (CICR) is controversial.
We used two‐photon lysis of an advanced Ca2+ cage to produce local Ca2+ concentration transients that were large, fast, reproducible and quantifiable, while monitoring the cellular response with a dual confocal laser scanner.
Single frog muscle cells in physiological solutions responded to transients greater than 0.28 μm with propagated CICR waves.
Mouse cells did not respond to stimuli up to 8 μm, unless channel opening drugs were present.
We conclude that CICR contributes to physiological Ca2+ release in frog but not mouse muscle.
Mice and presumably other mammals do have a capability for CICR that is normally inhibited. It could be manifested under special circumstances, including diseases.
The T788G Mutation in the
cyp51C
Gene Confers Voriconazole Resistance in Aspergillus flavus Causing Aspergillosis
Authors: Liu Wei , Sun Yi , Chen Wei , Liu Weixia , Wan Zhe , Bu Dingfang , Li Ruoyu 
Published: February 2012

ABSTRACT

With voriconazole (VRC) being approved as the first choice in treating invasive aspergillosis (IA) and its increasing use in treatment, a VRC-resistant strain of
Aspergillus flavus
, the second leading cause of IA after
Aspergillus fumigatus
, has emerged. The VRC-resistant strain of
A. flavus
was isolated for the first time from the surgical lung specimen of an IA patient with no response to VRC therapy. In order to ascertain the mechanism of VRC resistance, the azole target enzyme genes in this strain of
A. flavus
were cloned and sequenced, and 4 mutations generating amino acid residue substitutions were found in the
cyp51C
gene. To further determine the role of this mutated gene for VRC resistance in
A. flavus
, an
Agrobacterium tumefaciens
-mediated gene replacement approach was applied. Consequently, the mutated
cyp51C
gene from this
A. flavus
strain was proven to confer the VRC resistance. Finally, to discern the one out of the four mutations in the
cyp51C
gene that is responsible for contributing to VRC resistance, a site-directed gene mutagenesis procedure combined with a gene replacement method was performed. As a result, the T788G missense mutation in the
cyp51C
gene was identified as responsible for VRC resistance in
A. flavus
. These findings indicated that the detection of this mutation in
A. flavus
could serve as an indicator for physicians to avoid the use of VRC during IA treatment. Further comprehensive surveillance for antifungal susceptibility, as well as intensive study on the mechanism of azole resistance in
A. flavus
causing IA, would be required to fully understand this mechanism.
Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing
Authors: Jakobsen Tim Holm , van Gennip Maria , Phipps Richard Kerry , Shanmugham Meenakshi Sundaram , Christensen Louise Dahl , Alhede Morten , Skindersoe Mette Eline , Rasmussen Thomas Bovbjerg , Friedrich Karlheinz , Uthe Friedrich , Jensen Peter Østrup , Moser Claus , Nielsen Kristian Fog , Eberl Leo , Larsen Thomas Ostenfeld , Tanner David , Høiby Niels , Bjarnsholt Thomas , Givskov Michael 
Published: February 2012

ABSTRACTIn relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria likePseudomonas aeruginosato synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previousin vitroandin vivostudies revealed a significant inhibition ofP. aeruginosaQS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensivein vitroandin vivostudies, the effect of synthetic ajoene towardP. aeruginosawas elucidated. DNA microarray studies of ajoene-treatedP. aeruginosacultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment ofin vitrobiofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infectingP. aeruginosawas detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.
Integrating Conjugative Elements as Vectors of Antibiotic, Mercury, and Quaternary Ammonium Compound Resistance in Marine Aquaculture Environments
Authors: Rodríguez-Blanco Arturo , Lemos Manuel L. , Osorio Carlos R. 
Published: February 2012

ABSTRACT

The presence of SXT/R391-related integrating conjugative elements (ICEs) in bacterial strains isolated from fish obtained from marine aquaculture environments in 2001 to 2010 in the northwestern Iberian Peninsula was studied. ICEs were detected in 12 strains taxonomically related to
Vibrio scophthalmi
(3 strains),
Vibrio splendidus
(5 strains),
Vibrio alginolyticus
(1 strain),
Shewanella haliotis
(1 strain), and
Enterovibrio nigricans
(2 strains), broadening the known host range able to harbor SXT/R391-like ICEs. Variable DNA regions, which confer element-specific properties to ICEs of this family, were characterized. One of the ICEs encoded antibiotic resistance functions in variable region III, consisting of a tetracycline resistance locus. Interestingly, hot spot 4 included genes providing resistance to rifampin (ICE
Vsp
Por2 and ICE
Val
Por1) and quaternary ammonium compounds (QACs) (ICE
Eni
Spa1), and variable region IV included a mercury resistance operon (ICE
Vsp
Spa1 and ICE
Eni
Spa1). The S exclusion group was more represented than the R exclusion group, accounting for two-thirds of the total ICEs. Mating experiments allowed ICE mobilization to
Escherichia coli
strains, showing the corresponding transconjugants' rifampin, mercury, and QAC resistance. These results show the first evidence of ICEs providing rifampin and QAC resistances, suggesting that these mobile genetic elements contribute to the dissemination of antimicrobial, heavy metal, and QAC resistance determinants in aquaculture environments.
Expression, Immunogenicity, Histopathology, and Potency of a Mosquito-Based Malaria Transmission-Blocking Recombinant Vaccine
Authors: Mathias D. K. , Plieskatt J. L. , Armistead J. S. , Bethony J. M. , Abdul-Majid K. B. , McMillan A. , Angov E. , Aryee M. J. , Zhan B. , Gillespie P. , Keegan B. , Jariwala A. R. , Rezende W. , Bottazzi M. E. , Scorpio D. G. , Hotez P. J. , Dinglasan R. R. 
Published: February 2012

ABSTRACT

Vaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmission-blocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genus
Anopheles
, targeting mosquito midgut antigens that serve as ligands for
Plasmodium
parasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across
Anopheles
vectors and is a putative ligand for
Plasmodium
ookinete invasion. We have developed a scalable, high-yield
Escherichia coli
expression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization-associated histopathologies in a small-animal model.
Bundle-Forming Pilus Locus of Aeromonas veronii bv. Sobria
Authors: Hadi Nahal , Yang Qin , Barnett Timothy C. , Tabei S. Mohammed B. , Kirov Sylvia M. , Shaw Jonathan G. 
Published: February 2012

ABSTRACT

Little is known about the colonization mechanisms of
Aeromonas
spp. Previous work has suggested that the type IV bundle-forming pilus (Bfp) is an aeromonad intestinal colonization factor. This study provides the first genetic characterization of this structure. To define the role of Bfp in
Aeromonas veronii
bv. Sobria adherence, a 22-kb locus encoding the bundle-forming pilus was isolated; this contained 17 pilus-related genes similar to the mannose-sensitive hemagglutinin (MSHA) of
Vibrio cholerae
. Reverse transcriptase PCR (RT-PCR) demonstrated that the locus had two major transcriptional units,
mshI
to
mshF
and
mshB
to
mshQ
. Transcriptional fusion experiments demonstrated the presence of two strong promoters upstream of
mshI
and
mshB
. The locus encoded four putative prepilin proteins, one of which (MshA) corresponded to the N-terminal sequence of the previously isolated major pilin protein. All the pilin genes were inactivated, mutation of each minor or major pilin gene greatly reduced the bacterium's ability to adhere and form biofilms, and complementation of each mutant in
trans
rescued this phenotype. Mutation of the major pilin MshA and MshB, a minor pilin, resulted in their loss. The position of the
mshH
gene is conserved within a number of bacteria, and we have shown it is not transcriptionally linked to the other
msh
genes; moreover, its mutation did not have a dramatic effect on either adhesion or biofilm formation. We conclude that the bundle-forming pilus is required for
A. veronii
bv. Sobria adherence and biofilm formation; furthermore, both the major and minor pilin proteins are essential for this process.
Strain-Specific Regulatory Role of Eukaryote-Like Serine/Threonine Phosphatase in Pneumococcal Adherence
Authors: Agarwal Shivangi , Agarwal Shivani , Pancholi Preeti , Pancholi Vijay 
Published: February 2012

ABSTRACT

Streptococcus pneumoniae
exploits a battery of virulence factors to colonize the host. Although the eukaryote-like Ser/Thr kinase of
S. pneumoniae
(StkP) has been implicated in physiology and virulence, the role of its cotranscribing phosphatase (PhpP) has remained elusive. The construction of nonpolar markerless
phpP
knockout mutants (Δ
phpP
) in two pathogenic strains, D39 (type 2) and 6A-EF3114 (type 6A), indicated that PhpP is not indispensable for pneumococcal survival. Further, PhpP also participates in the regulation of cell wall biosynthesis/division, adherence, and biofilm formation in a strain-specific manner. Additionally, we provide hitherto-unknown
in vitro
and
in vivo
evidence of a physiologically relevant biochemical link between the StkP/PhpP-mediated cognate regulation and the two-component regulatory system TCS06 (RR06/HK06) that regulates the expression of the gene encoding an important pneumococcal surface adhesin, CbpA, which was found to be significantly upregulated in Δ
phpP
mutants. In particular, StkP (threonine)-phosphorylated RR06 bound to the
cbpA
promoter with high efficiency even in the absence of the HK06-responsive and catalytically active aspartate 51 residue. Together, our findings unravel the significant contributions of PhpP in pneumococcal physiology and adherence.
DksA-Dependent Resistance of Salmonella enterica Serovar Typhimurium against the Antimicrobial Activity of Inducible Nitric Oxide Synthase
Authors: Henard Calvin A. , Vázquez-Torres Andrés 
Published: February 2012

ABSTRACT

In coordination with the ppGpp alarmone, the RNA polymerase regulatory protein DksA controls the stringent response of eubacteria, negatively regulating transcription of translational machinery and directly activating amino acid promoters and
de novo
amino acid biosynthesis. Given the effects of nitric oxide (NO) on amino acid biosynthetic pathways and the intimate relationship of DksA with amino acid synthesis and transport, we tested whether DksA contributes to the resistance of
Salmonella
to reactive nitrogen species (RNS). Our studies show that the zinc finger predicted to position DksA in the secondary channel of the RNA polymerase is essential for the resistance of
Salmonella enterica
serovar Typhimurium to RNS in a murine model of systemic salmonellosis. Despite exhibiting auxotrophies for various amino acids, Δ
dksA
mutant
Salmonella
strains regain virulence in mice lacking inducible NO synthase (iNOS). DksA is also important for growth of this intracellular pathogen in the presence of NO congeners generated by iNOS during the innate response of murine macrophages. Accordingly,
dksA
mutant
Salmonella
strains are hypersusceptible to chemically generated NO, a phenotype that can be prevented by adding amino acids. The DksA-dependent antinitrosative defenses do not rely on the Hmp flavohemoprotein that detoxifies NO to NO
3
−
and appear to operate independently of the ppGpp alarmone. Our investigations are consistent with a model by which NO produced in the innate response to
Salmonella
exerts considerable pressure on amino acid biosynthesis. The cytotoxicity of NO against
Salmonella
amino acid biosynthetic pathways is antagonized in great part by the DksA-dependent regulation of amino acid biosynthesis and transport.
Accuracy of ECG interpretation in competitive athletes: the impact of using standardised ECG criteria
Authors: Drezner Jonathan A , Asif Irfan M , Owens David S , Prutkin Jordan M , Salerno Jack C , Fean Robyn , Rao Ashwin L , Stout Karen , Harmon Kimberly G 
Published: February 2012

BackgroundInterpretation of ECGs in athletes is complicated by physiological changes related to training. The purpose of this study was to determine the accuracy of ECG interpretation in athletes among different physician specialties, with and without use of a standised ECG criteria tool.MethodsPhysicians were asked to interpret 40 ECGs (28 normal ECGs from college athletes randomised with 12 abnormal ECGs from individuals with known ciovascular pathology) and classify each ECG as (1) ‘normal or variant – no further evaluation and testing needed’ or (2) ‘abnormal – further evaluation and testing needed.’ After reading the ECGs, participants received a two-page ECG criteria tool to guide interpretation of the ECGs again.ResultsA total of 60 physicians participated: 22 primary care (PC) residents, 16 PC attending physicians, 12 sports medicine (SM) physicians and 10 ciologists. At baseline, the total number of ECGs correctly interpreted was PC residents 73%, PC attendings 73%, SM physicians 78% and ciologists 85%. With use of the ECG criteria tool, all physician groups significantly improved their accuracy (p<0.0001): PC residents 92%, PC attendings 90%, SM physicians 91% and ciologists 96%. With use of the ECG criteria tool, specificity improved from 70% to 91%, sensitivity improved from 89% to 94% and there was no difference comparing ciologists versus all other physicians (p=0.053).ConclusionsProviding standised criteria to assist ECG interpretation in athletes significantly improves the ability to accurately distinguish normal from abnormal findings across physician specialties, even in physicians with little or no experience.
Childhood residential mobility and health in late adolescence and adulthood: findings from the West of Scotland Twenty-07 Study
Authors: Brown D , Benzeval M , Gayle V , Macintyre S , O'Reilly D , Leyland A H 
Published: February 2012

BackgroundThe relationship between childhood residential mobility and health in the UK is not well established; however, research elsewhere suggests that frequent childhood moves may be associated with poorer health outcomes and behaviours. The aim of this paper was to compare people in the West of Scotland who were residentially stable in childhood with those who had moved in terms of a range of health measures.MethodsA total of 850 respondents, followed-up for a period of 20 years, were included in this analysis. Childhood residential mobility was derived from the number of addresses lived at between birth and age 18. Multilevel regression was used to investigate the relationship between childhood residential mobility and health in late adolescence (age 18) and adulthood (age 36), accounting for socio-demographic characteristics and frequency of school moves. The authors examined physical health measures, overall health, psychological distress and health behaviours.ResultsTwenty per cent of respondents remained stable during childhood, 59% moved one to two times and 21% moved at least three times. For most health measures (except physical health), there was an increased risk of poor health that remained elevated for frequent movers after adjustment for socio-demographic characteristics and school moves (but was only significant for illegal drug use).ConclusionsRisk of poor health was elevated in adolescence and adulthood with increased residential mobility in childhood, after adjusting for socio-demographic characteristics and school moves. This was true for overall health, psychological distress and health behaviours, but physical health measures were not associated with childhood mobility.
Pebbles and Branching Programs for Tree Evaluation
Authors: Cook Stephen , McKenzie Pierre , Wehr Dustin , Braverman Mark , Santhanam Rahul 
Published: February 2012

We introduce the
tree evaluation problem
, show that it is in
LogDCFL
(and hence in
P
), and study its branching program complexity in the hope of eventually proving a superlogarithmic space lower bound. The input to the problem is a rooted, balanced
d
-ary tree of height
h
, whose internal nodes are labeled with
d
-ary functions on [
k
] = {1,...,
k
}, and whose leaves are labeled with elements of [
k
]. Each node obtains a value in [
k
] equal to its
d
-ary function applied to the values of its
d
children. The output is the value of the root. We show that the standard black pebbling algorithm applied to the binary tree of height
h
yields a deterministic
k
-way branching program with
O
(
k
h
) states solving this problem, and we prove that this upper bound is tight for
h
= 2 and
h
= 3. We introduce a simple semantic restriction called
thrifty
on
k
-way branching programs solving tree evaluation problems and show that the same state bound of
Θ
(
k
h
) is tight for all
h
≥ 2 for deterministic thrifty programs. We introduce fractional pebbling for trees and show that this yields nondeterministic thrifty programs with
Θ
(
k
h/2+1
) states solving the Boolean problem “determine whether the root has value 1”, and prove that this bound is tight for
h
= 2,3,4. We also prove that this same bound is tight for unrestricted nondeterministic
k
-way branching programs solving the Boolean problem for
h
= 2,3.