bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient Clearance of
Aspergillus fumigatus
in Murine Lungs by an Ultrashort Antimicrobial Lipopeptide, Palmitoyl-Lys-Ala-
d
Ala-Lys
Authors: Vallon-Eberhard Alexandra , Makovitzki Arik , Beauvais Anne , Latgé Jean-Paul , Jung Steffen , Shai Yechiel 
Published: July 2008

ABSTRACT

Aspergillus fumigatus
is an opportunistic fungal pathogen responsible for invasive aspergillosis in immunocompromised individuals. The inefficiency of antifungal agents and high mortality rate resulting from invasive aspergillosis remain major clinical concerns. Recently, we reported on a new family of ultrashort cationic lipopeptides active in vitro against fungi. Mode of action studies supported a membranolytic or a detergent-like effect. Here, we screened several lipopeptides in vitro for their anti-
A. fumigatus
activity. To investigate the therapeutic properties of the selected peptides in vivo, we challenged immunosuppressed C57BL/6 wild-type mice intranasally with DsRed-labeled
A. fumigatus
conidia and subsequently treated the animals locally with the lipopeptides. Confocal microscopic analysis revealed the degradation of DsRed-labeled hyphal forms and residual conidia in the lungs of the mice. The most efficient peptide was tested further using a survival assay and was found to significantly prolong the life of the treated animals, whereas no mice survived with the current standard antifungal treatment with amphotericin B. Moreover, as opposed to the drug-treated lungs, the peptide-treated lungs did not display any toxicity of the peptide. Our results highlight the potential of this family of lipopeptides for the treatment of pulmonary invasive aspergillosis.
Identification and Biochemical Characterization of Small-Molecule Inhibitors of West Nile Virus Serine Protease by a High-Throughput Screen
Authors: Mueller Niklaus H. , Pattabiraman Nagarajan , Ansarah-Sobrinho Camilo , Viswanathan Prasanth , Pierson Theodore C. , Padmanabhan R. 
Published: July 2008

ABSTRACT

West Nile virus and dengue virus are mosquito-borne flaviviruses that cause a large number of human infections each year. No vaccines or chemotherapeutics are currently available. These viruses encode a serine protease that is essential for polyprotein processing, a required step in the viral replication cycle. In this study, a high-throughput screening assay for the West Nile virus protease was employed to screen ∼32,000 small-molecule compounds for identification of inhibitors. Lead inhibitor compounds with three distinct core chemical structures (1 to 3) were identified. In a secondary screening of selected compounds, two compounds, belonging to the 8-hydroxyquinoline family (compounds A and B) and containing core structure 1, were identified as potent inhibitors of the West Nile virus protease, with
K

i

values of 3.2 ± 0.3 μM and 3.4 ± 0.6 μM, respectively. These compounds inhibited the dengue virus type 2 protease with
K

i

values of 28.6 ± 5.1 μM and 30.2 ± 8.6 μM, respectively, showing some selectivity in the inhibition of these viral proteases. However, the compounds show no inhibition of cellular serine proteases, trypsin, or factor Xa. Kinetic analysis and molecular docking of compound B onto the known crystal structure of the West Nile virus protease indicate that the inhibitor binds in the substrate-binding cleft. Furthermore, compound B was capable of inhibiting West Nile virus RNA replication in cultured Vero cells (50% effective concentration, 1.4 ± 0.4 μM; selectivity index, 100), presumably by inhibition of polyprotein processing.
PCR Detection of Type I Polyketide Synthase Genes in Myxobacteria
Authors: Komaki Hisayuki , Fudou Ryosuke , Iizuka Takashi , Nakajima Daisuke , Okazaki Koei , Shibata Daisuke , Ojika Makoto , Harayama Shigeaki 
Published: July 2008

ABSTRACT
The diversity of type I modular polyketide synthase (PKS) was explored by PCR amplification of DNA encoding ketosynthase and acyltransferase domains in myxobacteria. The sequencing of the amplicons revealed that many PKS genes were distantly related to the published sequences. Thus, myxobacteria may be excellent resources for novel and diverse polyketides.
Probiotic
Lactobacillus plantarum
299v Does Not Counteract Unfavorable Phytohemagglutinin-Induced Changes in the Rat Intestinal Microbiota
Authors: Gross Gabriele , Wildner Jessica , Schonewille Arjan , Rademaker Jan L. W. , van der Meer Roelof , Snel Johannes 
Published: July 2008

ABSTRACT

Application of phytohemagglutinin (PHA) in weaning feed has been suggested to stimulate intestinal epithelium maturation. In this study, PHA strongly affected the fecal bacterial population structure of rats.
Escherichia coli
overgrowth was not prevented by probiotic mannose-adhering
Lactobacillus plantarum
299v. Therefore, use of PHA in weaning feed deserves careful evaluation.
Biological Enrichment of Mycoplasma Agents by Cocultivation with Permissive Cell Cultures
Authors: Volokhov Dmitriy V. , Kong Hyesuk , George Joseph , Anderson Christine , Chizhikov Vladimir E. 
Published: July 2008

ABSTRACT

In this study, we describe our results on the evaluation of the ability of different permissive mammalian cell lines to support the biological enrichment of mycoplasma species known to be bacterial contaminants of cell substrates. The study showed that this approach is able to significantly improve the efficiency of mycoplasma detection based on nucleic acid testing or biochemical technologies (e.g., MycoAlert mycoplasma detection). Of 10 different cell lines (Vero, MDBK, HEK-293, Hep-G2, CV-1, EBTr, WI-38, R9ab, MDCK, and High Five) used in the study, only MDCK cell culture was found to support the efficient growth of all the tested mycoplasmas (
Mycoplasma arginini
,
M. bovis
,
M. fermentans
,
M. gallinaceum
,
M. gallisepticum
,
M. synoviae
,
M. hominis
,
M. hyorhinis
,
M. orale
,
M. salivarium
, and
Acholeplasma laidlawii
) known to be most frequently associated with contamination of cell substrates and cell lines in research laboratories or manufacturing facilities. The infection of MDCK cells with serial dilutions of each mycoplasma species demonstrated that these common cell line contaminants can be detected reliably after 7-day enrichment in MDCK cell culture at contamination levels of 0.05 to 0.25 CFU/ml. The High Five insect cell line was also found to be able to support the efficient growth of most mycoplasma species tested, except for
M. hyorhinis
strain DBS1050. However, mycoplasma growth in insect cell culture was demonstrated to be temperature dependent, and the most efficient growth was observed when the incubation temperature was increased from 28°C to between 35 and 37°C. We believe that this type of mycoplasma enrichment is one of the most promising approaches for improving the purity and safety testing of cell substrates and other cell-derived biologics and pharmaceuticals.
Broad-Host-Range Expression Vectors with Tightly Regulated Promoters and Their Use To Examine the Influence of TraR and TraM Expression on Ti Plasmid Quorum Sensing
Authors: Khan Sharik R. , Gaines Jennifer , Roop R. Martin , Farrand Stephen K. 
Published: July 2008

ABSTRACT

Experiments requiring strong repression and precise control of cloned genes can be difficult to conduct because of the relatively high basal level of expression of currently employed promoters. We report the construction of a family of vectors that contain a reengineered
lacI
q
-
lac
promoter-operator complex in which cloned genes are strongly repressed in the absence of inducer. The vectors, all based on the broad-host-range plasmid pBBR1, are mobilizable and stably replicate at moderate copy number in representatives of the alpha- and gammaproteobacteria. Each vector contains a versatile multiple cloning site that includes an NdeI site allowing fusion of the cloned gene to the initiation codon of
lacZ
α. In each tested bacterium, a
uidA
reporter fused to the promoter was not expressed at a detectable level in the absence of induction but was inducible by 10- to 100-fold, depending on the bacterium. The degree of induction was controllable by varying the concentration of inducer. When the vector was tested in
Agrobacterium tumefaciens
, a cloned copy of the
traR
gene, the product of which is needed at only a few copies per cell, did not confer activity under noninducing conditions. We used this attribute of very tight and variably regulatable control to assess the relative amounts of TraR required to activate the Ti plasmid conjugative transfer system. We identified levels of induction that gave wild-type transfer frequencies, as well as levels that induced correspondingly lower frequencies of transfer. We also used this system to show that the antiactivator TraM sets the level of intracellular TraR required for
tra
gene activation.
Gene Silencing by RNA Interference in the White Rot Fungus
Phanerochaete chrysosporium
Authors: Matityahu Avi , Hadar Yitzhak , Dosoretz Carlos G. , Belinky Paula A. 
Published: July 2008

ABSTRACT

The effectiveness of RNA interference (RNAi) is demonstrated in the lignin-degrading fungus
Phanerochaete chrysosporium
. The manganese-containing superoxide dismutase gene (
MnSOD1
) was used as the target for RNAi. The plasmid constructed for gene silencing contained a transcriptional unit for hairpin RNA expression. Significantly lower
MnSOD
expression at both the mRNA and protein activity levels was detected in RNAi transformants. Furthermore, even though
P. chrysosporium
possesses three copies of the
MnSOD
gene, this RNAi construct was sufficient to decrease the enzymatic activity by as much as 70% relative to control levels. Implementation of the RNAi technique in
P. chrysosporium
provides an alternative genetic tool for studies of gene function, particularly of essential genes or gene families.
Schizosaccharomyces pombe
Noc3 Is Essential for Ribosome Biogenesis and Cell Division but Not DNA Replication
Authors: Houchens Christopher R. , Perreault Audrey , Bachand François , Kelly Thomas J. 
Published: July 2008

ABSTRACT

The initiation of eukaryotic DNA replication is preceded by the assembly of prereplication complexes (pre-RCs) at chromosomal origins of DNA replication. Pre-RC assembly requires the essential DNA replication proteins ORC, Cdc6, and Cdt1 to load the MCM DNA helicase onto chromatin.
Saccharomyces cerevisiae
Noc3 (ScNoc3), an evolutionarily conserved protein originally implicated in 60S ribosomal subunit trafficking, has been proposed to be an essential regulator of DNA replication that plays a direct role during pre-RC formation in budding yeast. We have cloned
Schizosaccharomyces pombe noc3
+
(Sp
noc3
+
), the
S. pombe
homolog of the budding yeast Sc
NOC3
gene, and functionally characterized the requirement for the SpNoc3 protein during ribosome biogenesis, cell cycle progression, and DNA replication in fission yeast. We showed that fission yeast SpNoc3 is a functional homolog of budding yeast ScNoc3 that is essential for cell viability and ribosome biogenesis. We also showed that SpNoc3 is required for the normal completion of cell division in fission yeast. However, in contrast to the proposal that ScNoc3 plays an essential role during DNA replication in budding yeast, we demonstrated that fission yeast cells do enter and complete S phase in the absence of SpNoc3, suggesting that SpNoc3 is not essential for DNA replication in fission yeast.
Evolution of theRhodococcus equi vapPathogenicity Island Seen through Comparison of Host-AssociatedvapAandvapBVirulence Plasmids
Authors: Letek Michal , Ocampo-Sosa Alain A. , Sanders Mandy , Fogarty Ursula , Buckley Tom , Leadon Desmond P. , González Patricia , Scortti Mariela , Meijer Wim G. , Parkhill Julian , Bentley Stephen , Vázquez-Boland José A. 
Published: July 2008

ABSTRACTThe pathogenic actinomyceteRhodococcus equiharbors different types of virulence plasmids associated with specific nonhuman hosts. We determined the complete DNA sequence of avapB+plasmid, typically associated with pig isolates, and compared it with that of the horse-specificvapA+plasmid type. pVAPB1593, a circular 79,251-bp element, had the same housekeeping backbone as thevapA+plasmid but differed over an ≈22-kb region. This variable region encompassed thevappathogenicity island (PAI), was clearly subject to selective pressures different from those affecting the backbone, and showed major genetic rearrangements involving thevapgenes. The pVAPB1593 PAI harbored five differentvapgenes (vapBandvapJto -M, withvapKpresent in two copies), which encoded products differing by 24 to 84% in amino acid sequence from the six full-lengthvapA+plasmid-encoded Vap proteins, consistent with a role for the specificvapgene complement inR. equihost tropism. Sequence analyses, including interpolated variable-order motifs for detection of alien DNA and reconstruction of Vap family phylogenetic relationships, suggested that thevapPAI was acquired by an ancestor plasmid via lateral gene transfer, subsequently evolving byvapgene duplication and sequence diversification to give different (host-adapted) plasmids. TheR. equivirulence plasmids belong to a new family of actinobacterial circular replicons characterized by an ancient conjugative backbone and a horizontally acquired niche-adaptive plasticity region.
'This Chapel is a Sanctuary': Another Place or a Place for the Other?
Authors: Nolan Steve 
Published: July 2008

AbstractTabloid reporting about the removal of crosses from hospital chapels and the banning of Bibles on wards highlights a perception that English cultural identity is under threat by concessions made to minority groups, often characterized as 'political correctness gone mad'. A claim frequently made is that Britain is 'a Christian country', and this article argues that this idea, and its corollary that it is natural and right for Christian symbolism to have precedence in the sacred/spiritual spaces of healthcare institutions, acts as what Lacan and Žižek term a 'master-signifier'. As such, I argue that the marginalization of cultural representation—the symbolizing of cultural/religious values that legitimates the presence of minority religions/cultures—is an important factor contributing to the inequality of access to healthcare in general and palliative care in particular.
Stars and Compasses: Hermeneutical Guides for Public Theology
Authors: Thomson Heather 
Published: July 2008

AbstractIt is the concern of this article that some definitions of public theology allow apartheid and Nazism to be counted as public theology. According to these, Osama Bin Laden could be our greatest, most influential contemporary public theologian. There are lines that must be drawn outside of which we should not go in defining and promoting public theology. To discuss this, I employ the language of 'necessary and sufficient conditions'. It is necessary to define 'public' and 'theology'. What more needs to be said for sufficient conditions to be met? In considering this, hermeneutical guides are sought—stars and compasses—so that the thinking and practice of public theology meets the sufficient conditions of peace-making, justice-seeking, opting for the afflicted and honouring all.
Absence of diffuse cervical cord tissue damage in early, non-disabling relapsing-remitting MS: a preliminary study
Authors: Rovaris M , Judica E , Ceccarelli A , Ghezzi A , Martinelli V , Comi G , Filippi M 
Published: July 2008

Background Magnetization transfer (MT) magnetic resonance imaging (MRI) can provide quantitative information about the severity of tissue damage in the cervical cord of patients with multiple sclerosis (MS). MT MRI-derived measures of cord damage are correlated with the severity of disease-related locomotor disability. Objectives The objective of this study was to investigate whether MT MRI-detectable cervical cord damage is present in early relapsing-remitting (RR) MS. Subjects and methods We studied 23 patients with ‘early’ RR MS (i.e., with a disease duration shorter than 5 years) and 10 age-matched healthy control subjects. During a single session, the following sequences were acquired using a 1.5 T scanner: (a) brain dual-echo turbo spin echo; (b) cervical cord fast short-tau inversion recovery; (c) cervical cord gradient echo, without and with MT pulse. Brain T2 lesion volume was measured. Cervical cord lesions were counted and normalized histograms of cord MT ratio (MTR) were produced. Results One or more cervical cord lesions were found in nine patients (39%). The average cord MTR and the mean histogram peak height values did not differ between patients and controls. There was no significant correlation between brain T2 lesion volume and cervical cord MTR histogram-derived metrics. Conclusions Cervical cord tissue damage seems to be limited to macroscopic lesions in patients with early, non-disabling RR MS. Longitudinal studies are warranted to define the dynamics of MS-related cord damage accumulation over time later on in the course of the disease.
Methylation of class II transactivator gene promoter IV is not associated with susceptibility to Multiple Sclerosis
Authors: Ramagopalan Sreeram V , Dyment David A , Morrison Katie M , Herrera Blanca M , DeLuca Gabriele C , Lincoln Matthew R , Orton Sarah M , Handunnetthi Lahiru , Chao Michael J , Sadovnick A Dessa , Ebers George C 
Published: July 2008

Abstract

Background
Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the MHC2TA promoter pIV could contribute to MS disease aetiology.

Methods
In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the MHC2TA promoter IV was sequenced and analysed by methylation specific PCR.

Results
No methylation or sequence variation of the MHC2TA promoter pIV was found.

Conclusion
The results of this study cannot support the notion that methylation of the pIV promoter of MHC2TA contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.
Gemcitabine based combination chemotherapy in advanced pancreatic cancer-indirect comparison
Authors: Sultana Asma , Ghaneh Paula , Cunningham David , Starling Naureen , Neoptolemos John P , Smith Catrin Tudur 
Published: July 2008

Abstract

Background
Recent meta-analyses have found a survival advantage with gemcitabine based combinations over single agent gemcitabine in patients with advanced pancreatic cancer. There is paucity of evidence in the form of direct head-to-head randomised controlled trials to determine which combinations are to be preferred.

Method
Using the adjusted indirect comparison method proposed by Bucher et al, we have assessed randomised controlled trials of four gemcitabine based combinations namely gemcitabine plus a platinum compound or 5-fluorouracil or irinotecan or capecitabine.

Results
No particular combination was significantly superior to another, but the indirect evidence suggests some important trends.

Conclusion
The strongest trends on indirect comparison are towards favouring gemcitabine plus capecitabine or gemcitabine plus a platinum compound over gemcitabine plus irinotecan, and to a lesser degree, over gemcitabine plus 5-fluorouracil.
Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury
Authors: Kennedy Muiris T , Higgins Brendan D , Costello Joseph F , Curtin William A , Laffey John G 
Published: July 2008

AbstractBackgroundHypertonic saline (HTS) reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury.MethodsAdult male Sprague Dawley rats were used in all experiments.Series 1examined the potential for HTS to reduce the severity of evolving oleic acid (OA) induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12) or hypertonic saline (HTS, n = 12), and the extent of lung injury assessed after 6 hours.Series 2examined the potential for HTS to enhance the resolution of oleic acid (OA) induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6) or hypertonic saline (HTS, n = 6), and the extent of lung injury assessed after 6 hours.ResultsInSeries I, HTS significantly reduced bronchoalveolar lavage (BAL) neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 103cells.ml-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, inSeries 2, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 103cells.ml-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml-1].ConclusionThese findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.
Congenital long QT syndrome
Authors: Crotti Lia , Celano Giuseppe , Dagradi Federica , Schwartz Peter J 
Published: July 2008

Abstract
Congenital long QT syndrome (LQTS) is a hereditary cardiac disease characterized by a prolongation of the QT interval at basal ECG and by a high risk of life-threatening arrhythmias. Disease prevalence is estimated at close to 1 in 2,500 live births.
The two cardinal manifestations of LQTS are syncopal episodes, that may lead to cardiac arrest and sudden cardiac death, and electrocardiographic abnormalities, including prolongation of the QT interval and T wave abnormalities. The genetic basis of the disease was identified in the mid-nineties and all the LQTS genes identified so far encode cardiac ion channel subunits or proteins involved in modulating ionic currents. Mutations in these genes (KCNQ1, KCNH2, KCNE1, KCNE2, CACNA1c, CAV3, SCN5A, SCN4B) cause the disease by prolonging the duration of the action potential. The most prevalent LQTS variant (LQT1) is caused by mutations in the KCNQ1 gene, with approximately half of the genotyped patients carrying KCNQ1 mutations.
Given the characteristic features of LQTS, the typical cases present no diagnostic difficulties for physicians aware of the disease. However, borderline cases are more complex and require the evaluation of various electrocardiographic, clinical, and familial findings, as proposed in specific diagnostic criteria. Additionally, molecular screening is now part of the diagnostic process.
Treatment should always begin with β-blockers, unless there are valid contraindications. If the patient has one more syncope despite a full dose β-blockade, left cardiac sympathetic denervation (LCSD) should be performed without hesitation and implantable cardioverter defibrillator (ICD) therapy should be considered with the final decision being based on the individual patient characteristics (age, sex, clinical history, genetic subgroup including mutation-specific features in some cases, presence of ECG signs – including 24-hour Holter recordings – indicating high electrical instability).
The prognosis of the disease is usually good in patients that are correctly diagnosed and treated. However, there are a few exceptions: patients with Timothy syndrome, patients with Jervell Lange-Nielsen syndrome carrying KCNQ1 mutations and LQT3 patients with 2:1 atrio-ventricular block and very early occurrence of cardiac arrhythmias.