bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effector memory T‐cell frequencies in relation to tumour stage, location and HPV status in HNSCC patients
Authors: Turksma AW , Bontkes HJ , van den Heuvel H , de Gruijl TD , von Blomberg BME , Braakhuis BJM , Leemans CR , Bloemena E , Meijer CJLM , Hooijberg E 
Published: October 2012

BackgroundThe immune system plays an important role in tumour immune surveillance. Head and neck squamous cell carcinoma patients are often immune compromised.ObjectiveTo chart the baseline levels of T‐cell subpopulation frequencies in patients with cancer prior to treatment.Subjects and methodsBlood samples of patients were taken at the time of diagnosis, analysed with flowcytometry and compared with blood samples of healthy donors.ResultsCompared to healthy donors, a significant shift from naive to effector memory T cells was observed. This effect was most prominent in stage II patients. A similar shift from naive to effector memory T cells was noted in patients with oropharynx or larynx squamous cell carcinomas. Furthermore, the percentage of effector memory and effector T cells was higher in the group of patients with human papillomavirus‐positive oropharyngeal squamous cell carcinomas, compared with patients with human papillomavirus‐negative tumours, suggestive of virus‐induced T‐cell activation.ConclusionHere, we provide a simple and easily implementable tool to document T lymphocyte subsets in the peripheral blood of head and neck cancer patients, which might be useful for prognosis and/or therapy response prediction.
Gene targeting in maize by somatic ectopic recombination
Authors: Ayar Ayhan , Wehrkamp‐Richter Sophie , Laffaire Jean‐Baptiste , Le Goff Samuel , Levy Julien , Chaignon Sandrine , Salmi Hajer , Lepicard Alexandra , Sallaud Christophe , Gallego Maria E. , White Charles I. , Paul Wyatt 
Published: October 2012

SummaryLow transformation efficiency and high background of non‐targeted events are major constraints to gene targeting in plants. We demonstrate here applicability in maize of a system that reduces the constraint from transformation efficiency. The system requires regenerable transformants in which all of the following elements are stably integrated in the genome: (i) donor DNA with the gene of interest adjacent to sequence for repair of a defective selectable marker, (ii) sequence encoding a rare‐cutting endonuclease such as I‐SceI, (iii) a target locus (TL) comprising the defective selectable marker and I‐SceI cleavage site. Typically, this requires additional markers for the integration of the donor and target sequences, which may be assembled through cross‐pollination of separate transformants. Inducible expression of I‐SceI then cleaves the TL and facilitates homologous recombination, which is assayed by selection for the repaired marker. We used bar and gfp markers to identify assembled transformants, a dexamethasone‐inducible I‐SceI::GR protein, and selection for recombination events that restored an intact nptII. Applying this strategy to callus permitted the selection of recombination into the TL at a frequency of 0.085% per extracted immature embryo (29% of recombinants). Our results also indicate that excision of the donor locus (DL) through the use of flanking I‐SceI cleavage sites may be unnecessary, and a source of unwanted repair events at the DL. The system allows production, from each assembled transformant, of many cells that subsequently can be treated to induce gene targeting. This may facilitate gene targeting in plant species for which transformation efficiencies are otherwise limiting.
Hydrogen gas acts as a novel bioactive molecule in enhancing plant tolerance to paraquat‐induced oxidative stress via the modulation of heme oxygenase‐1 signalling system
Authors: JIN QIJIANG , ZHU KAIKAI , CUI WEITI , XIE YANJIE , HAN BIN , SHEN WENBIAO 
Published: October 2012

ABSTRACTHydrogen gas (H2) was recently proposed as a novel antioxidant and signalling molecule in animals. However, the physiological roles of H2 in plants are less clear. Here, we showed that exposure of alfalfa seedlings to paraquat stress increased endogenous H2 production. When supplied with exogenous H2 or the heme oxygenase‐1 (HO‐1)‐inducer hemin, alfalfa plants displayed enhanced tolerance to oxidative stress induced by paraquat. This was evidenced by alleviation of the inhibition of root growth, reduced lipid peroxidation and the decreased hydrogen peroxide and superoxide anion radical levels. The activities and transcripts of representative antioxidant enzymes were induced after exposure to either H2 or hemin. Further results showed that H2 pretreatment could dramatically increase levels of the MsHO‐1 transcript, levels of the protein it encodes and HO‐1 activity. The previously mentioned H2‐mediated responses were specific for HO‐1, given that the potent HO‐1‐inhibitor counteracted the effects of H2. The effects of H2 were reversed after the addition of an aqueous solution of 50% carbon monoxide (CO). We also discovered enhanced tolerance of multiple environmental stresses after plants were pretreated with H2. Together, these results suggested that H2 might function as an important gaseous molecule that alleviates oxidative stress via HO‐1 signalling.
Rehabilitation of the Geriatric Dialysis Patient
Authors: Farragher Janine , Jassal Sarbjit Vanita 
Published: October 2012

AbstractDialysis is offered to patients with end‐stage renal disease as a life‐sustaining therapy. However, studies have shown that elderly patients experience high rates of functional disability, hospitalization, institutionalization, and mortality on chronic dialysis therapy, and that the initiation of dialysis is in fact associated with an acceleration in functional decline. These findings have sparked debate about the utility of dialysis for elderly renal patients. In this article, it is proposed that geriatric rehabilitation can prevent, reverse or delay the onset of functional disability and associated adverse outcomes in older dialysis patients, and thus should be incorporated routinely into standard geriatric dialysis care. We outline the causes of disability in elderly dialysis patients, and demonstrate the potential impact of rehabilitation using a case scenario. Models of rehabilitation that have been shown to be effective in improving outcomes for elderly renal and nonrenal populations, including inpatient rehabilitation, exercise training, falls prevention, and home‐based models, are reviewed.
Stepwise Development of a Homozygous S80P Substitution in Fks1p, Conferring Echinocandin Resistance in Candida tropicalis
Authors: Jensen Rasmus Hare , Johansen Helle Krogh , Arendrup Maiken Cavling 
Published: October 2012

ABSTRACT

Three
Candida tropicalis
isolates were obtained from a patient with acute lymphoblastic leukemia. The first isolate was susceptible to all drug classes, while isolates 2 and 3, obtained after 8 and 8.5 weeks of caspofungin treatment, respectively, were resistant to the three echinocandins. Multilocus sequence genotyping suggested a clonal relation among all isolates.
FKS1
sequencing revealed a stepwise development of a heterozygous and finally a homozygous mutation, leading to S80S/P and S80P amino acid substitutions.
Innate Aminoglycoside Resistance of Achromobacter xylosoxidans Is Due to AxyXY-OprZ, an RND-Type Multidrug Efflux Pump
Authors: Bador Julien , Amoureux Lucie , Blanc Emmanuel , Neuwirth Catherine 
Published: October 2012

ABSTRACT

Achromobacter xylosoxidans
is an innately multidrug-resistant pathogen which is emerging in cystic fibrosis (CF) patients. We characterized a new resistance-nodulation-cell division (RND)-type multidrug efflux pump, AxyXY-OprZ. This system is responsible for the intrinsic high-level resistance of
A. xylosoxidans
to aminoglycosides (tobramycin, amikacin, and gentamicin). Furthermore, it can extrude cefepime, carbapenems, some fluoroquinolones, tetracyclines, and erythromycin. Some of the AxyXY-OprZ substrates are major components widely used to treat pulmonary infections in CF patients.
Evaluation of Caspofungin Susceptibility Testing by the New Vitek 2 AST-YS06 Yeast Card Using a Unique Collection of
FKS
Wild-Type and Hot Spot Mutant Isolates, Including the Five Most Common Candida Species
Authors: Astvad Karen M. , Perlin David S. , Johansen Helle K. , Jensen Rasmus H. , Arendrup Maiken C. 
Published: October 2012

ABSTRACT

FKS
mutant isolates associated with breakthrough or failure cases are emerging in clinical settings. Discrimination of these from wild-type (wt) isolates in a routine laboratory setting is complicated. We evaluated the ability of caspofungin MIC determination using the new Vitek 2 AST-Y06 yeast susceptibility card to correctly identify the
fks
mutants from wt isolates and compared the performance to those of the CLSI and EUCAST reference methods. A collection of 98
Candida
isolates, including 31
fks
hot spot mutants, were included. Performance was evaluated using the
FKS
genotype as the “gold standard” and compared to those of the CLSI and EUCAST methodologies. The categorical agreement for Vitek 2 was 93.9%, compared to 88.4% for the CLSI method and 98.7% for the EUCAST method. Vitek 2 misclassified 19.4% (6/31) of the
fks
mutant isolates as susceptible, in contrast to <4% for each of the reference methods. The overall essential agreement between the CLSI method and Vitek 2 MICs was 92.6% (88/95) but was substantially lower for
fks
mutant isolates (78.6% [22/28]). Correct discrimination between susceptible and intermediate
Candida glabrata
isolates was not possible, as the revised species-specific susceptibility breakpoint was not included in the Vitek 2 detection range (MIC of ≤0.250 to ≥4 mg/liter). In conclusion, the Vitek 2 allowed correct categorization of all wt isolates as susceptible. However, despite an acceptable categorical agreement, it failed to reliably classify isolates harboring
fks
hot spot mutations as intermediate or resistant, which was in part due to the fact that the detection range did not span the susceptibility breakpoint for
C. glabrata
.
Wide Dissemination of GES-Type Carbapenemases in Acinetobacter baumannii Isolates in Kuwait
Authors: Bonnin Rémy A. , Rotimi Vincent O. , Al Hubail Mona , Gasiorowski Elise , Al Sweih Noura , Nordmann Patrice , Poirel Laurent 
Published: October 2012

ABSTRACT

Acinetobacter baumannii
is an opportunistic pathogen that is an important source of nosocomial infections. Production of extended-spectrum β-lactamases (ESBLs) of the GES type in
A. baumannii
has been increasingly reported, and some of these GES-type enzymes possess some carbapenemase activity. Our aim was to analyze the resistance determinants and the clonal relationships of carbapenem-nonsusceptible
A. baumannii
clinical isolates recovered from hospitals in Kuwait. A total of 63 isolates were analyzed, and all were found to be positive for
bla
GES
-type genes. One isolate harbored the
bla
GES-14
gene encoding an ESBL with significant carbapenemase activity, whereas the other isolates harbored the
bla
GES-11
ESBL gene. Thirty-three isolates coharbored the
bla
OXA-23
and
bla
GES-11
genes. Analyses of the genetic locations indicated that the
bla
GES-11/-14
genes were plasmid located. It is noteworthy that the
bla
OXA-23
and
bla
GES-11
genes were colocated onto a single plasmid. Nine different pulsotypes were observed among the 63 isolates. This study showed the emergence of GES-type ESBLs in
A. baumannii
in Kuwait, further suggesting that the Middle East region might be a reservoir for carbapenemase-producing
A. baumannii
.
Pharmacodynamics of a Simulated Single 1,200-Milligram Dose of Oritavancin in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model of Methicillin-Resistant Staphylococcus aureus Infection
Authors: Belley Adam , Arhin Francis F. , Sarmiento Ingrid , Deng Hong , Rose Warren , Moeck Greg 
Published: October 2012

ABSTRACT

The safety and efficacy of a single 1,200-mg dose of the lipoglycopeptide oritavancin are currently being investigated in two global phase 3 studies of acute bacterial skin and skin structure infections. In this study, an
in vitro
pharmacokinetic/pharmacodynamic model was established to compare the free-drug pharmacodynamics associated with a single 1,200-mg dose of oritavancin to once-daily dosing with daptomycin at 6 mg/kg of body weight and twice-daily dosing with vancomycin at 1,000 mg against three methicillin-resistant
Staphylococcus aureus
(MRSA) strains over 72 h. The area under the bacterial-kill curve (AUBKC) was used to assess the antibacterial effect of each dosing regimen at 24 h (AUBKC
0-24
), 48 h (AUBKC
0-48
), and 72 h (AUBKC
0-72
). The rapid bactericidal activities of oritavancin and daptomycin contributed to lower AUBKC
0-24
s for the three MRSA strains than with vancomycin (
P
< 0.05, as determined by analysis of variance [ANOVA]). Oritavancin exposure also resulted in a lower AUBKC
0-48
and AUBKC
0-72
against one MRSA strain and a lower AUBKC
0-48
for another strain than did vancomycin exposure (
P
< 0.05). Furthermore, daptomycin exposure resulted in a lower AUBKC
0-48
and AUBKC
0-72
for one of the MRSA isolates than did vancomycin exposure (
P
< 0.05). Lower AUBKC
0-24
s for two of the MRSA strains (
P
< 0.05) were obtained with oritavancin exposure than with daptomycin. Thus, the antibacterial effect from the single-dose regimen of oritavancin is as effective as that from either once-daily dosing with daptomycin or twice-daily dosing with vancomycin against the MRSA isolates tested in an
in vitro
pharmacokinetic/pharmacodynamic model over 72 h. These results provide further justification to assess the single 1,200-mg dose of oritavancin for treatment of acute bacterial skin and skin structure infections.
Elevated Chitin Content Reduces the Susceptibility of Candida Species to Caspofungin
Authors: Walker Louise A. , Gow Neil A. R. , Munro Carol A. 
Published: October 2012

ABSTRACT

The echinocandin antifungal drugs inhibit synthesis of the major fungal cell wall polysaccharide β(1,3)-glucan. Echinocandins have good efficacy against
Candida albicans
but reduced activity against other
Candida
species, in particular
Candida parapsilosis
and
Candida guilliermondii
. Treatment of
Candida albicans
with a sub-MIC level of caspofungin has been reported to cause a compensatory increase in chitin content and to select for sporadic echinocandin-resistant
FKS1
point mutants that also have elevated cell wall chitin. Here we show that elevated chitin in response to caspofungin is a common response in various
Candida
species. Activation of chitin synthesis was observed in isolates of
C. albicans
,
Candida tropicalis
,
C. parapsilosis
, and
C. guilliermondii
and in some isolates of
Candida krusei
in response to caspofungin treatment. However,
Candida glabrata
isolates demonstrated no exposure-induced change in chitin content. Furthermore, isolates of
C. albicans
,
C. krusei
,
C. parapsilosis
, and
C. guilliermondii
which were stimulated to have higher chitin levels via activation of the calcineurin and protein kinase C (PKC) signaling pathways had reduced susceptibility to caspofungin. Isolates containing point mutations in the
FKS1
gene generally had higher chitin levels and did not demonstrate a further compensatory increase in chitin content in response to caspofungin treatment. These results highlight the potential of increased chitin synthesis as a potential mechanism of tolerance to caspofungin for the major pathogenic
Candida
species.
pSK41-Like Plasmid Is Necessary for Inc18-Like
vanA
Plasmid Transfer from Enterococcus faecalis to Staphylococcus aureus
In Vitro
Authors: Zhu Wenming , Clark Nancye , Patel Jean B. 
Published: October 2012

ABSTRACT

Vancomycin-resistant
Staphylococcus aureus
(VRSA) is thought to result from the
in vivo
conjugative transfer of a
vanA
plasmid from an
Enterococcus
sp. to
S. aureus
. We studied bacterial isolates from VRSA cases that occurred in the United States to identify microbiological factors which may contribute to this plasmid transfer. First, vancomycin-susceptible, methicillin-resistant
S. aureus
(MRSA) isolates from five VRSA cases were tested for their ability to accept foreign DNA by conjugation in mating experiments with
Enterococcus faecalis
JH2-2 containing pAM378, a pheromone-response conjugative plasmid. All of the MRSA isolates accepted the plasmid DNA with similar transfer efficiencies (∼10
−7
/donor CFU) except for one isolate, MRSA8, for which conjugation was not successful. The MRSA isolates were also tested as recipients in mating experiments between an
E. faecalis
isolate with an Inc18-like
vanA
plasmid that was isolated from a VRSA case patient. Conjugative transfer was successful for 3/5 MRSA isolates. Successful MRSA recipients carried a pSK41-like plasmid, a staphylococcal conjugative plasmid, whereas the two unsuccessful MRSA recipients did not carry pSK41. The transfer of a pSK41-like plasmid from a successful MRSA recipient to the two unsuccessful recipients resulted in conjugal transfer of the Inc18-like
vanA
plasmid from
E. faecalis
at a frequency of 10
−7
/recipient CFU. In addition, conjugal transfer could be achieved for pSK41-negative MRSA in the presence of a cell-free culture filtrate from
S. aureus
carrying a pSK41-like plasmid at a frequency of 10
−8
/recipient CFU. These results indicated that a pSK41-like plasmid can facilitate the transfer of an Inc18-like
vanA
plasmid from
E. faecalis
to
S. aureus
, possibly via an extracellular factor produced by pSK41-carrying isolates.
Daptomycin Concentrations in Valve Tissue and Vegetation in Patients with Bacterial Endocarditis
Authors: Tascini Carlo , Di Paolo Antonello , Poletti Roberta , Flammini Sarah , Emdin Michele , Ciullo Ilaria , Tagliaferri Enrico , Moter Annette , Menichetti Francesco 
Published: October 2012

ABSTRACT

In a patient with mitral-aortic native-valve
Streptococcus oralis
endocarditis, daptomycin concentrations in aortic and mitral valves were 8.6 and 30.8 μg/g, respectively, and 26 μg/g in the mitral vegetation. In the case of porcine-aortic-valve
Staphylococcus epidermidis
endocarditis, the daptomycin concentrations were 53.1 μg/g in the valve and 18.1 μg/g in perivalvular tissues. Daptomycin achieved apparently adequate tissue concentrations.
S. epidermidis
was eradicated, whereas
Streptococcus oralis
persisted, and its daptomycin MIC displayed a 4-fold increase.
A Purified Capsular Polysaccharide Markedly Inhibits Inflammatory Response during Endotoxic Shock
Authors: Piccioni M. , Monari C. , Kenno S. , Pericolini E. , Gabrielli E. , Pietrella D. , Perito S. , Bistoni F. , Kozel T. R. , Vecchiarelli A. 
Published: October 2012

ABSTRACT

Capsular material of the opportunistic fungus
Cryptococcus neoformans
is composed mainly of a polysaccharide named glucuronoxylomannan (GXM). In this study, the effects of GXM were analyzed in an
in vivo
experimental system of lipopolysaccharide (LPS)-induced shock. Endotoxic shock was induced in mice by a single intraperitoneal injection of LPS from
Escherichia coli
. GXM treatment reduced the mortality of mice at early stages. Mice treated with LPS alone showed markedly increased plasma levels of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6, whereas mice that were also treated with GXM showed significantly lower plasma levels of these cytokines. This effect was related to a marked suppression of Akt and IκBα activation. Importantly, the inhibitory effect of GXM on proinflammatory cytokine secretion was reproduced by treatment with wortmannin, an inhibitor of the Akt transcription pathway. Our results indicate that GXM has a beneficial effect on endotoxic shock, resulting in a significant increase in the rate of survival by dampening the hyperinflammatory response.
Innate Immune Response to Streptococcus iniae Infection in Zebrafish Larvae
Authors: Harvie Elizabeth A. , Green Julie M. , Neely Melody N. , Huttenlocher Anna 
Published: October 2012

ABSTRACTStreptococcus iniaecauses systemic infection characterized by meningitis and sepsis. Here, we report a larval zebrafish model ofS. iniaeinfection. Injection of wild-typeS. iniaeinto the otic vesicle induced a lethal infection by 24 h postinfection. In contrast, anS. iniaemutant deficient in polysaccharide capsule (cpsAmutant) was not lethal, with greater than 90% survival at 24 h postinfection. Live imaging demonstrated that both neutrophils and macrophages were recruited to localized otic infection with mutant and wild-typeS. iniaeand were able to phagocytose bacteria. Depletion of neutrophils and macrophages impaired host survival following infection with wild-typeS. iniaeand thecpsAmutant, suggesting that leukocytes are critical for host survival in the presence of both the wild-type and mutant bacteria. However, zebrafish larvae with impaired neutrophil function but normal macrophage function had increased susceptibility to wild-type bacteria but not thecpsAmutant. Taking these findings together, we have developed a larval zebrafish model ofS. iniaeinfection and have found that although neutrophils are important for controlling infection with wild-typeS. iniae, neutrophils are not necessary for host defense against thecpsAmutant.
Characterization of the AggR Regulon in Enteroaggregative Escherichia coli
Authors: Morin Nicholas , Santiago Araceli E. , Ernst Robert K. , Guillot Stacey J. , Nataro James P. 
Published: October 2012

ABSTRACT

AggR is a transcriptional regulator of enteroaggregative
Escherichia coli
(EAEC) and has been proposed as the defining factor for typical EAEC strains. Expression of multiple putative virulence factors, including the aggregative adherence fimbriae (AAF), dispersin, the dispersin translocator Aat, and the Aai type VI secretion system, have been found to be regulated by AggR. Here, we confirm the existence of at least 44 AggR-regulated genes using DNA microarray and real-time quantitative reverse transcription-PCR (qRT-PCR); these genes include chromosomal and plasmid-borne loci and 19 previously unsuspected genes. Two previously uncharacterized virulence plasmid-encoded open reading frames (ORFs) (designated ORF3 and ORF4) exhibit significant identity with isoprenoid biosynthesis genes of
Bacteria
and
Archaea
. The predicted ORF4 product is closely related to isopentenyl isomerase (IDI) enzymes, whereas the predicted product of the adjacent ORF3 exhibits an aspartate-rich region that is common among
trans
-isoprenyl phosphate synthases. We show that mutations in these ORFs confer changes in bacterial surface properties. AggR coordinately controls expression of a large number of EAEC genes.
Transcriptional Responses of Uropathogenic Escherichia coli to Increased Environmental Osmolality Caused by Salt or Urea
Authors: Withman Benjamin , Gunasekera Thusitha S. , Beesetty Pavani , Agans Richard , Paliy Oleg 
Published: October 2012

ABSTRACTUropathogenicEscherichia coli(UPEC) is the most common causative agent of urinary tract infections in humans. The majority of urinary infections develop via ascending route through the urethra, where bacterial cells come in contact with human urine prior to reaching the bladder or kidneys. Since urine contains significant amounts of inorganic ions and urea, it imposes osmotic and denaturing stresses on bacterial cells. In this study, we determined the transcriptional adaptive responses of UPEC strain CFT073 to the presence of 0.3 M NaCl or 0.6 M urea in the growth medium. The cell responses to these two osmolytes were drastically different. Although most of the genes of the osmotically inducible regulon were overexpressed in medium with salt, urea failed to stimulate osmotic stress response. At the same time, UPEC colonization genes encoding type 1 and F1C fimbriae and capsule biosynthesis were transcriptionally induced in the presence of urea but did not respond to increased salt concentration. We speculate that urea can potentially be sensed by uropathogenic bacteria to initiate infection program. In addition, several molecular chaperone genes were overexpressed in the presence of urea, whereas adding NaCl to the medium led to an upregulation of a number of anaerobic metabolism pathways.