bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protoporphyrin IX‐Functionalized AgSiO2 Core–Shell Nanoparticles: Plasmonic Enhancement of Fluorescence and Singlet Oxygen Production
Authors: Lismont Marjorie , Dreesen Laurent , Heinrichs Benoît , Páez Carlos A. 
Published: December 2015

AbstractMetal‐enhanced processes arising from the coupling of a dye with metallic nanoparticles (NPs) have been widely reported. However, few studies have simultaneously investigated these mechanisms from the viewpoint of dye fluorescence and photoactivity. Herein, protoporphyrin IX (PpIX) is grafted onto the surface of silver core silica shell NPs in order to investigate the effect of silver (Ag) localized surface plasmon resonance (LSPR) on PpIX fluorescence and PpIX singlet oxygen (1O2) production. Using two Ag core sizes, we report a systematic study of these photophysical processes as a function of silica (SiO2) spacer thickness, LSPR band position and excitation wavelength. The excitation of Ag NP LSPR, which overlaps the PpIX absorption band, leads to the concomitant enhancement of PpIX fluorescence and 1O2 production independently of the Ag core size, but in a more pronounced way for larger Ag cores. These enhancements result from the increase in the PpIX excitation rate through the LSPR excitation and decrease when the distance between PpIX and Ag NPs increases. A maximum fluorescence enhancement of up to 14‐fold, together with an increase in photogenerated 1O2 production of up to five times are obtained using 100 nm Ag cores coated with a 5 nm thick silica coating.
Immunopathology in Taenia solium neurocysticercosis
Authors: Fleury A. , Cardenas G. , Adalid‐Peralta L. , Fragoso G. , Sciutto E. 
Published: December 2015

SummaryNeurocysticercosis is a clinically and radiologically heterogeneous disease, ranging from asymptomatic infection to a severe, potentially fatal clinical picture. The intensity and extension of the parasite‐elicited inflammatory reaction is a key factor for such variability. The main features of the inflammatory process found in the brain and in the peripheral blood of neurocysticercosis patients will be discussed in this review, and the factors involved in its modulation will be herein presented.
Elevated CO2 enhances photosynthetic efficiency, ion uptake and antioxidant activity of Gynura bicolor DC. grown in a porous‐tube nutrient delivery system under simulated microgravity
Authors: Wang M. , Liu H. , Dong C. , Fu Y. , Liu H. 
Published: December 2015

AbstractIt is well known that plants can grow under space conditions, however, perturbations of many biological phenomena have been highlighted due to the effect of altered gravity and its possible interaction with other factors (e.g., CO2, ion radiation, etc. Our aim was to test whether elevated CO2 could provide ‘protection’ to Gynura bicolor against the damaging effects of simulated microgravity (SM) on photosynthesis, ion uptake and antioxidant activity. As compared to G. bicolor grown in ambient CO2 with no SM (ACO2), growth and yield of the plants increased under elevated ambient CO2 with no SM (ECO2) and decreased under ACO2+SM, whereas there was no significant effect on ECO2+SM. Reductions in the content of Chl a, carotenoids and Chl a+b were 17.9%, 20.7% and 17.9% under ACO2+SM, respectively, but under ECO2 there was a significant effect on all photosynthetic pigments except Chl b, compared to ACO2. Photosynthesis was improved under ECO2 with SM and such an improvement was associated with improved water use efficiency and instantaneous carboxylation efficiency. Furthermore, SM caused a reduction in ion absorption rate, except for Ca2+, while ECO2 increased the uptake rate. Finally, the activity of SOD, POD and the content of MDA and H2O2 were enhanced under SM treatments and were highest in ACO2+SM. In contrast, T‐AOC activity and GSH content significantly declined in ACO2+SM compared to other treatments. These results suggest that ACO2 is not sufficient to counteract SM impact, but the increase is usually caused by improvement in CO2 nutrition in ECO2+SM in comparison with ACO2+SM.
Correlation of β-Lactamase Production and Colistin Resistance among Enterobacteriaceae Isolates from a Global Surveillance Program
Authors: Bradford Patricia A. , Kazmierczak Krystyna M. , Biedenbach Douglas J. , Wise Mark G. , Hackel Meredith , Sahm Daniel F. 
Published: December 2015

ABSTRACT

The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram-negative bacterial infections has contributed to the global dissemination of carbapenem-resistant
Enterobacteriaceae
(CRE). Serine and metallo-β-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries, necessitating the use of older classes of agents, such as colistin. A total of 19,719 isolates of
Enterobacteriaceae
(excluding
Proteeae
and
Serratia
spp., which have innate resistance to colistin) were collected from infected patients during 2012 and 2013 in a global surveillance program and tested for antimicrobial susceptibility using CLSI methods. Isolates of CRE were characterized for carbapenemases and extended-spectrum β-lactamases (ESBLs) by PCR and sequencing. Using EUCAST breakpoints, the rate of colistin susceptibility was 98.4% overall, but it was reduced to 88.0% among 482 carbapenemase-positive isolates. Colistin susceptibility was higher among MBL-positive isolates (92.6%) than those positive for a KPC (87.9%) or OXA-48 (84.2%). Of the agents tested, only tigecycline (MIC
90
, 2 to 4 μg/ml) and aztreonam-avibactam (MIC
90
, 0.5 to 1 μg/ml) consistently tested with low MIC values against colistin-resistant, ESBL-positive, and carbapenemase-positive isolates. Among the 309 (1.6%) colistin-resistant isolates from 10 species collected in 38 countries, 58 carried a carbapenemase that included KPCs (38 isolates), MBLs (6 isolates), and OXA-48 (12 isolates). These isolates were distributed globally (16 countries), and 95% were
Klebsiella pneumoniae
. Thirty-nine (67.2%) isolates carried additional ESBL variants of CTX-M, SHV, and VEB. This sample of
Enterobacteriaceae
demonstrated a low prevalence of colistin resistance overall. However, the wide geographic dispersion of colistin resistance within diverse genus and species groups and the higher incidence observed among carbapenemase-producing MDR pathogens are concerning.
Colistin-Resistant Acinetobacter baumannii Clinical Strains with Deficient Biofilm Formation
Authors: Dafopoulou Konstantina , Xavier Basil Britto , Hotterbeekx An , Janssens Lore , Lammens Christine , Dé Emmanuelle , Goossens Herman , Tsakris Athanasios , Malhotra-Kumar Surbhi , Pournaras Spyros 
Published: December 2015

ABSTRACT

In two pairs of clinical colistin-susceptible/colistin-resistant (Cst
s
/Cst
r
)
Acinetobacter baumannii
strains, the Cst
r
strains showed significantly decreased biofilm formation in static and dynamic assays (
P
< 0.001) and lower relative fitness (
P
< 0.05) compared with those of the Cst
s
counterparts. The whole-genome sequencing comparison of strain pairs identified a mutation converting a stop codon to lysine (*241K) in LpsB (involved in lipopolysaccharide [LPS] synthesis) in one Cst
r
strain and a frameshift mutation in CarO and the loss of a 47,969-bp element containing multiple genes associated with biofilm production in the other.
Effects of Stress, Reactive Oxygen Species, and the SOS Response on
De Novo
Acquisition of Antibiotic Resistance in Escherichia coli
Authors: Händel Nadine , Hoeksema Marloes , Freijo Mata Marina , Brul Stanley , ter Kuile Benno H. 
Published: December 2015

ABSTRACT

Strategies to prevent the development of antibiotic resistance in bacteria are needed to reduce the threat of infectious diseases to human health. The
de novo
acquisition of resistance due to mutations and/or phenotypic adaptation occurs rapidly as a result of interactions of gene expression and mutations (N. Handel, J. M. Schuurmans, Y. Feng, S. Brul, and B. H. Ter Kuile, Antimicrob Agents Chemother 58:4371–4379, 2014,
http://dx.doi.org/10.1128/AAC.02892-14
). In this study, the contribution of several individual genes to the
de novo
acquisition of antibiotic resistance in
Escherichia coli
was investigated using mutants with deletions of genes known to be involved in antibiotic resistance. The results indicate that
recA
, vital for the SOS response, plays a crucial role in the development of antibiotic resistance. Likewise, deletion of global transcriptional regulators, such as
gadE
or
soxS
, involved in pH homeostasis and superoxide removal, respectively, can slow the acquisition of resistance to a degree depending on the antibiotic. Deletion of the transcriptional regulator
soxS
, involved in superoxide removal, slowed the acquisition of resistance to enrofloxacin. Acquisition of resistance occurred at a lower rate in the presence of a second stress factor, such as a lowered pH or increased salt concentration, than in the presence of optimal growth conditions. The overall outcome suggests that a central cellular mechanism is crucial for the development of resistance and that genes involved in the regulation of transcription play an essential role. The actual cellular response, however, depends on the class of antibiotic in combination with environmental conditions.
Tailoring a Combination Preerythrocytic Malaria Vaccine
Authors: Bauza Karolis , Atcheson Erwan , Malinauskas Tomas , Blagborough Andrew M. , Reyes-Sandoval Arturo 
Published: December 2015

ABSTRACTThe leading malaria vaccine candidate, RTS,S, based on thePlasmodium falciparumcircumsporozoite protein (CSP), will likely be the first publicly adopted malaria vaccine. However, this and other subunit vaccines, such as virus-vectored thrombospondin-related adhesive protein (TRAP), provide only intermediate to low levels of protection. In this study, thePlasmodium bergheihomologues of antigens CSP and TRAP are combined. TRAP is delivered using adenovirus- and vaccinia virus-based vectors in a prime-boost regime. Initially, CSP is also delivered using these viral vectors; however, a reduction of anti-CSP antibodies is seen when combined with virus-vectored TRAP, and the combination is no more protective than either subunit vaccine alone. Using an adenovirus-CSP prime, protein-CSP boost regime, however, increases anti-CSP antibody titers by an order of magnitude, which is maintained when combined with virus-vectored TRAP. This combination regime using protein CSP provided 100% protection in C57BL/6 mice compared to no protection using virus-vectored TRAP alone and 40% protection using adenovirus-CSP prime and protein-CSP boost alone. This suggests that a combination of CSP and TRAP subunit vaccines could enhance protection against malaria.
The C-Type Lectin Receptor MCL Mediates Vaccine-Induced Immunity against Infection with Blastomyces dermatitidis
Authors: Wang Huafeng , Li Mengyi , Lerksuthirat Tassanee , Klein Bruce , Wüthrich Marcel 
Published: December 2015

ABSTRACT

C-type lectin receptors (CLRs) are essential in shaping the immune response to fungal pathogens. Vaccine-induced resistance requires Dectin-2 to promote differentiation of antifungal Th1 and Th17 cells. Since Dectin-2 and MCL heterodimerize and both CLRs use FcRγ as the signaling adaptor, we investigated the role of MCL in vaccine immunity to the fungal pathogen
Blastomyces dermatitidis
. MCL
−/−
mice showed impaired vaccine resistance against
B. dermatitidis
infection compared to that of wild-type animals. The lack of resistance correlated with the reduced recruitment of Th17 cells to the lung upon recall following experimental challenge and impaired interleukin-17 (IL-17) production by vaccine antigen-stimulated splenocytes
in vitro
. Soluble MCL fusion protein recognized and bound a water-soluble ligand from the cell wall of vaccine yeast, but the addition of soluble Dectin-2 fusion protein did not augment ligand recognition by MCL. Taken together, our data indicate that MCL regulates the development of vaccine-induced Th17 cells and protective immunity against lethal experimental infection with
B. dermatitidis
.
Stability of the GraA Antitoxin Depends on Growth Phase, ATP Level, and Global Regulator MexT
Authors: Tamman Hedvig , Ainelo Andres , Tagel Mari , Hõrak Rita 
Published: December 2015

ABSTRACTBacterial type II toxin-antitoxin systems consist of a potentially poisonous toxin and an antitoxin that inactivates the toxic protein by binding to it. Most of the toxins regulate stress survival, but their activation depends on the stability of the antitoxin that has to be degraded in order for the toxin to be able to attack its cellular targets. The degradation of antitoxins is usually rapid and carried out by ATP-dependent protease Lon or Clp, which is activated under stress conditions. ThegraTAsystem ofPseudomonas putidaencodes the toxin GraT, which can affect the growth rate and stress tolerance of bacteria but is under most conditions inactivated by the unusually stable antitoxin GraA. Here, we aimed to describe the stability features of the antitoxin GraA by analyzing its degradation rate in total cell lysates ofP. putida. We show that the degradation rate of GraA depends on the growth phase of bacteria being fastest in the transition from exponential to stationary phase. In accordance with this, higher ATP levels were shown to stabilize GraA. Differently from other antitoxins, the main cellular proteases Lon and Clp are not involved in GraA stability. Instead, GraA seems to be degraded through a unique pathway involving an endoprotease that cleaves the antitoxin into two unequal parts. We also identified the global transcriptional regulator MexT as a factor for destabilization of GraA, which indicates that the degradation of GraA may be induced by conditions similar to those that activate MexT.IMPORTANCEToxin-antitoxin (TA) modules are widespread in bacterial chromosomes and have important roles in stress tolerance. As activation of a type II toxin is triggered by proteolytic degradation of the antitoxin, knowledge about the regulation of the antitoxin stability is critical for understanding the activation of a particular TA module. Here, we report on the unusual degradation pathway of the antitoxin GraA of the recently characterized GraTA system. While GraA is uncommonly stable in the exponential and late-stationary phases, its degradation increases in the transition phase. The degradation pathway of GraA involves neither Lon nor Clp, which usually targets antitoxins, but rather an unknown endoprotease and the global regulator MexT, suggesting a new type of regulation of antitoxin stability.
Altering the Structure of Carbohydrate Storage Granules in the Cyanobacterium Synechocystis sp. Strain PCC 6803 through Branching-Enzyme Truncations
Authors: Welkie David G. , Lee Byung-Hoo , Sherman Louis A. 
Published: December 2015

ABSTRACT

Carbohydrate storage is an important element of metabolism in cyanobacteria and in the chloroplasts of plants. Understanding how to manipulate the metabolism and storage of carbohydrate is also an important factor toward harnessing cyanobacteria for energy production. While most cyanobacteria produce glycogen, some have been found to accumulate polysaccharides in the form of water-insoluble α-glucan similar to amylopectin. Notably, this alternative form, termed “semi-amylopectin,” forms in cyanobacterial species harboring three branching-enzyme (BE) homologs, designated BE1, BE2, and BE3. In this study, mutagenesis of the branching genes found in
Synechocystis
sp. strain PCC 6803 was performed in order to characterize their possible impact on polysaccharide storage granule morphology. N-terminal truncations were made to the native BE gene of
Synechocystis
sp. PCC 6803. In addition, one of the two native debranching enzyme genes was replaced with a heterologous debranching enzyme gene from a semi-amylopectin-forming strain. Growth and glycogen content of mutant strains did not significantly differ from those of the wild type, and ultrastructure analysis revealed only slight changes to granule morphology. However, analysis of chain length distribution by anion-exchange chromatography revealed modest changes to the branched-chain length profile. The resulting glycogen shared structure characteristics similar to that of granules isolated from semi-amylopectin-producing strains.

IMPORTANCE
This study is the first to investigate the impact of branching-enzyme truncations on the structure of storage carbohydrates in cyanobacteria. The results of this study are an important contribution toward understanding the relationship between the enzymatic repertoire of a cyanobacterial species and the morphology of its storage carbohydrates.
Variation in paediatric hospital antibiotic guidelines in Europe
Authors: Spyridis N , Syridou G , Goossens H , Versporten A , Kopsidas J , Kourlaba G , Bielicki J , Drapier N , Zaoutis T , Tsolia M , Sharland M 
Published: December 2015

ObjectiveTo assess the availability and source of guidelines for common infections in European paediatric hospitals and determine their content and characteristics.DesignParticipating hospitals completed an online questionnaire on the availability and characteristics of antibiotic prescribing guidelines and on empirical antibiotic treatment including duration of therapy for 5 common infection syndromes: respiratory tract, urinary tract, skin and soft tissue, osteoarticular and sepsis in neonates and children.Results84 hospitals from 19 European countries participated in the survey of which 74 confirmed the existence of guidelines. Complete guidelines (existing guidelines for all requested infection syndromes) were reported by 20% of hospitals and the majority (71%) used a range of different sources. Guidelines most commonly available were those for urinary tract infection (UTI) (74%), neonatal sepsis (71%) and sepsis in children (65%). Penicillin and amoxicillin were the antibiotics most commonly recommended for respiratory tract infections (RTIs) (up to 76%), cephalosporin for UTI (up to 50%) and for skin and soft tissue infection (SSTI) and bone infection (20% and 30%, respectively). Antistaphylococcal penicillins were recommended for SSTIs and bone infections in 43% and 36%, respectively. Recommendations for neonatal sepsis included 20 different antibiotic combinations. Duration of therapy guidelines was mostly available for RTI and UTI (82%). A third of hospitals with guidelines for sepsis provided recommendations for length of therapy.ConclusionsComprehensive antibiotic guideline recommendations are generally lacking from European paediatric hospitals. We documented multiple antibiotics and combinations for most infections. Considerable improvement in the quality of guidelines and their evidence base is required, linking empirical therapy to resistance rates.
PERSONALIZATION OF 6-MERCAPTOPURINE THERAPY FOR CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Milošević Goran , Dokmanović Lidija , Krstovski Nada , Lazić Jelena , Rodić Predrag , Pavlović Sonja , Zukić Branka , Kotur Nikola , Janić Dragana 
Published: December 2015

IntroductionTreatment of acute lymphoblastic leukemia (ALL) in children has been significantly improved over past few decades. Optimal use of known antileukemic drugs has lead to four-fold increase of overall survival. Nevertheless, therapy failure occurs in 15–20% of patients. Individualized use of cytostatic drugs can help us reducing toxicity-related deaths and improve therapy outcome.Materials and methodsWe studied multidrug resistance protein 4 gene (ABCC4) and inosin triphosphate pyrophosphatase (ITPA) gene polymorphisms to assess their influence on occurrence and intensity of 6-MP toxicity during maintenance phase of ALL treatment in children as well as on treatment outcome.ResultsThiopurine S-methyltransferase (TPMT) genotype was known for all patients before start of therapy and doses were adjusted accordingly. Five patients (7%) were carriers of ITPAc.94C>A genotype. Heterozygote and homozygote carriers of variant alleles for ABCC4 rs9516519 T>G, genotype were represented in 35% and 4% of our patients, respectively. We did not show correlation of variant alleles with increased number of off-therapy weeks neither with number of episodes of leukopenia. Cross-validated AUC for each of genetic markers individually showed low predictive power (cross-validated AUC around 0.5) for predicting toxicity. However, combination of two genetic markers and known TPMT gentotype improved the predictability (cross-validated AUC was 0.65).ConclusionsOur results did not show correlation with toxicity using individual genetic markers. However, in the settings of known TPMT genotype, we showed the potential of using all three genetic markers (including TPMT) in predicting who might be in danger of having increased toxicity.
EUROPEAN PAEDIATRIC ONCOLOGY OFF-PATENT MEDICINES CONSORTIUM (EPOC): A PHARMACOKINETIC STUDY OF DOXORUBICIN IN CHILDREN WITH CANCER
Authors: Krischke Miriam , Boddy Alan V , Hempel Georg , Völler Swantje , André Nicolas , D'Incalci Mauricio 
Published: December 2015

BackgroundDoxorubicin is a key component of a number of treatment regimens used in paediatric oncology. The pharmacology data on which current dosing regimens are based are very limited.MethodsWe conducted a multicentre, multinational pharmacokinetic study investigating age-dependency in the clearance of doxorubicin in children with solid tumours and leukaemia. Blood samples for measurement of doxorubicin and its metabolite doxorubicinol were collected after 2 administrations, with 5 samples collected in children 3 yrs. A population pharmacokinetic approach was used for analysis, including pharmacogenetic covariates. NT-proBNP and cardiac troponin T were measured to evaluate their role as early indicators of cardiotoxicity.Results101 children could be recruited including 27 patients less than 3 years and among those 5 infants younger than 1 year. Overall, the patient acceptance of the trial was very good.Age dependence of doxorubicin clearance was demonstrated, with children less than 3 years having a lower clearance (21.1±5.8 l/h/m2) than older children (26.6±6.7 l/h/m2) (p=0.0004), after correcting for body weight. Pharmacogenetic variants, including those in transporters and drug metabolizing enzymes, had little influence on pharmacokinetic parameters.Natriuretic peptides plasma levels increased significantly shortly after doxorubicin administration, whereas cardiac troponin levels increased only with the administered cumulative anthracycline dose. Only limited correlation could be observed between their blood levels and doxorubicin pharmacokinetics.ConclusionThe paediatric need concerning missing PK-data could be addressed with limited burden for the patients. Empirically used dose adaptations for infants were found to be justified based on our PK analyses.