bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preschoolers' Mind‐related Comments During Collaborative Problem‐solving: Parental Contributions and Developmental Outcomes
Authors: Lundy Brenda L. , Fyfe Gracee 
Published: December 2015

AbstractPreschool children's mind‐related comments were analyzed during collaborative problem‐solving interactions with mothers and fathers, and in relation to parental mind‐mindedness (MM) and children's concurrent theory of mind (ToM). Seventy‐two parents (36 fathers, 36 mothers) and their four‐year‐olds participated. Parents' comments to encourage independent thinking and children's own mind‐related comments were expected to mediate, in serial, the relationship between parental MM and children's ToM. The proposed model of mediation received empirical confirmation. In addition, mothers and fathers were found to perform similarly on two measures of MM and in their usage of autonomy promoting and control comments. Finally, no differences were found in the frequency of children's mind‐related comments during interactions with fathers and mothers.
Probabilistic soil mapping by Bayesian inference to assess suitability for derocking in northwest Syria
Authors: Hawinkel P. , De Pauw E. , Deckers J. 
Published: December 2015

AbstractLand reclamation by rock removal has wide potential in areas with shallow or rocky soils. In northwest Syria, this practice is hindered in its implementation by a lack of physical soil suitability data, principally soil rockiness and soil depth to hard rock. These soil properties were surveyed in a limited study area, resulting in a hard‐boundary thematic soil map (64–94% accuracy per property). Bayesian inference is proposed as a low‐cost upscaling method that yields a set of pixel‐based probability maps, providing improved input for spatial decision support models. Whereas the achieved spatial upscaling (from 2510 to 19 100 ha) outweighed the decrease in overall accuracy (down to 26–57%), probability maps require dedicated validation and manipulation procedures. This research contributes to methods for the creation, validation and interpretation of probabilistic soil property maps for quantitative land evaluation. First, we evaluated three postprocessing and validation methods for probabilistic soil property maps, identifying the use of ‘prediction rates’ as the best approach in a spatial planning context. Next, we demonstrated how the maps can support decision‐making for land management activities by simulating the expected losses and gains from interventions, in a decision‐theoretic approach. Based on the simulations, the investments in large‐scale derocking projects in northwest Syria will pay off in terms of increased agricultural productivity in less than 10 years.
Interpopulation hybridization generates meiotically stable rDNA epigenetic variants in allotetraploid Tragopogon mirus
Authors: Matyášek Roman , Dobešová Eva , Húska Dalibor , Ježková Ivana , Soltis Pamela S. , Soltis Douglas E. , Kovařík Aleš 
Published: December 2015

SummaryUniparental silencing of 35S rRNA genes (rDNA), known as nucleolar dominance (ND), is common in interspecific hybrids. Allotetraploid Tragopogon mirus composed of Tragopogon dubius (d) and Tragopogon porrifolius (p) genomes shows highly variable ND. To examine the molecular basis of such variation, we studied the genetic and epigenetic features of rDNA homeologs in several lines derived from recently and independently formed natural populations. Inbred lines derived from T. mirus with a dominant d‐rDNA homeolog transmitted this expression pattern over generations, which may explain why it is prevalent among natural populations. In contrast, lines derived from the p‐rDNA dominant progenitor were meiotically unstable, frequently switching to co‐dominance. Interpopulation crosses between progenitors displaying reciprocal ND resulted in d‐rDNA dominance, indicating immediate suppression of p‐homeologs in F1 hybrids. Original p‐rDNA dominance was not restored in later generations, even in those segregants that inherited the corresponding parental rDNA genotype, thus indicating the generation of additional p‐rDNA and d‐rDNA epigenetic variants. Despite preserved intergenic spacer (IGS) structure, they showed altered cytosine methylation and chromatin condensation patterns, and a correlation between expression, hypomethylation of RNA Pol I promoters and chromatin decondensation was apparent. Reversion of such epigenetic variants occurred rarely, resulting in co‐dominance maintained in individuals with distinct genotypes. Generally, interpopulation crosses may generate epialleles that are not present in natural populations, underlying epigenetic dynamics in young allopolyploids. We hypothesize that highly expressed variants with distinct IGS features may induce heritable epigenetic reprogramming of the partner rDNA arrays, harmonizing the expression of thousands of genes in allopolyploids.
Shape matters: the effect of red blood cell shape on perfusion of an artificial microvascular network
Authors: Piety Nathaniel Z. , Reinhart Walter H. , Pourreau Patrick H. , Abidi Rajaa , Shevkoplyas Sergey S. 
Published: December 2015

BACKGROUNDThe shape of human red blood cells (RBCs) deteriorates progressively throughout hypothermic storage, with echinocytosis being the most prevalent pathway of this morphologic lesion. As a result, each unit of stored blood contains a heterogeneous mixture of cells in various stages of echinocytosis and normal discocytes. Here we studied how the change in shape of RBCs following along the path of the echinocytic transformation affects perfusion of an artificial microvascular network (AMVN).STUDY DESIGN AND METHODSBlood samples were obtained from healthy consenting volunteers. RBCs were leukoreduced, resuspended in saline, and treated with various concentrations of sodium salicylate to induce shape changes approximating the stages of echinocytosis experienced by RBCs during hypothermic storage (e.g., discocyte, echinocyte I, echinocyte II, echinocyte III, spheroechinocyte, and spherocyte). The AMVN perfusion rate was measured for 40% hematocrit suspensions of RBCs with different shapes.RESULTSThe AMVN perfusion rates for RBCs with discocyte and echinocyte I shapes were similar, but there was a significant decline in the AMVN perfusion rate between RBCs with shapes approximating each subsequent stage of echinocytosis. The difference in AMVN perfusion between discocytes and spherocytes (the last stage of the echinocytic transformation) was 34%.CONCLUSIONThe change in shape of RBCs from normal discocytes progressively through various stages of echinocytosis to spherocytes produced a substantial decline in the ability of these cells to perfuse an AMVN. Echinocytosis induced by hypothermic storage could therefore be responsible for a similarly substantial impairment of deformability previously observed for stored RBCs.
Antibiofilm Activity of Electrical Current in a Catheter Model
Authors: Voegele Paul , Badiola Jon , Schmidt-Malan Suzannah M. , Karau Melissa J. , Greenwood-Quaintance Kerryl E. , Mandrekar Jayawant N. , Patel Robin 
Published: December 2015

ABSTRACT

Catheter-associated infections are difficult to treat with available antimicrobial agents because of their biofilm etiology. We examined the effect of low-amperage direct electrical current (DC) exposure on established bacterial and fungal biofilms in a novel experimental
in vitro
catheter model.
Staphylococcus epidermidis
,
Staphylococcus aureus
,
Escherichia coli
,
Pseudomonas aeruginosa
, and
Candida parapsilosis
biofilms were grown on the inside surfaces of polyvinyl chloride (PVC) catheters, after which 0, 100, 200, or 500 μA of DC was delivered via intraluminally placed platinum electrodes. Catheter biofilms and intraluminal fluid were quantitatively cultured after 24 h and 4 days of DC exposure. Time- and dose-dependent biofilm killing was observed with all amperages and durations of DC administration. Twenty-four hours of 500 μA of DC sterilized the intraluminal fluid for all bacterial species studied; no viable bacteria were detected after treatment of
S. epidermidis
and
S. aureus
biofilms with 500 μA of DC for 4 days.
Mutations That Enhance the Ciprofloxacin Resistance of Escherichia coli with
qnrA1
Authors: Vinué Laura , Corcoran Marian A. , Hooper David C. , Jacoby George A. 
Published: December 2015

ABSTRACT

Plasmid-mediated
qnr
genes provide only a modest decrease in quinolone susceptibility but facilitate the selection of higher-level resistance. In
Escherichia coli
strain J53 without
qnr
, ciprofloxacin resistance often involves mutations in the GyrA subunit of DNA gyrase. Mutations in
gyrA
were absent, however, when 43 mutants with decreased ciprofloxacin susceptibility were selected from J53(pMG252) with
qnrA1
. Instead, in 13 mutants, individual and whole-genome sequencing identified mutations in
marR
and
soxR
associated with increased expression of
marA
and
soxS
and, through them, increased expression of the AcrAB pump, which effluxes quinolones. Nine mutants had increased expression of the MdtE efflux pump, and six demonstrated increased expression of the
ydhE
pump gene. Many efflux mutants also had increased resistance to novobiocin, another pump substrate, but other mutants were novobiocin hypersusceptible. Mutations in
rfaD
and
rfaE
in the pathway for inner core lipopolysaccharide (LPS) biosynthesis were identified in five such strains. Many of the pump and LPS mutants had decreased expression of OmpF, the major porin channel for ciprofloxacin entry. Three mutants had increased expression of
qnrA
that persisted when pMG252 from these strains was outcrossed.
gyrA
mutations were also rare when mutants with decreased ciprofloxacin susceptibility were selected from
E. coli
J53 with
aac(6
′
)-Ib-cr
or
qepA
. We suggest that multiple genes conferring low-level resistance contribute to enhanced ciprofloxacin resistance selected from an
E. coli
strain carrying
qnrA1
,
aac(6
′
)-Ib-cr
, or
qepA
because these determinants decrease the effective ciprofloxacin concentration and allow more common but lower-resistance mutations than those in
gyrA
to predominate.
Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs
Authors: Fernandes Chantal , Prados-Rosales Rafael , Silva Branca M. A. , Nakouzi-Naranjo Antonio , Zuzarte Mónica , Chatterjee Subhasish , Stark Ruth E. , Casadevall Arturo , Gonçalves Teresa 
Published: December 2015

ABSTRACT

The importance of
Alternaria
species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on
Alternaria infectoria
, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by
A. infectoria
, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that
A. infectoria
increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that
A. infectoria
activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized
A. infectoria
cell walls. In summary,
A. infectoria
synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis.
Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 2
Authors: Drusano G. L. , Hope William , MacGowan Alasdair , Louie Arnold 
Published: December 2015

ABSTRACT

We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens like
Pseudomonas aeruginosa
,
Acinetobacter
spp., and multidrug-resistant (MDR)
Enterobacteriaceae
. These lessons need to be applied to our old drugs as well to preserve them and to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.
Membrane-Bound PenA β-Lactamase of Burkholderia pseudomallei
Authors: Randall Linnell B. , Dobos Karen , Papp-Wallace Krisztina M. , Bonomo Robert A. , Schweizer Herbert P. 
Published: December 2015

ABSTRACT

Burkholderia pseudomallei
is the etiologic agent of melioidosis, a difficult-to-treat disease with diverse clinical manifestations. β-Lactam antibiotics such as ceftazidime are crucial to the success of melioidosis therapy. Ceftazidime-resistant clinical isolates have been described, and the most common mechanism is point mutations affecting expression or critical amino acid residues of the chromosomally encoded class A PenA β-lactamase. We previously showed that PenA was exported via the twin arginine translocase system and associated with the spheroplast fraction. We now show that PenA is a membrane-bound lipoprotein. The protein and accompanying β-lactamase activity are found in the membrane fraction and can be extracted with Triton X-114. Treatment with globomycin of
B. pseudomallei
cells expressing PenA results in accumulation of the prolipoprotein. Mass spectrometric analysis of extracted membrane proteins reveals a protein peak whose mass is consistent with a triacylated PenA protein. Mutation of a crucial lipobox cysteine at position 23 to a serine residue results in loss of β-lactamase activity and absence of detectable PenA
C23S
protein. A concomitant isoleucine-to-alanine change at position 20 in the signal peptide processing site in the PenA
C23S
mutant results in a nonlipidated protein (PenA
I20A C23S
) that is processed by signal peptidase I and exhibits β-lactamase activity. The resistance profile of a
B. pseudomallei
strain expressing this protein is indistinguishable from the profile of the isogenic strain expressing wild-type PenA. The data show that PenA membrane association is not required for resistance and must serve another purpose.
Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy
Authors: Lhomme Sebastien , Kamar Nassim , Nicot Florence , Ducos Jacques , Bismuth Michael , Garrigue Valerie , Petitjean-Lecherbonnier Joelle , Ollivier Isabelle , Alessandri-Gradt Elodie , Goria Odile , Barth Heidi , Perrin Peggy , Saune Karine , Dubois Martine , Carcenac Romain , Lefebvre Caroline , Jeanne Nicolas , Abravanel Florence , Izopet Jacques 
Published: December 2015

ABSTRACT

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (
P
= 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.
Differential Mechanisms of Tenofovir and Tenofovir Disoproxil Fumarate Cellular Transport and Implications for Topical Preexposure Prophylaxis
Authors: Taneva Ekaterina , Crooker Kerry , Park Sung Hyun , Su Jonathan T. , Ott Adina , Cheshenko Natalia , Szleifer Igal , Kiser Patrick F. , Frank Bruce , Mesquita Pedro M. M. , Herold Betsy C. 
Published: December 2015

ABSTRACTIntravaginal rings releasing tenofovir (TFV) or its prodrug, tenofovir disoproxil fumarate (TDF), are being evaluated for HIV and herpes simplex virus (HSV) prevention. The current studies were designed to determine the mechanisms of drug accumulation in human vaginal and immune cells. The exposure of vaginal epithelial or T cells to equimolar concentrations of radiolabeled TDF resulted in over 10-fold higher intracellular drug levels than exposure to TFV. Permeability studies demonstrated that TDF, but not TFV, entered cells by passive diffusion. TDF uptake was energy independent but its accumulation followed nonlinear kinetics, and excess unlabeled TDF inhibited radiolabeled TDF uptake in competition studies. The carboxylesterase inhibitor bis-nitrophenyl phosphate reduced TDF uptake, suggesting saturability of intracellular carboxylesterases. In contrast, although TFV uptake was energy dependent, no competition between unlabeled and radiolabeled TFV was observed, and the previously identified transporters, organic anion transporters (OATs) 1 and 3, were not expressed in human vaginal or T cells. The intracellular accumulation of TFV was reduced by the addition of endocytosis inhibitors, and this resulted in the loss of TFV antiviral activity. Kinetics of drug transport and metabolism were monitored by quantifying the parent drugs and their metabolites by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Results were consistent with the identified mechanisms of transport, and the exposure of vaginal epithelial cells to equimolar concentrations of TDF compared to TFV resulted in ∼40-fold higher levels of the active metabolite, tenofovir diphosphate. Together, these findings indicate that substantially lower concentrations of TDF than TFV are needed to protect cells from HIV and HSV-2.
Evaluation of Daptomycin Exposure and Efficacy and Safety Endpoints To Support Risk-versus-Benefit Considerations
Authors: Bhavnani Sujata M. , Ambrose Paul G. , Hammel Jeffrey P. , Rubino Christopher M. , Drusano George L. 
Published: December 2015

ABSTRACT

The choice of an antimicrobial agent must balance optimization of efficacy endpoints with the minimization of safety events. The risk versus benefit of daptomycin for patients with
Staphylococcus aureus
bacteremia with or without infective endocarditis receiving daptomycin at 6, 8, and 10 mg/kg of body weight/day was assessed. The relationships between the area under the concentration-time curve over 24 h (AUC)/MIC ratio and both clinical response and time to decreased susceptibility were evaluated using data from patients with such infections who received daptomycin at 6 mg/kg/day. Using these relationships, plus the previously identified relationship between the minimum concentration and an elevation in the creatine phosphokinase (CPK) concentration (CPK elevation) (S. M. Bhavnani, C. M. Rubino, P. G. Ambrose, and G. L. Drusano, Clin Infect Dis 50:1568–1574, 2010) and Monte Carlo simulation, the probability of each outcome by MIC for daptomycin at 6, 8, and 10 mg/kg/day was calculated. The function for exposure-response relationships for clinical response (
P
= 0.06) and time to decreased susceptibility (
P
= 0.01) resembled U and inverted U shapes, respectively. Multivariable analyses demonstrated AUC/MIC ratio, creatinine clearance, albumin concentration, and disease category to be predictors of clinical response. The results of simulations failed to demonstrate large improvements in the probabilities of clinical success among cohorts of simulated patients defined by the above-described predictive factors or the probability of decreased susceptibility at 30 days when the daptomycin dose was increased from 6 to 10 mg/kg/day. The probability of CPK elevation increased from 0.073 to 0.156 over this dose range. These data can be used to inform risk-versus-benefit decisions for daptomycin dose selection in patients with
S. aureus
bacteremia with or without infective endocarditis. The risk of CPK elevation, which is reversible, should be weighed in the context of the mortality and severe morbidity associated with these types of serious staphylococcal infections.
Flocculation-Related Gene Identification by Whole-Genome Sequencing of Thauera aminoaromatica MZ1T Floc-Defective Mutants
Authors: Prombutara P. , Allen M. S. 
Published: December 2015

ABSTRACT

Thauera aminoaromatica
MZ1T, a floc-forming bacterium isolated from an industrial activated-sludge wastewater treatment plant, overproduces exopolysaccharide (EPS), leading to viscous bulking. This phenomenon results in poor sludge settling and dewatering during the clarification process. To identify genes responsible for bacterial flocculation, a whole-genome phenotypic-sequencing technique was applied. Genomic DNA of MZ1T flocculation-deficient mutants was subjected to massively parallel sequencing. The resultant high-quality reads were assembled and compared to the reference genome of the wild type (WT). We identified nine nonsynonymous mutations and one nonsense mutation putatively involved in EPS biosynthesis. Complementation of the nonsense mutation located in an EPS deacetylase gene restored the flocculating phenotype. The Fourier transform infrared (FTIR) spectra of EPS isolated from the wild type showed a reduced C=O peak of the
N
-acetyl group at 1,665 cm
−1
compared to the spectra of MZ1T floc-deficient mutant EPS, suggesting that the WT EPS was partially deacetylated. Gene expression analysis also demonstrated that the putative deacetylase gene transcript increased before flocculation occurred. These data suggest that targeting deacetylation processes via direct chemical modification of EPS or enzyme inhibition may prove useful in combating viscous bulking in this and related bacteria.