bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting the virulence of Ralstonia solanacearum and its colonization on tobacco roots
Authors: Li X. , Liu Y. , Cai L. , Zhang H. , Shi J. , Yuan Y. 
Published: January 2017

Tobacco bacterial wilt caused by Ralstonia solanacearum is a serious disease affecting tobacco cultivation in southwest China. The response surface methodology was employed to evaluate the optimal conditions of tobacco bacterial wilt, and green fluorescent protein gene (gfp) labelling was applied to monitor the location and survival dynamics of R. solanacearum (Rs::gfp) on tobacco roots and in soil under these optimal conditions. The results showed that the highest wilt incidence was 91.13%, which occurred when the population reached 6.6 × 106 CFU/g soil, the temperature was 30.55 °C, and the humidity was >81.42%. The Rs::gfp densely colonized the root tips and root hairs, and cells of Rs::gfp were observed intermittently in the elongation zone or at the point of the emerging lateral roots. The Rs::gfp number in the rhizosphere soil was 10.75‐, 73.13‐ and 74.86‐times higher than that in the bulk soil at 10, 15 and 20 days after transplantation, respectively. Increased colonization by Rs::gfp was related to the population of the pathogen, the environmental temperature and the humidity in the soil. These three conditions determined whether R. solanacearum would induce tobacco wilt. This is the first study to investigate factors affecting the virulence of a tobacco wilt bacterial pathogen, which is important for conducting field diagnosis and biocontrol of tobacco bacterial wilt.
The elicitation of steady‐state visual evoked potentials during sleep
Authors: Norton James J. S. , Umunna Stephen , Bretl Timothy 
Published: January 2017

AbstractThis study confirmed the hypothesis that it is possible to elicit SSVEPs through closed eyelids during NREM sleep. To test this hypothesis, SSVEP amplitudes were measured in eight subjects across two conditions of stimulation (stimulation on and stimulation off) and three brain states (waking, light sleep, and deep sleep). Results showed a significant interaction between stimulation and brain state. In particular, EEG activity at the frequency of stimulation was higher during both light sleep and deep sleep in the stimulation on condition than in the stimulation off condition. The fact that it is possible to elicit SSVEPs during sleep may provide a new way to study how SSVEPs are generated in the brain—one that might help resolve open questions such as identifying the SSVEP activation sequence or deciding if SSVEPs derive from evoked or oscillatory neural processes.
Legal Principles in Antitrust Enforcement
Authors: Houba Harold , Motchenkova Evgenia , Wen Quan 
Published: January 2017

AbstractWe study antitrust enforcement that aims to channel price‐fixing incentives of cartels through setting fine schedules and detection levels. Fines obey legal principles, such as the punishment should fit the crime, proportionality, bankruptcy considerations, and minimum fines. Bankruptcy considerations limit maximum fines, ensure abnormal cartel profits, and impose a challenge for optimal antitrust enforcement. We derive the fine schedule and detection level that are constrained‐optimal under legal principles and sustainability of cartel prices. This fine schedule lies below the maximum fine, makes collusion on lower prices more attractive than on higher prices, and, hence, relates to the body of literature on marginal deterrence.
How Effective Are Non‐Monetary Instruments for Safe Driving? Panel Data Evidence on the Effect of the Demerit Point System in Denmark
Authors: Abay Kibrom A. 
Published: January 2017

AbstractUsing unusually rich longitudinal data on traffic offenses, this paper exploits a reform that introduced a point‐recording scheme in Denmark to estimate the behavioral responses of drivers to a non‐monetary penalty based on demerit points. We find that drivers exhibited substantial behavioral responses to each demerit point assigned to their driving licenses. We also find that drivers’ efforts, and hence responses, increased with the number of demerit points they accumulated. Depending on the number of demerit points accumulated, drivers with one or more demerit points reduced their frequency of traffic offenses by 9–34 percent.
Marriage Delay, Time to Play? Marital Horizons and Hooking Up in College
Authors: Allison Rachel , Risman Barbara J. 
Published: January 2017

Previous research suggests that an increasing age at first marriage has contributed to the prevalence of sexual hookups on U.S. college campuses. In this article, we use life course and marital horizons theories to analyze the influence of ideal age at first marriage on hooking up among unmarried heterosexual college students. Analyses of the Online College Social Life Survey (N = 17,981) show a positive association between ideal age at first marriage and hookups for most students, but not for students whose mothers have no post‐secondary education, Asian men, Asian women, and Latina women. Variation in ideal marriage timing does not account for gender, racial/ethnic, and class gaps in hookup participation. Results are discussed with reference to the role of sexuality in processes of stratification throughout young adulthood.
Pseudozyma and other non‐Candida opportunistic yeast bloodstream infections in a large stem cell transplant center
Authors: Pande Anupam , Non Lemuel R. , Romee Rizwan , Santos Carlos A. Q. 
Published: January 2017

AbstractNon‐Candida opportunistic yeasts are emerging causes of bloodstream infection (BSI) in immunocompromised hosts. However, their clinical presentation, management, and outcomes in stem cell transplant (SCT) recipients are not well described. We report the first case to our knowledge of Pseudozyma BSI in a SCT recipient. He had evidence of cutaneous involvement, which has not been previously described in the literature. He became infected while neutropenic and receiving empiric micafungin, which is notable because Pseudozyma is reported to be resistant to echinocandins. He was successfully treated with the sequential use of liposomal amphotericin B and voriconazole. A review of the literature revealed nine reported instances of Pseudozyma fungemia. We performed a retrospective review of 3557 SCT recipients at our institution from January 2000 to June 2015 and identified four additional cases of non‐Candida yeast BSIs. These include two with Cryptococcus, one with Trichosporon, and one with Saccharomyces. Pseudozyma and other non‐Candida yeasts are emerging pathogens that can cause severe and disseminated infections in SCT recipients and other immunocompromised hosts. Clinicians should have a high degree of suspicion for echinocandin‐resistant yeasts, if patients develop breakthrough yeast BSIs while receiving echinocandin therapy.
Validation of a smartphone‐based point‐of‐care hemoglobin assay for use in dogs
Authors: Farrell Kate S. , Chapman Phillip L. , Sullivan Lauren A. 
Published: January 2017

AbstractObjectiveTo validate a smartphone‐based spectrophotometric assay for point‐of‐care (POC) measurement of hemoglobin (Hgb) concentration against the standard measurement method in dogs without increases in serum lipemia, hemolysis, or bilirubin.DesignProspective observational study.SettingUniversity teaching hospital.AnimalsOne hundred thirty‐nine dogs that had a CBC and corresponding biochemical profile submitted to the clinical pathology laboratory.InterventionsNone.Measurements and Main ResultsBlood tubes submitted for CBC were collected for hemoglobin (Hgb) measurements performed on a POC smartphone device. Each whole blood sample was run on the smartphone in duplicate using 2 strips, for a total of 4 POC Hgb readings per dog. Data collected for each dog included CBC Hgb value, 4 POC Hgb values, and select biochemistry values (bilirubin, lipemia, hemolysis, icterus). A calibration equation was estimated using a weighted linear regression: estimated CBC = (avgPOC–0.4871)/1.0015. For each dog, the percent error was computed between estimated and actual Hgb values; 95% of the percent errors ranged from –13.2% to 20.1%. The standard deviation of percent errors was 7.9% overall. When samples were further divided according to CBC Hgb concentration (low, normal or high), the standard deviation of percent error was 6.7% when Hgb<13 g/dL [130 g/L], 8.9% when Hgb 13–20 g/dL [130–200 g/L], and 6.5% when Hgb>20 g/dL [200 g/L]. The coefficient of variability among the 4 individual POC readings was 3.4%.ConclusionsA smartphone‐based photometric method for measuring Hgb represents a clinically useful POC alternative to a standard laboratory Hgb measurement. There was excellent intrasample reproducibility, and the standard deviation of percent errors was relatively constant across CBC ranges. Additional sampling of patients with a greater range of diseases and biochemical abnormalities that may influence spectrophotometric assays (ie, abnormal bilirubin, icterus, lipemia, hemolysis) is warranted to extend the findings of this study.
Perifosine Mechanisms of Action in Leishmania Species
Authors: López-Arencibia Atteneri , Martín-Navarro Carmen , Sifaoui Ines , Reyes-Batlle María , Wagner Carolina , Lorenzo-Morales Jacob , Maciver Sutherland K. , Piñero José E. 
Published: January 2017

ABSTRACT

Here the mechanism by which perifosine induced cell death in
Leishmania donovani
and
Leishmania amazonensis
is described. The drug reduced
Leishmania
mitochondrial membrane potential and decreased cellular ATP levels while increasing phosphatidylserine externalization. Perifosine did not increase membrane permeabilization. We also found that the drug inhibited the phosphorylation of Akt in the parasites. These results highlight the potential use of perifosine as an alternative to miltefosine against
Leishmania
.
Pharmacodynamics of Ceftaroline plus Ampicillin against Enterococcus faecalis in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model of Simulated Endocardial Vegetations
Authors: Werth Brian J. , Shireman Laura M. 
Published: January 2017

ABSTRACT

The combination of ampicillin plus ceftaroline has been suggested to be more reliably synergistic against
Enterococcus faecalis
than ampicillin plus ceftriaxone using time-kill methods. The purpose of this study was to determine if this trend persists in a two-compartment model of simulated endocardial vegetations (SEV) using clinically relevant pharmacokinetic exposures of these antimicrobials. Three clinically derived
E. faecalis
strains were included in the study. The MICs of study antimicrobials were determined by broth microdilution. Simulations of ampicillin (2 g every 4 h [q4h]; maximum concentration of drug in serum [
C
max
], 72.4 mg/liter; half-life [
t
1/2
], 1.9 h), ceftaroline-fosamil (600 mg q8h;
C
max
, 21.3 mg/liter;
t
1/2
, 2.66 h), ceftriaxone (
C
max
, 257 mg/liter;
t
1/2
, 8 h), and ampicillin plus ceftaroline and ampicillin plus ceftriaxone were evaluated against 3 strains of
E. faecalis
isolated from patients with endocarditis in an
in vitro
PK/PD SEV model over 72 h, with a starting inoculum of ∼9 log
10
CFU/g. All strains were susceptible to ampicillin (MIC, ≤2 mg/liter). Ceftaroline MICs varied from 2 to 16 mg/liter. All strains had ceftriaxone MICs of 256 mg/liter. W04 and W151 exhibited high-level aminoglycoside resistance but W07 did not. Ampicillin plus ceftaroline resulted in significantly greater reductions in CFU per gram by 72 h than ampicillin for all strains (
P
≤ 0.025) than ampicillin plus ceftriaxone for W04 (
P
= 0.019) but not W07 or W151 (
P
≥ 0.15). A 4-fold increase in ampicillin MIC was observed for W07 at 72 h, but this was prevented by the addition of ceftaroline or ceftriaxone. The combination of ampicillin plus ceftaroline appears to be at least as efficacious as ampicillin plus ceftriaxone and may lead to improved activity against some strains of
E. faecalis
, but these differences may be small and the clinical significance should not be overestimated.
Determinants of Antibacterial Spectrum and Resistance Potential of the Elongation Factor G Inhibitor Argyrin B in Key Gram-Negative Pathogens
Authors: Jones Adriana K. , Woods Angela L. , Takeoka Kenneth T. , Shen Xiaoyu , Wei Jun-Rong , Caughlan Ruth E. , Dean Charles R. 
Published: January 2017

ABSTRACT

Argyrins are natural products with antibacterial activity against Gram-negative pathogens, such as
Pseudomonas aeruginosa
,
Burkholderia multivorans
, and
Stenotrophomonas maltophilia
. We previously showed that argyrin B targets elongation factor G (FusA). Here, we show that argyrin B activity against
P. aeruginosa
PAO1 (MIC = 8 μg/ml) was not affected by deletion of the MexAB-OprM, MexXY-OprM, MexCD-OprJ, or MexEF-OprN efflux pump. However, argyrin B induced expression of MexXY, causing slight but reproducible antagonism with the MexXY substrate antibiotic ciprofloxacin. Argyrin B activity against
Escherichia coli
increased in a strain with nine
tolC
efflux pump partner genes deleted. Complementation experiments showed that argyrin was effluxed by AcrAB, AcrEF, and MdtFX. Argyrin B was inactive against
Acinetobacter baumannii
. Differences between
A. baumannii
and
P. aeruginosa
FusA proteins at key residues for argyrin B interaction implied that natural target sequence variation impacted antibacterial activity. Consistent with this, expression of the sensitive
P. aeruginosa
FusA1 protein in
A. baumannii
conferred argyrin susceptibility, whereas resistant variants did not. Argyrin B was active against
S. maltophilia
(MIC = 4 μg/ml). Spontaneous resistance occurred at high frequency in the bacterium (circa 10
−7
), mediated by mutational inactivation of
fusA1
rather than by amino acid substitutions in the target binding region. This strongly suggested that resistance occurred at high frequency through loss of the sensitive FusA1, leaving an alternate argyrin-insensitive elongation factor. Supporting this, an additional
fusA
-like gene (
fusA2
) is present in
S. maltophilia
that was strongly upregulated in response to mutational loss of
fusA1
.
Resistance to Thiacetazone Derivatives Active against Mycobacterium abscessus Involves Mutations in the MmpL5 Transcriptional Repressor MAB_4384
Authors: Halloum Iman , Viljoen Albertus , Khanna Varun , Craig Derek , Bouchier Christiane , Brosch Roland , Coxon Geoffrey , Kremer Laurent 
Published: January 2017

ABSTRACT

Available chemotherapeutic options are very limited against
Mycobacterium abscessus
, which imparts a particular challenge in the treatment of cystic fibrosis (CF) patients infected with this rapidly growing mycobacterium. New drugs are urgently needed against this emerging pathogen, but the discovery of active chemotypes has not been performed intensively. Interestingly, however, the repurposing of thiacetazone (TAC), a drug once used to treat tuberculosis, has increased following the deciphering of its mechanism of action and the detection of significantly more potent analogues. We therefore report studies performed on a library of 38 TAC-related derivatives previously evaluated for their antitubercular activity. Several compounds, including D6, D15, and D17, were found to exhibit potent activity
in vitro
against
M. abscessus
,
Mycobacterium massiliense
, and
Mycobacterium bolletii
clinical isolates from CF and non-CF patients. Similar to TAC in
Mycobacterium tuberculosis
, the three analogues act as prodrugs in
M. abscessus
, requiring bioactivation by the EthA enzyme, MAB_0985. Importantly, mutations in the transcriptional TetR repressor MAB_4384, with concomitant upregulation of the divergently oriented adjacent genes encoding an MmpS5/MmpL5 efflux pump system, accounted for high cross-resistance levels among all three compounds. Overall, this study uncovered a new mechanism of drug resistance in
M. abscessus
and demonstrated that simple structural optimization of the TAC scaffold can lead to the development of new drug candidates against
M. abscessus
infections.
Bacterium-Derived Cell-Penetrating Peptides Deliver Gentamicin To Kill Intracellular Pathogens
Authors: Gomarasca Marta , F. C. Martins Thaynan , Greune Lilo , Hardwidge Philip R. , Schmidt M. Alexander , Rüter Christian 
Published: January 2017

ABSTRACT

Commonly used antimicrobials show poor cellular uptake and often have limited access to intracellular targets, resulting in low antimicrobial activity against intracellular pathogens. An efficient delivery system to transport these drugs to the intracellular site of action is needed. Cell-penetrating peptides (CPPs) mediate the internalization of biologically active molecules into the cytoplasm. Here, we characterized two CPPs, α1H and α2H, derived from the
Yersinia enterocolitica
YopM effector protein. These CPPs, as well as Tat (
trans
-activator of transcription) from HIV-1, were used to deliver the antibiotic gentamicin to target intracellular bacteria. The YopM-derived CPPs penetrated different endothelial and epithelial cells to the same extent as Tat. CPPs were covalently conjugated to gentamicin, and CPP-gentamicin conjugates were used to target infected cells to kill multiple intracellular Gram-negative pathogenic bacteria, including
Escherichia coli
K1,
Salmonella enterica
serovar Typhimurium, and
Shigella flexneri
. Taken together, CPPs show great potential as delivery vehicles for antimicrobial agents and may contribute to the generation of new therapeutic tools to treat infectious diseases caused by intracellular pathogens.
Plasmidic
qnr
Genes Confer Clinical Resistance to Ciprofloxacin under Urinary Tract Physiological Conditions
Authors: Martín-Gutiérrez Guillermo , Rodríguez-Martínez José Manuel , Pascual Álvaro , Rodríguez-Beltrán Jerónimo , Blázquez Jesús 
Published: January 2017

ABSTRACT

Escherichia coli
variants expressing plasmid-mediated
qnr
genes are usually susceptible to fluoroquinolones by standard susceptibility testing. Here we show that, under specific urinary tract physiological conditions, susceptible laboratory and clinical strains harboring
qnr
determinants become fully resistant to ciprofloxacin (CIP). Therefore, physiological conditions, mainly urine pH values, should be considered when performing susceptibility testing of CIP activity against
E. coli
in treating urinary tract infection (UTI) and for selecting appropriate antibiotics for UTI treatment.
Specific Glucoside Transporters Influence Septal Structure and Function in the Filamentous, Heterocyst-Forming Cyanobacterium Anabaena sp. Strain PCC 7120
Authors: Nieves-Morión Mercedes , Lechno-Yossef Sigal , López-Igual Rocío , Frías José E. , Mariscal Vicente , Nürnberg Dennis J. , Mullineaux Conrad W. , Wolk C. Peter , Flores Enrique 
Published: January 2017

ABSTRACT

When deprived of combined nitrogen, some filamentous cyanobacteria contain two cell types: vegetative cells that fix CO
2
through oxygenic photosynthesis and heterocysts that are specialized in N
2
fixation. In the diazotrophic filament, the vegetative cells provide the heterocysts with reduced carbon (mainly in the form of sucrose) and heterocysts provide the vegetative cells with combined nitrogen. Septal junctions traverse peptidoglycan through structures known as nanopores and appear to mediate intercellular molecular transfer that can be traced with fluorescent markers, including the sucrose analog esculin (a coumarin glucoside) that is incorporated into the cells. Uptake of esculin by the model heterocyst-forming cyanobacterium
Anabaena
sp. strain PCC 7120 was inhibited by the α-glucosides sucrose and maltose. Analysis of
Anabaena
mutants identified components of three glucoside transporters that move esculin into the cells: GlsC (Alr4781) and GlsP (All0261) are an ATP-binding subunit and a permease subunit of two different ABC transporters, respectively, and HepP (All1711) is a major facilitator superfamily (MFS) protein that was shown previously to be involved in formation of the heterocyst envelope. Transfer of fluorescent markers (especially calcein) between vegetative cells of
Anabaena
was impaired by mutation of glucoside transporter genes. GlsP and HepP interact in bacterial two-hybrid assays with the septal junction-related protein SepJ, and GlsC was found to be necessary for the formation of a normal number of septal peptidoglycan nanopores and for normal subcellular localization of SepJ. Therefore, beyond their possible role in nutrient uptake in
Anabaena
, glucoside transporters influence the structure and function of septal junctions.

IMPORTANCE
Heterocyst-forming cyanobacteria have the ability to perform oxygenic photosynthesis and to assimilate atmospheric CO
2
and N
2
. These organisms grow as filaments that fix these gases specifically in vegetative cells and heterocysts, respectively. For the filaments to grow, these types of cells exchange nutrients, including sucrose, which serves as a source of reducing power and of carbon skeletons for the heterocysts. Movement of sucrose between cells in the filament takes place through septal junctions and has been traced with a fluorescent sucrose analog, esculin, that can be taken up by the cells. Here, we identified α-glucoside transporters of
Anabaena
that mediate uptake of esculin and, notably, influence septal structure and the function of septal junctions.
The Gut Microbiome of the Vector
Lutzomyia longipalpis
Is Essential for Survival of
Leishmania infantum
Authors: Kelly Patrick H. , Bahr Sarah M. , Serafim Tiago D. , Ajami Nadim J. , Petrosino Joseph F. , Meneses Claudio , Kirby John R. , Valenzuela Jesus G. , Kamhawi Shaden , Wilson Mary E. 
Published: January 2017

ABSTRACT

The vector-borne disease leishmaniasis, caused by
Leishmania
species protozoa, is transmitted to humans by phlebotomine sand flies. Development of
Leishmania
to infective metacyclic promastigotes in the insect gut, a process termed metacyclogenesis, is an essential prerequisite for transmission. Based on the hypothesis that vector gut microbiota influence the development of virulent parasites, we sequenced midgut microbiomes in the sand fly
Lutzomyia longipalpis
with or without
Leishmania infantum
infection. Sucrose-fed sand flies contained a highly diverse, stable midgut microbiome. Blood feeding caused a decrease in microbial richness that eventually recovered. However, bacterial richness progressively decreased in
L. infantum-
infected sand flies.
Acetobacteraceae
spp. became dominant and numbers of
Pseudomonadaceae
spp. diminished coordinately as the parasite underwent metacyclogenesis and parasite numbers increased. Importantly, antibiotic-mediated perturbation of the midgut microbiome rendered sand flies unable to support parasite growth and metacyclogenesis. Together, these data suggest that the sand fly midgut microbiome is a critical factor for
Leishmania
growth and differentiation to its infective state prior to disease transmission.

IMPORTANCE
Leishmania infantum
, a parasitic protozoan causing fatal visceral leishmaniasis, is transmitted to humans through the bite of the sand fly
Lutzomyia longipalpis
. Development of the parasite to its virulent metacyclic state occurs in the sand fly gut. In this study, the microbiota within the
Lu. longipalpis
midgut was delineated by 16S ribosomal DNA (rDNA) sequencing, revealing a highly diverse community composition that lost diversity as parasites developed to their metacyclic state and increased in abundance in infected flies. Perturbing sand fly gut microbiota with an antibiotic cocktail, which alone had no effect on either the parasite or the fly, arrested both the development of virulent parasites and parasite expansion. These findings indicate the importance of bacterial commensals within the insect vector for the development of virulent pathogens, and raise the possibility that impairing the microbial composition within the vector might represent a novel approach to control of vector-borne diseases.