bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterisation of tobacco microRNA transcriptome using high‐throughput sequencing
Authors: Gao J. , Yin F. , Liu M. , Luo M. , Qin C. , Yang A. , Yang S. , Zhang Z. , Shen Y. , Lin H. , Pan G. 
Published: October 2014

AbstractMicroRNAs (miRNAs) are post‐transcriptional regulators that are involved in numerous biological processes in plants. In this study, we investigate miRNAs in Honghua Dajinyuan, an agronomically important species of tobacco in China. Here, we report a comprehensive analysis of miRNA expression profiles in the leaf, stem and root using a high‐throughput sequencing approach. A total of 165 miRNAs, representing 55 conserved families, and 50 novel miRNAs, representing 19 families, were identified in three libraries. In addition, 12 miRNAs were randomly selected from a differentially expressed conserved miRNA family in three libraries with expression alterations and subjected to qRT‐PCR validation. Of these, the expression level of nta‐miR167d is highly enriched in the leaf tissue. In addition, the expression level of nta‐miR319a is prominently enriched in the stem, while nta‐miR160c is highly enriched in the root. Moreover, the target prediction showed that most of the targets coded for transcription factors that are involved in cellular and metabolic processes. GO analysis showed that most of the targets were involved in organelle function, served binding functions, and take part in cellular and metabolic processes. This study helps shed new light on understanding the role of miRNAs in different parts of the tobacco plant and adds a significant number of novel miRNAs to the tobacco miRNA transcriptome.
Active Political Parenting: Youth Contributions During Election Campaigns*
Authors: McDevitt Michael , Kiousis Spiro 
Published: October 2014

ObjectiveThe etiology of active parenting remains almost entirely unexplored in political socialization. Applying ecological and dialectic perspectives, we propose a model ofdevelopmental provocationto capture contributions of youth to a politicization of parenting during campaigns.MethodsParent‐youth dyads in Arizona, Colorado, and Florida were interviewed across two election cycles. Adolescent respondents were juniors and seniors during a midterm campaign, and old enough to vote during the subsequent presidential election.ResultsYouth news attention, opposition to U.S. military involvement, and first‐time voting contributed to conditional change in active political parenting across campaigns, and these activities were more consequential than corresponding behaviors of parents.ConclusionsParenting is not driven primarily by political expertise readily available and deployed in family interaction; of greater consequence is the observable development of youth. A child's potential for political growth is thereby ingrained in an evolving relationship that periodically demands more and more from parents.
Galois representations attached to moments of Kloosterman sums and conjectures of Evans
Authors: Yun Zhiwei , Vincent Christelle 
Published: October 2014

AbstractKloosterman sums for a finite field $\mathbb{F}_{p}$ arise as Frobenius trace functions of certain local systems defined over $\mathbb{G}_{m,\mathbb{F}_{p}}$. The moments of Kloosterman sums calculate the Frobenius traces on the cohomology of tensor powers (or symmetric powers, exterior powers, etc.) of these local systems. We show that when $p$ ranges over all primes, the moments of the corresponding Kloosterman sums for $\mathbb{F}_{p}$ arise as Frobenius traces on a continuous $\ell$-adic representation of $\text{Gal}(\overline{\mathbb{Q}}/\mathbb{Q})$ that comes from geometry. We also give bounds on the ramification of these Galois representations. All of this is done in the generality of Kloosterman sheaves attached to reductive groups introduced by Heinloth, Ngô and Yun [Ann. of Math. (2) 177 (2013), 241–310]. As an application, we give proofs of conjectures of Evans [Proc. Amer. Math. Soc. 138 (2010), 517–531; Israel J. Math. 175 (2010), 349–362] expressing the seventh and eighth symmetric power moments of the classical Kloosterman sum in terms of Fourier coefficients of explicit modular forms. The proof for the eighth symmetric power moment conjecture relies on the computation done in Appendix B by C. Vincent.
Explicit Kummer varieties of hyperelliptic Jacobian threefolds
Authors: Müller J. Steffen 
Published: October 2014

AbstractWe explicitly construct the Kummer variety associated to the Jacobian of a hyperelliptic curve of genus 3 that is defined over a field of characteristic not equal to 2 and has a rational Weierstrass point defined over the same field. We also construct homogeneous quartic polynomials on the Kummer variety and show that they represent the duplication map using results of Stoll.Supplementary materials are available with this article.
Assessment of the Induction of Dormant Ring Stages in Plasmodium falciparum Parasites by Artemisone and Artemisone Entrapped in Pheroid Vesicles
In Vitro
Authors: Grobler Lizette , Chavchich Marina , Haynes Richard K. , Edstein Michael D. , Grobler Anne F. 
Published: October 2014

ABSTRACT

The
in vitro
antimalarial activities of artemisone and artemisone entrapped in Pheroid vesicles were compared, as was their ability to induce dormancy in
Plasmodium falciparum
. There was no increase in the activity of artemisone entrapped in Pheroid vesicles against multidrug-resistant
P. falciparum
lines. Artemisone induced the formation of dormant ring stages similar to dihydroartemisinin. Thus, the Pheroid delivery system neither improved the activity of artemisone nor prevented the induction of dormant rings.
Quinacrine Inhibits Candida albicans Growth and Filamentation at Neutral pH
Authors: Kulkarny Vibhati V. , Chavez-Dozal Alba , Rane Hallie S. , Jahng Maximillian , Bernardo Stella M. , Parra Karlett J. , Lee Samuel A. 
Published: October 2014

ABSTRACT

Candida albicans
is a common cause of catheter-related bloodstream infections (CR-BSI), in part due to its strong propensity to form biofilms. Drug repurposing is an approach that might identify agents that are able to overcome antifungal drug resistance within biofilms. Quinacrine (QNC) is clinically active against the eukaryotic protozoan parasites
Plasmodium
and
Giardia
. We sought to investigate the antifungal activity of QNC against
C. albicans
biofilms.
C. albicans
biofilms were incubated with QNC at serially increasing concentrations (4 to 2,048 μg/ml) and assessed using a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2
H
-tetrazolium-5-carboxanilide (XTT) assay in a static microplate model. Combinations of QNC and standard antifungals were assayed using biofilm checkerboard analyses. To define a mechanism of action, QNC was assessed for the inhibition of filamentation, effects on endocytosis, and pH-dependent activity. High-dose QNC was effective for the prevention and treatment of
C. albicans
biofilms
in vitro
. QNC with fluconazole had no interaction, while the combination of QNC and either caspofungin or amphotericin B demonstrated synergy. QNC was most active against planktonic growth at alkaline pH. QNC dramatically inhibited filamentation. QNC accumulated within vacuoles as expected and caused defects in endocytosis. A tetracycline-regulated
VMA3
mutant lacking vacuolar ATPase (V-ATPase) function demonstrated increased susceptibility to QNC. These experiments indicate that QNC is active against
C. albicans
growth in a pH-dependent manner. Although QNC activity is not biofilm specific, QNC is effective in the prevention and treatment of biofilms. QNC antibiofilm activity likely occurs via several independent mechanisms: vacuolar alkalinization, inhibition of endocytosis, and impaired filamentation. Further investigation of QNC for the treatment and prevention of biofilm-related
Candida
CR-BSI is warranted.
Within-Population Distribution of Trimethoprim Resistance in Escherichia coli before and after a Community-Wide Intervention on Trimethoprim Use
Authors: Sundqvist Martin , Granholm Susanne , Naseer Umaer , Rydén Patrik , Brolund Alma , Sundsfjord Arnfinn , Kahlmeter Gunnar , Johansson Anders 
Published: October 2014

ABSTRACT

A 2-year prospective intervention on the prescription of trimethoprim reduced the use by 85% in a health care region with 178,000 inhabitants. Here, we performed before-and-after analyses of the within-population distribution of trimethoprim resistance in
Escherichia coli
. Phylogenetic and population genetic methods were applied to multilocus sequence typing data of 548 consecutively collected
E. coli
isolates from clinical urinary specimens. Results were analyzed in relation to antibiotic susceptibility and the presence and genomic location of different trimethoprim resistance gene classes. A total of 163
E. coli
sequence types (STs) were identified, of which 68 were previously undescribed. The isolates fell into one of three distinct genetic clusters designated BAPS 1 (
E. coli
phylogroup B2), BAPS 2 (phylogroup A and B1), and BAPS 3 (phylogroup D), each with a similar frequency before and after the intervention. BAPS 2 and BAPS 3 were positively and BAPS 1 was negatively associated with trimethoprim resistance (odds ratios of 1.97, 3.17, and 0.26, respectively). In before-and-after analyses, trimethoprim resistance frequency increased in BAPS 1 and decreased in BAPS 2. Resistance to antibiotics other than trimethoprim increased in BAPS 2. Analysis of the genomic location of different trimethoprim resistance genes in isolates of ST69, ST58, and ST73 identified multiple independent acquisition events in isolates of the same ST. The results show that despite a stable overall resistance frequency in
E. coli
before and after the intervention, marked within-population changes occurred. A decrease of resistance in one major genetic cluster was masked by a reciprocal increase in another major cluster.
First Report of NDM-1-Producing Acinetobacter baumannii Sequence Type 25 in Brazil
Authors: Pillonetto Marcelo , Arend Lavinia , Vespero Eliana Carolina , Pelisson Marsileni , Chagas Thiago Pavoni Gomes , Carvalho-Assef Ana Paula D'Alincourt , Asensi Marise Dutra 
Published: October 2014

ABSTRACT

New Delhi metallo-β-lactamase 1 (NDM-1) was first identified in Brazil in
Enterobacter hormaechei
and
Providencia rettgeri
in 2013. Here, we describe the first case of NDM-1-producing
Acinetobacter baumannii
sequence type 25 isolated from the urinary tract of a 71-year-old man who died of multiple complications, including
A. baumannii
infection. The NDM-1 gene was detected by quantitative PCR, and its sequence confirmed its presence in an ∼100-kb plasmid.
Crystal Structures of Klebsiella pneumoniae Dihydrofolate Reductase Bound to Propargyl-Linked Antifolates Reveal Features for Potency and Selectivity
Authors: Lamb Kristen M. , Lombardo Michael N. , Alverson Jeremy , Priestley Nigel D. , Wright Dennis L. , Anderson Amy C. 
Published: October 2014

ABSTRACT

Resistance to the antibacterial antifolate trimethoprim (TMP) is increasing in members of the family
Enterobacteriaceae
, driving the design of next-generation antifolates effective against these Gram-negative pathogens. The propargyl-linked antifolates are potent inhibitors of dihydrofolate reductases (DHFR) from several TMP-sensitive and -resistant species, including
Klebsiella pneumoniae
. Recently, we have determined that these antifolates inhibit the growth of strains of
K. pneumoniae
, some with MIC values of 1 μg/ml. In order to further the design of potent and selective antifolates against members of the
Enterobacteriaceae
, we determined the first crystal structures of
K. pneumoniae
DHFR bound to two of the propargyl-linked antifolates. These structures highlight that interactions with Leu 28, Ile 50, Ile 94, and Leu 54 are necessary for potency; comparison with structures of human DHFR bound to the same inhibitors reveal differences in residues (N64E, P61G, F31L, and V115I) and loop conformations (residues 49 to 53) that may be exploited for selectivity.
In Vitro
Activity of Human-Simulated Epithelial Lining Fluid Exposures of Ceftaroline, Ceftriaxone, and Vancomycin against Methicillin-Susceptible and -Resistant Staphylococcus aureus
Authors: MacVane Shawn H. , So Wonhee , Nicolau David P. , Kuti Joseph L. 
Published: October 2014

ABSTRACT

Staphylococcus aureus
, including methicillin-susceptible (MSSA) and -resistant (MRSA) strains, is an important pathogen of bacterial pneumonia. As antibiotic concentrations at the site of infection are responsible for killing, we investigated the activity of human-simulated epithelial lining fluid (ELF) exposures of three antibiotics (ceftaroline, ceftriaxone, and vancomycin) commonly used for treatment of
S. aureus
pneumonia. An
in vitro
pharmacodynamic model was used to simulate ELF exposures of vancomycin (1 g every 12 h [q12h]), ceftaroline (600 mg q12h and q8h), and ceftriaxone (2 g q24h and q12h). Four
S. aureus
isolates (2 MSSA and 2 MRSA) were evaluated over 72 h with a starting inoculum of ∼10
6
CFU/ml. Time-kill curves were constructed, and microbiological response (change in log
10
CFU/ml from 0 h and the area under the bacterial killing and regrowth curve [AUBC]) was assessed in duplicate. The change in 72-h log
10
CFU/ml was largest for ceftaroline q8h (reductions of >3 log
10
CFU/ml against all strains). This regimen also achieved the lowest AUBC against all organisms (
P
< 0.05). Vancomycin produced reliable bacterial reductions of 0.9 to 3.3 log
10
CFU/ml, while the activity of ceftaroline q12h was more variable (reductions of 0.2 to 2.3 log
10
CFU/ml against 3 of 4 strains). Both regimens of ceftriaxone were poorly active against MSSA tested (0.1 reduction to a 1.8-log
10
CFU/ml increase). Against these
S. aureus
isolates, ELF exposures of ceftaroline 600 mg q8h exhibited improved antibacterial activity compared with ceftaroline 600 mg q12h and vancomycin, and therefore, this q8h regimen deserves further evaluation for the treatment of bacterial pneumonia. These data also suggest that ceftriaxone should be avoided for
S. aureus
pneumonia.
Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock
Authors: Picard W. , Bazin F. , Clouzeau B. , Bui H.-N. , Soulat M. , Guilhon E. , Vargas F. , Hilbert G. , Bouchet S. , Gruson D. , Moore N. , Boyer A. 
Published: October 2014

ABSTRACT
To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.
KPC-Producing Klebsiella pneumoniae Strains That Harbor AAC(6′)-Ib Exhibit Intermediate Resistance to Amikacin
Authors: Bremmer Derek N. , Clancy Cornelius J. , Press Ellen G. , Almaghrabi Reem , Chen Liang , Doi Yohei , Nguyen M. Hong , Shields Ryan K. 
Published: October 2014

ABSTRACT

The aminoglycoside-modifying enzyme AAC(6′)-Ib is common among carbapenem-resistant
Klebsiella pneumoniae
(CR-Kp) strains. We investigated amikacin (AMK) activity against 20 AAC(6′)-Ib-producing CR-Kp strains. MICs clustered at 16 to 32 μg/ml. By the time-kill study, AMK (1× and 4× the MIC) was bactericidal against 30% and 85% of the strains, respectively. At achievable human serum concentrations, however, the majority of strains showed regrowth, suggesting that AAC(6′)-Ib confers intermediate AMK resistance. AMK and trimethoprim-sulfamethoxazole (TMP-SMX) were synergistic against 90% of the strains, indicating that the combination may overcome resistance.
Oral Administration of the Broad-Spectrum Antibiofilm Compound Toremifene Inhibits Candida albicans and Staphylococcus aureus Biofilm Formation
In Vivo
Authors: De Cremer Kaat , Delattin Nicolas , De Brucker Katrijn , Peeters Annelies , Kucharíková Soña , Gerits Evelien , Verstraeten Natalie , Michiels Jan , Van Dijck Patrick , Cammue Bruno P. A. , Thevissen Karin 
Published: October 2014

ABSTRACT

We here report on the
in vitro
activity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, including
Candida albicans
,
Candida glabrata
,
Candida dubliniensis
,
Candida krusei
,
Pseudomonas aeruginosa
,
Staphylococcus aureus
, and
Staphylococcus epidermidis
. We validated the
in vivo
efficacy of orally administered toremifene against
C. albicans and S. aureus
biofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound.
Pharmacokinetics, Biodistribution, and Toxicity of Folic Acid-Coated Antiretroviral Nanoformulations
Authors: Gautam Nagsen , Puligujja Pavan , Balkundi Shantanu , Thakare Rhishikesh , Liu Xin-Ming , Fox Howard S. , McMillan JoEllyn , Gendelman Howard E. , Alnouti Yazen 
Published: October 2014

ABSTRACT
The drug delivery platform for folic acid (FA)-coated nanoformulated ritonavir (RTV)-boosted atazanavir (FA-nanoATV/r) using poloxamer 407 was developed to enhance cell and tissue targeting for a range of antiretroviral drugs. Such formulations would serve to extend the drug half-life while improving the pharmacokinetic profile and biodistribution to reservoirs of human immunodeficiency virus (HIV) infection. To this end, we now report enhanced pharmacokinetics and drug biodistribution with limited local and systemic toxicities of this novel nanoformulation. The use of FA as a targeting ligand for nanoATV/r resulted in plasma and tissue drug concentrations up to 200-fold higher compared to equimolar doses of native drug. In addition, ATV and RTV concentrations in plasma from mice on a folate-deficient diet were up to 23-fold higher for mice administered FA-nanoATV/r than for mice on a normal diet. Compared to earlier nanoATV/r formulations, FA-nanoATV/r resulted in enhanced and sustained plasma and tissue ATV concentrations. In a drug interaction study, ATV plasma and tissue concentrations were up to 5-fold higher in mice treated with FA-nanoATV/r than in mice treated with FA-nanoATV alone. As observed in mice, enhanced and sustained plasma concentrations of ATV were observed in monkeys. NanoATV/r was associated with transient local inflammation at the site of injection. There were no systemic adverse reactions associated with up to 10 weeks of chronic exposure of mice or monkeys to FA-nanoATV/r.
Abdominal Candidiasis Is a Hidden Reservoir of Echinocandin Resistance
Authors: Shields Ryan K. , Nguyen M. Hong , Press Ellen G. , Clancy Cornelius J. 
Published: October 2014

ABSTRACT

FKS
mutant
Candida
isolates were recovered from 24% (6/25) of abdominal candidiasis patients exposed to echinocandin.
Candida glabrata
(29%) and
Candida albicans
(14%) mutants were identified. Multidrug-resistant bacteria were recovered from 83% of
FKS
mutant infections. Mutations were associated with prolonged echinocandin exposure (
P
= 0.01), breakthrough infections (
P
= 0.03), and therapeutic failures despite source control interventions (100%). Abdominal candidiasis is a hidden reservoir for the emergence of echinocandin-resistant
Candida
.
Transcription of the Streptococcus pyogenes Hyaluronic Acid Capsule Biosynthesis Operon Is Regulated by Previously Unknown Upstream Elements
Authors: Falaleeva Marina , Zurek Oliwia W. , Watkins Robert L. , Reed Robert W. , Ali Hadeel , Sumby Paul , Voyich Jovanka M. , Korotkova Natalia 
Published: October 2014

ABSTRACT

The important human pathogen
Streptococcus pyogenes
(group A
Streptococcus
[GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the
hasABC
operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription of
hasABC
, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion of
hasS
or of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through,
hasA
transcription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence.