bluuebunny/crossref_metadata_2025 huggingface dataset:
Annoyance survey by means of social media
Authors: Silva Bruno , Santos Gustavo , Eller Rogeria , Gjestland Truls
Published: February 2017

Social surveys have been the conventional means of evaluating the annoyance caused by transportation noise. Sampling and interviewing by telephone, mail, or in person are often costly and time consuming, however. Data collection by web-based survey methods are less costly and may be completed more quickly, and hence, could be conducted in countries with fewer resources. Such methods, however, raise issues about the generalizability and comparability of findings. These issues were investigated in a study of the annoyance of aircraft noise exposure around Brazil's Guarulhos Airport. The findings of 547 interviews obtained with the aid of Facebook advertisements and web-based forms were analysed with respect to estimated aircraft noise exposure levels at respondents' residences. The results were analysed to assess whether and how web-based surveys might yield generalizable noise dose-response relationships.
Sensorineural hearing loss enhances auditory sensitivity and temporal integration for amplitude modulation
Authors: Wallaert Nicolas , Moore Brian C. J. , Ewert Stephan D. , Lorenzi Christian
Published: February 2017

Amplitude-modulation detection thresholds (AMDTs) were measured at 40 dB sensation level for listeners with mild-to-moderate sensorineural hearing loss (age: 50–64 yr) for a carrier frequency of 500 Hz and rates of 2 and 20 Hz. The number of modulation cycles, N, varied between two and nine. The data were compared with AMDTs measured for young and older normal-hearing listeners [Wallaert, Moore, and Lorenzi (2016). J. Acoust. Soc. Am. 139, 3088–3096]. As for normal-hearing listeners, AMDTs were lower for the 2-Hz than for the 20-Hz rate, and AMDTs decreased with increasing N. AMDTs were lower for hearing-impaired listeners than for normal-hearing listeners, and the effect of increasing N was greater for hearing-impaired listeners. A computational model based on the modulation-filterbank concept and a template-matching decision strategy was developed to account for the data. The psychophysical and simulation data suggest that the loss of amplitude compression in the impaired cochlea is mainly responsible for the enhanced sensitivity and temporal integration of temporal envelope cues found for hearing-impaired listeners. The data also suggest that, for AM detection, cochlear damage is associated with increased internal noise, but preserved short-term memory and decision mechanisms.
Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2
Authors: Ler Lian Dee , Ghosh Sujoy , Chai Xiaoran , Thike Aye Aye , Heng Hong Lee , Siew Ee Yan , Dey Sucharita , Koh Liang Kai , Lim Jing Quan , Lim Weng Khong , Myint Swe Swe , Loh Jia Liang , Ong Pauline , Sam Xin Xiu , Huang Dachuan , Lim Tony , Tan Puay Hoon , Nagarajan Sanjanaa , Cheng Christopher Wai Sam , Ho Henry , Ng Lay Guat , Yuen John , Lin Po-Hung , Chuang Cheng-Keng , Chang Ying-Hsu , Weng Wen-Hui , Rozen Steven G. , Tan Patrick , Creasy Caretha L. , Pang See-Tong , McCabe Michael T. , Poon Song Ling , Teh Bin Tean
Published: February 2017

Bladder cancer with loss of KDM6A expression is vulnerable to inhibition of EZH2.
Surveillance of Omadacycline Activity against Clinical Isolates from a Global Collection (North America, Europe, Latin America, Asia-Western Pacific), 2010-2011
Authors: Pfaller Michael A. , Huband Michael D. , Rhomberg Paul R. , Flamm Robert K.
Published: February 2017

Omadacycline is a broad-spectrum aminomethylcycline in late-stage clinical development for the treatment of acute bacterial skin and skin structure infections and community-acquired pneumonia as an oral and an intravenous once-daily formulation. In this study, omadacycline and comparators were tested against 69,246 nonduplicate bacterial isolates collected prospectively during 2010 and 2011 from medical centers in Asia-Pacific (11,397 isolates), Europe (23,490 isolates), Latin America (8,038 isolates), and North America (26,321 isolates). Omadacycline was tested by broth microdilution following Clinical and Laboratory Standards Institute M07-A10 (2015) methods. A total of 99.9% of
Staphylococcus aureus
isolates were inhibited by ≤2 μg/ml of omadacycline (MIC
50/90
, 0.12/0.25 μg/ml), including 100.0% of methicillin-susceptible
S. aureus
isolates and 99.8% of methicillin-resistant
S. aureus
isolates. Omadacycline potencies were comparable for
Streptococcus pneumoniae
(MIC
50/90
, 0.06/0.06 μg/ml), viridans group streptococci (MIC
50/90
, 0.06/0.12 μg/ml), and beta-hemolytic streptococci (MIC
50/90
, 0.06/0.12 μg/ml) regardless of species and susceptibility to penicillin. Omadacycline was active against
Enterobacteriaceae
and was most active against
Escherichia coli
(MIC
50/90
, 0.5/2 μg/ml),
Enterobacter aerogenes
(MIC
50/90
, 2/4 μg/ml),
Klebsiella oxytoca
(MIC
50/90
, 1/4 μg/ml), and
Citrobacter
spp. (MIC
50/90
, 1/4 μg/ml). Omadacycline was active against
Haemophilus influenzae
(MIC
50/90
, 1/1 μg/ml) regardless of β-lactamase status and against
Moraxella catarrhalis
(MIC
50/90
, 0.12/0.25 μg/ml). The potent activity of omadacycline against Gram-positive and Gram-negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative infections may be a concern.
Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections
Authors: Lee Dong-Hwan , Kim Yong Kyun , Jin Kyubok , Kang Myoung Joo , Joo Young-Don , Kim Yang Wook , Moon Young Soo , Shin Jae-Gook , Kiem Sungmin
Published: February 2017

We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients (
n
= 37) with a creatinine clearance (CL
CR
) of 20 to 50 ml/min or >50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution (
V
/WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CL
CR
. The proposed equation to estimate doripenem CL in Korean patients was CL/WT = 0.109 × WT × (CL
CR
/57)
0.688
, where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was ≤1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility.
In Vitro
and
In Vivo
Antifungal Profile of a Novel and Long-Acting Inhaled Azole, PC945, on Aspergillus fumigatus Infection
Authors: Colley Thomas , Alanio Alexandre , Kelly Steven L. , Sehra Gurpreet , Kizawa Yasuo , Warrilow Andrew G. S. , Parker Josie E. , Kelly Diane E. , Kimura Genki , Anderson-Dring Lauren , Nakaoki Takahiro , Sunose Mihiro , Onions Stuart , Crepin Damien , Lagasse Franz , Crittall Matthew , Shannon Jonathan , Cooke Michael , Bretagne Stéphane , King-Underwood John , Murray John , Ito Kazuhiro , Strong Pete , Rapeport Garth
Published: February 2017

The profile of PC945, a novel triazole antifungal designed for administration via inhalation, was assessed in a range of
in vitro
and
in vivo
studies. PC945 was characterized as a potent, tightly binding inhibitor of
Aspergillus fumigatus
sterol 14α-demethylase (CYP51A and CYP51B) activity (50% inhibitory concentrations [IC
50
s], 0.23 μM and 0.22 μM, respectively) with characteristic type II azole binding spectra. Against 96 clinically isolated
A. fumigatus
strains, the MIC values of PC945 ranged from 0.032 to >8 μg/ml, while those of voriconazole ranged from 0.064 to 4 μg/ml. Spectrophotometric analysis of the effects of PC945 against itraconazole-susceptible and -resistant
A. fumigatus
growth yielded IC
50
(determined based on optical density [OD]) values of 0.0012 to 0.034 μg/ml, whereas voriconazole (0.019 to >1 μg/ml) was less effective than PC945. PC945 was effective against a broad spectrum of pathogenic fungi (with MICs ranging from 0.0078 to 2 μg/ml), including
Aspergillus terreus
,
Trichophyton rubrum
,
Candida albicans
,
Candida glabrata
,
Candida krusei
,
Cryptococcus gattii
,
Cryptococcus neoformans
, and
Rhizopus oryzae
(1 or 2 isolates each). In addition, when
A. fumigatus
hyphae or human bronchial cells were treated with PC945 and then washed, PC945 was found to be absorbed quickly into both target and nontarget cells and to produce persistent antifungal effects. Among temporarily neutropenic immunocompromised mice infected with
A. fumigatus
intranasally, 50% of the animals survived until day 7 when treated intranasally with PC945 at 0.56 μg/mouse, while posaconazole showed similar effects (44%) at 14 μg/mouse. This profile affirms that topical treatment with PC945 should provide potent antifungal activity in the lung.
Requirement of the CroRS Two-Component System for Resistance to Cell Wall-Targeting Antimicrobials in Enterococcus faecium
Authors: Kellogg Stephanie L. , Little Jaime L. , Hoff Jessica S. , Kristich Christopher J.
Published: February 2017

Enterococci are serious opportunistic pathogens that are resistant to many cell wall-targeting antibiotics. The CroRS two-component signaling system responds to antibiotic-mediated cell wall stress and is critical for resistance to cell wall-targeting antibiotics in
Enterococcus faecalis
. Here, we identify and characterize an orthologous two-component system found in
Enterococcus faecium
that is functionally equivalent to the CroRS system of
E. faecalis
. Deletion of
croRS
in
E. faecium
resulted in marked susceptibility to cell wall-targeting agents including cephalosporins and bacitracin, as well as moderate susceptibility to ampicillin and vancomycin. As in
E. faecalis
, exposure to bacitracin and vancomycin stimulates signaling through the CroRS system in
E. faecium
. Moreover, the CroRS system is critical in
E. faecium
for enhanced beta-lactam resistance mediated by overexpression of Pbp5. Expression of a Pbp5 variant that confers enhanced beta-lactam resistance cannot overcome the requirement for CroRS function. Thus, the CroRS system is a conserved signaling system that responds to cell wall stress to promote intrinsic resistance to important cell wall-targeting antibiotics in clinically relevant enterococci.
Mutations in
bla
KPC-3
That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases
Authors: Haidar Ghady , Clancy Cornelius J. , Shields Ryan K. , Hao Binghua , Cheng Shaoji , Nguyen M. Hong
Published: February 2017

We identified four
bla
KPC-3
mutations in ceftazidime-avibactam-resistant clinical
Klebsiella pneumoniae
isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis and transforming vectors into
Escherichia coli
, we conclusively demonstrated that mutant
bla
KPC-3
encoded enzymes that functioned as extended-spectrum β-lactamases; mutations directly conferred higher MICs of ceftazidime-avibactam and decreased the MICs of carbapenems and other β-lactams. Impact was strongest for the D179Y mutant, highlighting the importance of the KPC Ω-loop.
Enterobacter cloacae Complex Isolates Harboring
bla
NMC-A
or
bla
IMI
-Type Class A Carbapenemase Genes on Novel Chromosomal Integrative Elements and Plasmids
Authors: Boyd David A. , Mataseje Laura F. , Davidson Ross , Delport Johannes A. , Fuller Jeff , Hoang Linda , Lefebvre Brigitte , Levett Paul N. , Roscoe Diane L. , Willey Barbara M. , Mulvey Michael R.
Published: February 2017

Carbapenem-resistant
Enterobacter cloacae
complex isolates submitted to a reference laboratory from 2010 to 2015 were screened by PCR for seven common carbapenemase gene groups, namely, KPC, NDM, OXA-48, VIM, IMP, GES, and NMC-A/IMI. Nineteen of the submitted isolates (1.7%) were found to harbor Ambler class A
bla
NMC-A
or
bla
IMI
-type carbapenemases. All 19 isolates were resistant to at least one carbapenem but susceptible to aminoglycosides, trimethoprim-sulfamethoxazole, tigecycline, and ciprofloxacin. Most isolates (17/19) gave positive results with the Carba-NP test for phenotypic carbapenemase detection. Isolates were genetically diverse by pulsed-field gel electrophoresis macrorestriction analysis, multilocus sequence typing, and
hsp60
gene analysis. The genes were found in various
Enterobacter cloacae
complex species; however,
bla
NMC-A
was highly associated with
Enterobacter ludwigii
. Whole-genome sequencing and bioinformatics analysis revealed that all NMC-A (
n
= 10), IMI-1 (
n
= 5), and IMI-9 (
n
= 2) producers harbored the carbapenemase gene on EludIMEX-1-like integrative mobile elements (EcloIMEXs) located in the identical chromosomal locus. Two novel genes,
bla
IMI-5
and
bla
IMI-6
, were harbored on different IncFII-type plasmids.
Enterobacter cloacae
complex isolates harboring
bla
NMC-A/IMI
-type carbapenemases are relatively rare in Canada. Though mostly found integrated into the chromosome, some variants are located on plasmids that may enhance their mobility potential.
Active Multienzyme Assemblies for Long-Chain Olefinic Hydrocarbon Biosynthesis
Authors: Christenson James K. , Jensen Matthew R. , Goblirsch Brandon R. , Mohamed Fatuma , Zhang Wei , Wilmot Carrie M. , Wackett Lawrence P.
Published: February 2017

Bacteria from different phyla produce long-chain olefinic hydrocarbons derived from an OleA-catalyzed Claisen condensation of two fatty acyl coenzyme A (acyl-CoA) substrates, followed by reduction and oxygen elimination reactions catalyzed by the proteins OleB, OleC, and OleD. In this report, OleA, OleB, OleC, and OleD were individually purified as soluble proteins, and all were found to be essential for reconstituting hydrocarbon biosynthesis. Recombinant coexpression of tagged OleABCD proteins from
Xanthomonas campestris
in
Escherichia coli
and purification over His
6
and FLAG columns resulted in OleA separating, while OleBCD purified together, irrespective of which of the four Ole proteins were tagged. Hydrocarbon biosynthetic activity of copurified OleBCD assemblies could be reconstituted by adding separately purified OleA. Immunoblots of nondenaturing gels using anti-OleC reacted with
X. campestris
crude protein lysate indicated the presence of a large protein assembly containing OleC in the native host. Negative-stain electron microscopy of recombinant OleBCD revealed distinct large structures with diameters primarily between 24 and 40 nm. Assembling OleB, OleC, and OleD into a complex may be important to maintain stereochemical integrity of intermediates, facilitate the movement of hydrophobic metabolites between enzyme active sites, and protect the cell against the highly reactive β-lactone intermediate produced by the OleC-catalyzed reaction.

IMPORTANCE
Bacteria biosynthesize hydrophobic molecules to maintain a membrane, store carbon, and for antibiotics that help them survive in their niche. The hydrophobic compounds are often synthesized by a multidomain protein or by large multienzyme assemblies. The present study reports on the discovery that long-chain olefinic hydrocarbons made by bacteria from different phyla are produced by multienzyme assemblies in
X. campestris
. The OleBCD multienzyme assemblies are thought to compartmentalize and sequester olefin biosynthesis from the rest of the cell. This system provides additional insights into how bacteria control specific biosynthetic pathways.
Heterogeneity Confounds Establishment of “a” Model Microbial Strain
Authors: Keller Nancy P.
Published: February 2017

Aspergillus fumigatus
is a ubiquitous environmental mold and the leading cause of diverse human diseases ranging from allergenic bronchopulmonary aspergillosis (ABPA) to invasive pulmonary aspergillosis (IPA). Experimental investigations of the biology and virulence of this opportunistic pathogen have historically used a few type strains; however, it is increasingly observed with this fungus that heterogeneity among isolates potentially confounds the use of these reference isolates. Illustrating this point, Kowalski et al. (mBio 7:e01515-16, 2016,
https://doi.org/10.1128/mBio.01515-16
) demonstrated that variation in 16 environmental and clinical isolates of
A. fumigatus
correlated virulence with fitness in low oxygen, whereas Fuller et al. (mBio 7:e01517-16, 2016,
https://doi.org/10.1128/mBio.01517-16
) showed wide variation in light responses at a physiological and protein functionality level in 15
A. fumigatus
isolates. In both studies, two commonly used type strains, Af293 and CEA10, displayed significant differences in physiological responses to abiotic stimuli and virulence in a murine model of IPA.
A Natural ChimericPseudomonasBacteriocin with Novel Pore-Forming Activity Parasitizes the Ferrichrome Transporter
Authors: Ghequire Maarten G. K. , Kemland Lieselore , Anoz-Carbonell Ernesto , Buchanan Susan K. , De Mot René
Published: February 2017

Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently inhibit the toxin’s activity through formation of bacteriocin-immunity complexes or by insertion in the inner membrane, depending on the type of toxin module. We demonstrate strain-specific inhibitory activity for PmnH, aPseudomonasbacteriocin with an unprecedented dual-toxin architecture, hosting both a colicin M domain, potentially interfering with peptidoglycan synthesis, and a novel colicin N-type domain, a pore-forming module distinct from the colicin Ia-type domain inPseudomonas aeruginosapyocin S5. A downstream-linked gene product confers PmnH immunity upon susceptible strains. This protein, ImnH, has a transmembrane topology similar to that ofPseudomonascolicin M-like and pore-forming immunity proteins, although homology with either of these is essentially absent. The enhanced killing activity of PmnH under iron-limited growth conditions reflects parasitism of the ferrichrome-type transporter for entry into target cells, a strategy shown here to be used as well by monodomain colicin M-like bacteriocins from pseudomonads. The integration of a second type of toxin module in a bacteriocin gene could offer a competitive advantage against bacteria displaying immunity against only one of both toxic activities.

IMPORTANCEIn their continuous struggle for ecological space, bacteria face a huge load of contenders, including phylogenetically related strains that compete for the same niche. One important group of secreted antibacterial proteins assisting in eliminating these rivals are modular bacteriocins of Gram-negative bacteria, comprising a domain for docking onto the cell envelope of a target cell, a translocation domain enabling subsequent cellular entry, and a toxin module that kills target cells via enzymatic or pore-forming activity. We here demonstrate the antagonistic function of aPseudomonasbacteriocin with unique architecture that combines a putative enzymatic colicin M-like domain and a novel pore-forming toxin module. For target cell recognition and entry, this bacteriocin hybrid takes advantage of the ferrichrome transporter, also parasitized by enzymaticPseudomonasbacteriocins devoid of the pore-forming module. Bacteriocins with an expanded toxin potential may represent an inventive bacterial strategy to alleviate immunity in target cells.
Evolution and Epidemiology of Multidrug-Resistant
Klebsiella pneumoniae
in the United Kingdom and Ireland
Authors: Moradigaravand Danesh , Martin Veronique , Peacock Sharon J. , Parkhill Julian
Published: February 2017

Klebsiella pneumoniae
is a human commensal and opportunistic pathogen that has become a leading causative agent of hospital-based infections over the past few decades. The emergence and global expansion of hypervirulent and multidrug-resistant (MDR) clones of
K. pneumoniae
have been increasingly reported in community-acquired and nosocomial infections. Despite this, the population genomics and epidemiology of MDR
K. pneumoniae
at the national level are still poorly understood. To obtain insights into these, we analyzed a systematic large-scale collection of invasive MDR
K. pneumoniae
isolates from hospitals across the United Kingdom and Ireland. Using whole-genome phylogenetic analysis, we placed these in the context of previously sequenced
K. pneumoniae
populations from geographically diverse countries and identified their virulence and drug resistance determinants. Our results demonstrate that United Kingdom and Ireland MDR isolates are a highly diverse population drawn from across the global phylogenetic tree of
K. pneumoniae
and represent multiple recent international introductions that are mainly from Europe but in some cases from more distant countries. In addition, we identified novel genetic determinants underlying resistance to beta-lactams, gentamicin, ciprofloxacin, and tetracyclines, indicating that both increased virulence and resistance have emerged independently multiple times throughout the population. Our data show that MDR
K. pneumoniae
isolates in the United Kingdom and Ireland have multiple distinct origins and appear to be part of a globally circulating
K. pneumoniae
population.

IMPORTANCE
Klebsiella pneumoniae
is a major human pathogen that has been implicated in infections in healthcare settings over the past few decades. Antimicrobial treatment of
K. pneumoniae
infections has become increasingly difficult as a consequence of the emergence and spread of strains that are resistant to multiple antimicrobials. To better understand the spread of resistant
K. pneumoniae
, we studied the genomes of a large-scale population of extensively antimicrobial-resistant
K. pneumoniae
in the United Kingdom and Ireland by utilizing the fine resolution that whole-genome sequencing of pathogen genomes provides. Our results indicate that the
K. pneumoniae
population is highly diverse and that, in some cases, resistant strains appear to have spread across the country over a few years. In addition, we found evidence that some strains have acquired antimicrobial resistance genes independently, presumably in response to antimicrobial treatment.
Identification of a
Pseudomonas aeruginosa
PAO1 DNA Methyltransferase, Its Targets, and Physiological Roles
Authors: Doberenz Sebastian , Eckweiler Denitsa , Reichert Olga , Jensen Vanessa , Bunk Boyke , Spröer Cathrin , Kordes Adrian , Frangipani Emanuela , Luong Khai , Korlach Jonas , Heeb Stephan , Overmann Jörg , Kaever Volkhard , Häussler Susanne
Published: February 2017

DNA methylation is widespread among prokaryotes, and most DNA methylation reactions are catalyzed by adenine DNA methyltransferases, which are part of restriction-modification (R-M) systems. R-M systems are known for their role in the defense against foreign DNA; however, DNA methyltransferases also play functional roles in gene regulation. In this study, we used single-molecule real-time (SMRT) sequencing to uncover the genome-wide DNA methylation pattern in the opportunistic pathogen
Pseudomonas aeruginosa
PAO1. We identified a conserved sequence motif targeted by an adenine methyltransferase of a type I R-M system and quantified the presence of N
6
-methyladenine using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Changes in the PAO1 methylation status were dependent on growth conditions and affected
P. aeruginosa
pathogenicity in a
Galleria mellonella
infection model. Furthermore, we found that methylated motifs in promoter regions led to shifts in sense and antisense gene expression, emphasizing the role of enzymatic DNA methylation as an epigenetic control of phenotypic traits in
P. aeruginosa
. Since the DNA methylation enzymes are not encoded in the core genome, our findings illustrate how the acquisition of accessory genes can shape the global
P. aeruginosa
transcriptome and thus may facilitate adaptation to new and challenging habitats.

IMPORTANCE
With the introduction of advanced technologies, epigenetic regulation by DNA methyltransferases in bacteria has become a subject of intense studies. Here we identified an adenosine DNA methyltransferase in the opportunistic pathogen
Pseudomonas aeruginosa
PAO1, which is responsible for DNA methylation of a conserved sequence motif. The methylation level of all target sequences throughout the PAO1 genome was approximated to be in the range of 65 to 85% and was dependent on growth conditions. Inactivation of the methyltransferase revealed an attenuated-virulence phenotype in the
Galleria mellonella
infection model. Furthermore, differential expression of more than 90 genes was detected, including the small regulatory RNA
prrF1
, which contributes to a global iron-sparing response via the repression of a set of gene targets. Our finding of a methylation-dependent repression of the antisense transcript of the
prrF1
small regulatory RNA significantly expands our understanding of the regulatory mechanisms underlying active DNA methylation in bacteria.
Fault-controlled dolomitization in a rift basin
Authors: Hollis Cathy , Bastesen Eivind , Boyce Adrian , Corlett Hilary , Gawthorpe Robert , Hirani Jesal , Rotevatn Atle , Whitaker Fiona
Published: February 2017

There are numerous examples of fault-controlled, so-called hydrothermal dolomite (HTD), many of which host economic mineral deposits or hydrocarbons, but there remains a lack of consensus as to how they form. In particular, multiple phases of diagenetic overprinting can obscure geochemical fingerprints. Study of a Cenozoic succession with a relatively simple burial history here provides new insights into the development of differentially dolomitized beds. The Hammam Faraun fault (HFF) block within the Suez Rift, Egypt, hosts both massive and stratabound dolostone bodies. Non-fabric-selective massive dolostone is limited to the damage zone of the fault, while fabric-selective stratabound dolostone bodies penetrate nearly 2 km into the footwall. Oligo-Miocene seawater is interpreted to have been drawn down discrete faults into a deep aquifer and convected upwards along the HFF. Escape of fluids from the incipient HFF into the lower Thebes Formation led to differential, stratabound dolomitization. Once the HFF breached the surface, fluid circulation focused along the fault plane to form younger, massive dolostone bodies. This study provides a snapshot of dolomitization during the earliest phases of extension, unobscured by subsequent recrystallization and geochemical modification. Contrary to many models, stratabound dolomitization preceded non-stratabound dolomitization. Fluids were hydrothermal, but with little evidence for rapid cooling and brecciation common to many HTD bodies. These results suggest that many of the features used to interpret and predict the geometry of HTD in the subsurface form during later phases of structural deformation, perhaps overprinting less structurally complex dolomite bodies.
Atypical case of preterm ovarian hyperstimulation syndrome
Authors: Durst Michelle A , Wicklow Brandy , Narvey Michael
Published: February 2017

Preterm ovarian hyperstimulation syndrome is a rare syndrome in which preterm infant girls have hypogastric, upper leg and labial swelling accompanied by elevated serum oestradiol levels and ovarian follicular cysts on ultrasound. Our case is an infant born at 23 weeks gestational age who at 30 weeks postconceptional age (PCA) developed elevated 17-hydroxyprogesterone on her newborn screen with associated clitoromegaly and a ventral groove on the inferior aspect of the erectile tissue. An initial pelvic ultrasound at 32 weeks PCA demonstrated a normal appearing uterus, but the ovaries were not visualised. At 39 weeks PCA, follicular ovarian cysts were noted bilaterally (31×26×21 mm on left and 38×25×36 mm on right). Without treatment, oestradiol and testosterone levels began normalising by 42 weeks PCA. After this point, the right ovarian cysts had resolved and the left ovarian cyst continued to diminish in size.
Right upper quadrant abdominal pain as the initial presentation of polyarteritis nodosa
Authors: Gago Ricardo , Shum Lee Ming , Vilá Luis M
Published: February 2017

Polyarteritis nodosa (PAN) is a necrotising vasculitis that involves medium and small vessels. PAN generally presents with constitutional, cutaneous, neurological, renal and gastrointestinal manifestations. However, PAN initially involving a single organ/system is uncommon. Here, we present a 42-year-old man who was hospitalised because of severe right upper quadrant abdominal pain that started 2 months before. Physical examination was remarkable for right upper quadrant abdominal tenderness. Abdominopelvic CT showed lymphadenopathy but no hepatic, gallbladder, pancreatic, intestinal or renal abnormalities. Abdominal angiography showed multiple small aneurysms located in the jejunal and hepatic arteries characteristic of PAN. He had a prompt and remarkable response to high-dose corticosteroids and oral cyclophosphamide. Our case, together with other reports, suggests that PAN should be considered in patients presenting with right upper abdominal pain. Timely diagnosis and treatment reduce the overall morbidity and mortality of the disease.
Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab
Authors: Thompson Grace , Pepperell Dominic , Lawrence Ian , McGettigan Benjamin David
Published: February 2017

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication.
Stress cardiomyopathy in a patient with hypertrophic cardiomyopathy and myocardial bridging
Authors: Benavides Miguel , Vinardell Juan M , Arenas Ivan , Santana Orlando
Published: February 2017

Stress cardiomyopathy is an acquired cardiomyopathy of unknown aetiology. It usually occurs in women over the age of 70 who have experienced physical or emotional stress. It is most commonly characterised by a transient, left ventricular systolic dysfunction in the apical portion and hyperkinesia in the basal segments, without obstructive coronary artery disease. Its association with obstructive hypertrophic cardiomyopathy and myocardial bridging is rare. Herein, we present such a case.
Genetic variation patterns of American chestnut populations at EST-SSRs
Authors: Gailing Oliver , Nelson C. Dana
Published: February 2017

The objective of this study is to analyze patterns of genetic variation at genic expressed sequence tag – simple sequence repeats (EST-SSRs) and at chloroplast DNA markers in populations of American chestnut (Castanea dentata Borkh.) to assist in conservation and breeding efforts. Allelic diversity at EST-SSRs decreased significantly from southwest to northeast along the Appalachian range, suggesting repeated founder events during postglacial migration. Comparatively high allelic diversity in Ontario, northwest of the Appalachian range, suggested more recent long-distance dispersal. Clinal variation of allele frequencies along the Appalachian axis was also in accordance with postglacial colonization from one refugium southwest of the Appalachian range. We observed clustering of the northwestern population from Ontario with southwestern populations and sharing of a rare chloroplast haplotype among western populations across the whole latitudinal range. This pattern is consistent with a divergence of postglacial migration routes and higher levels of more recent potentially human-mediated gene exchange between populations west of the Appalachian range. Population pairs east and west of the Appalachian axis showed pronounced allele frequency differences over a small geographic range. These patterns of genetic variation should be considered when sampling reproductive material for conservation and breeding.
The mechanical, optical and thermoelectric properties of MCoF3(M = K and Rb) compounds
Authors: Mubarak A. A.
Published: February 2017

This is an ab initio study instituted on the density functional theory (DFT) and the full-potential linearized augmented plane wave (FP-LAPW) calculations that are performed to analyze the mechanical, electronic, optical and thermoelectric properties of the cubic MCoF3compound (M = K and Rb). The studied compounds are found thermodynamically and mechanically stable. Moreover, these compounds are found to be elastically anisotropic and ductile. KCoF3and RbCoF3are classified as half-metallic and anti-ferromagnetic compounds. The optical properties are investigated from the dielectric function for the different energy ranges. The thermoelectric properties such as transport properties are determined as a function of temperature using BoltzTrape code in the range of 20–800 K. The present compounds are found to have p-type character. Also, the majority charge carriers are found to be electrons rather than hole. Useful mechanical, spintronic, optical and thermoelectric applications are predicted based upon the calculations.
Stability analysis of Einstein universe in f(𝒢,T) gravity
Authors: Sharif M. , Ikram Ayesha
Published: February 2017

This paper explores the stability of the Einstein universe against linear homogeneous perturbations in the background of [Formula: see text] gravity. We construct static as well as perturbed field equations and investigate stability regions for the specific forms of generic function [Formula: see text] corresponding to conserved as well as nonconserved energy-momentum tensor. We use the equation-of-state parameter to parameterize the stability regions. The graphical analysis shows that the suitable choice of parameters lead to stable regions of the Einstein universe.
The Message of “APEC Blue” for the Prevention and Control of Urban Air Pollution in China
Authors: ZHU Rong
Published: February 2017

Analysis of the meteorological conditions for atmospheric pollutant dispersion before and after the 2014 APEC meeting shows very significant effects of air pollution prevention and control measures on the meeting. It proves that the proper measures to control air pollution in the Beijing-Tianjin-Hebei Region are: establishing a regional emergency response mechanism to reduce emissions in the case of heavy air pollution, strengthening the local emergency response measures for emission reduction, and enhancing the early warning system for weather conditions conducive to heavy air pollution.
Numerical study for cohesive zone model in delamination analysis based on higher-order B-spline functions
Authors: Thai Tran Quoc , Rabczuk Timon , Zhuang Xiaoying
Published: February 2017

A numerical aspect of the implementation cohesive zone model for delamination analysis is presented in this work by employing interface elements and higher-order B-spline functions. The stress oscillation is addressed, and Newton–Cotes integration scheme is considered as a good candidate to overcome this phenomenon. In order to track the nonlinear equilibrium path, a general arc-length constraint named dissipation-based arc-length method is applied. A numerical example is presented to perform the ability of the formulation in predicting the delamination behavior of studied structures.
Zooming In on Plant Hormone Analysis: Tissue- and Cell-Specific Approaches
Authors: Novák Ondřej , Napier Richard , Ljung Karin
Published: February 2017

Plant hormones are a group of naturally occurring, low-abundance organic compounds that influence physiological processes in plants. Our knowledge of the distribution profiles of phytohormones in plant organs, tissues, and cells is still incomplete, but advances in mass spectrometry have enabled significant progress in tissue- and cell-type-specific analyses of phytohormones over the last decade. Mass spectrometry is able to simultaneously identify and quantify hormones and their related substances. Biosensors, on the other hand, offer continuous monitoring; can visualize local distributions and real-time quantification; and, in the case of genetically encoded biosensors, are noninvasive. Thus, biosensors offer additional, complementary technologies for determining temporal and spatial changes in phytohormone concentrations. In this review, we focus on recent advances in mass spectrometry–based quantification, describe monitoring systems based on biosensors, and discuss validations of the various methods before looking ahead at future developments for both approaches.
The Epigenome and Transcriptional Dynamics of Fruit Ripening
Authors: Giovannoni James , Nguyen Cuong , Ampofo Betsy , Zhong Silin , Fei Zhangjun
Published: February 2017

Fruit has evolved myriad forms that facilitate seed dispersal in varied environmental and ecological contexts. Because fleshy fruits become attractive and nutritious to seed-dispersing animals, the transition from unripe to ripe fruit represents a dramatic shift in survival strategy—from protecting unripe fruit against damaging animals to making it appealing to those same animals once ripened. For optimal fitness, ripening therefore must be tightly controlled and coordinated with seed development. Fruits, like many vegetative tissues of plants that contribute to human diets, are also subject to decay, which is enhanced as a consequence of the ripening transition. As such, ripening control has enormous relevance for both plant biology and food security. Here, we review the complex interactions of hormones and transcription factors during fleshy-fruit ripening, with an emphasis on the recent discovery that epigenome dynamics are a critical and early regulator of the cascade of molecular events that ultimately contribute to fruit maturation and ripening.
Chemical Genetic Dissection of Membrane Trafficking
Authors: Norambuena Lorena , Tejos Ricardo
Published: February 2017

The plant endomembrane system is an extensively connected functional unit for exchanging material between compartments. Secretory and endocytic pathways allow dynamic trafficking of proteins, lipids, and other molecules, regulating a myriad of biological processes. Chemical genetics—the use of compounds to perturb biological processes in a fast, tunable, and transient manner—provides elegant tools for investigating this system. Here, we review how chemical genetics has helped to elucidate different aspects of membrane trafficking. We discuss different strategies for uncovering the modes of action of such compounds and their use in unraveling membrane trafficking regulators. We also discuss how the bioactive chemicals that are currently used as probes to interrogate endomembrane trafficking were discovered and analyze the results regarding membrane trafficking and pathway crosstalk. The integration of different expertises and the rational implementation of chemical genetic strategies will improve the identification of molecular mechanisms that drive intracellular trafficking and our understanding of how trafficking interfaces with plant physiology and development.
Phase Transitions and Scaling in Systems Far from Equilibrium
Authors: Täuber Uwe C.
Published: February 2017

Scaling ideas and renormalization group approaches proved crucial for a deep understanding and classification of critical phenomena in thermal equilibrium. Over the past decades, these powerful conceptual and mathematical tools were extended to continuous phase transitions separating distinct nonequilibrium stationary states in driven classical and quantum systems. In concordance with detailed numerical simulations and laboratory experiments, several prominent dynamical universality classes have emerged that govern large-scale, long-time scaling properties both near and far from thermal equilibrium. These pertain to genuine specific critical points as well as entire parameter space regions for steady states that display generic scale invariance. The exploration of nonstationary relaxation properties and associated physical aging scaling constitutes a complementary potent means to characterize cooperative dynamics in complex out-of-equilibrium systems. This review describes dynamic scaling features through paradigmatic examples that include near-equilibrium critical dynamics, driven lattice gases and growing interfaces, correlation-dominated reaction-diffusion systems, and basic epidemic models.
A Perspective on the Role of Computational Models in Immunology
Authors: Chakraborty Arup K.
Published: February 2017

This is an exciting time for immunology because the future promises to be replete with exciting new discoveries that can be translated to improve health and treat disease in novel ways. Immunologists are attempting to answer increasingly complex questions concerning phenomena that range from the genetic, molecular, and cellular scales to that of organs, whole animals or humans, and populations of humans and pathogens. An important goal is to understand how the many different components involved interact with each other within and across these scales for immune responses to emerge, and how aberrant regulation of these processes causes disease. To aid this quest, large amounts of data can be collected using high-throughput instrumentation. The nonlinear, cooperative, and stochastic character of the interactions between components of the immune system as well as the overwhelming amounts of data can make it difficult to intuit patterns in the data or a mechanistic understanding of the phenomena being studied. Computational models are increasingly important in confronting and overcoming these challenges. I first describe an iterative paradigm of research that integrates laboratory experiments, clinical data, computational inference, and mechanistic computational models. I then illustrate this paradigm with a few examples from the recent literature that make vivid the power of bringing together diverse types of computational models with experimental and clinical studies to fruitfully interrogate the immune system.
Microglia Function in the Central Nervous System During Health and Neurodegeneration
Authors: Colonna Marco , Butovsky Oleg
Published: February 2017

Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration. Recent observations about microglia ontogeny combined with extensive gene expression profiling and novel tools to study microglia biology have allowed us to characterize the spectrum of microglial phenotypes during development, homeostasis, and disease. In this article, we review recent advances in our understanding of the biology of microglia, their contribution to homeostasis, and their involvement in neurodegeneration. Moreover, we highlight the complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases.
Computer Simulations of Intrinsically Disordered Proteins
Authors: Chong Song-Ho , Chatterjee Prathit , Ham Sihyun
Published: February 2017

The investigation of intrinsically disordered proteins (IDPs) is a new frontier in structural and molecular biology that requires a new paradigm to connect structural disorder to function. Molecular dynamics simulations and statistical thermodynamics potentially offer ideal tools for atomic-level characterizations and thermodynamic descriptions of this fascinating class of proteins that will complement experimental studies. However, IDPs display sensitivity to inaccuracies in the underlying molecular mechanics force fields. Thus, achieving an accurate structural characterization of IDPs via simulations is a challenge. It is also daunting to perform a configuration-space integration over heterogeneous structural ensembles sampled by IDPs to extract, in particular, protein configurational entropy. In this review, we summarize recent efforts devoted to the development of force fields and the critical evaluations of their performance when applied to IDPs. We also survey recent advances in computational methods for protein configurational entropy that aim to provide a thermodynamic link between structural disorder and protein activity.
From a Deficit of Democracy to a Technocratic Order: The Postcrisis Debate on Europe
Authors: Sánchez-Cuenca Ignacio
Published: February 2017

The political problems of democratic legitimacy related to the construction of the European Union have mutated deeply during the crisis. The survival of the Eurozone has exacted a high toll on democratic principles. National representative democracy has been weakened due to the imperatives of economic integration. The technocratic elements of European integration (independent agencies, binding rules on economic matters) have expanded dramatically in scope. In the past, the technocratic dimension was circumscribed to efficiency-enhancing policies; during the crisis, it has been extended to issues with clear distributional consequences (such as the burden of adjustment between debtor and creditor countries). The resulting paradox is that in a time of growing “politicization” of European affairs, the technocratic bias of the European Union has “depoliticized” economic issues. This article reviews the recent debates about the tension between technocracy and democracy in the context of European supranational integration.