bluuebunny/crossref_metadata_2025_split huggingface dataset:
ArsP: a methylarsenite efflux permease
Authors: Chen Jian , Madegowda Mahendra , Bhattacharjee Hiranmoy , Rosen Barry P. 
Published: August 2015

SummaryTrivalent organoarsenic compounds are far more toxic than either pentavalent organoarsenicals or inorganic arsenite. Many microbes methylate inorganic arsenite (As(III)) to more toxic and carcinogenic methylarsenite (MAs(III)). Additionally, monosodium methylarsenate (MSMA or MAs(V)) has been used widely as an herbicide and is reduced by microbial communities to MAs(III). Roxarsone (3‐nitro‐4‐hydroxybenzenearsonic acid) is a pentavalent aromatic arsenical that is used as antimicrobial growth promoter for poultry and swine, and its active form is the trivalent species Rox(III). A bacterial permease, ArsP, from Campylobacter jejuni, was recently shown to confer resistance to roxarsone. In this study, C. jejuni arsP was expressed in Escherichia coli and shown to confer resistance to MAs(III) and Rox(III) but not to inorganic As(III) or pentavalent organoarsenicals. Cells of E. coli expressing arsP did not accumulate trivalent organoarsenicals. Everted membrane vesicles from those cells accumulated MAs(III) > Rox(III) with energy supplied by NADH oxidation, reflecting efflux from cells. The vesicles did not transport As(III), MAs(V) or pentavalent roxarsone. Mutation or modification of the two conserved cysteine residues resulted in loss of transport activity, suggesting that they play a role in ArsP function. Thus, ArsP is the first identified efflux system specific for trivalent organoarsenicals.
PspF‐binding domain PspA1–144 and the PspA·F complex: New insights into the coiled–coil‐dependent regulation of AAA+ proteins
Authors: Osadnik Hendrik , Schöpfel Michael , Heidrich Eyleen , Mehner Denise , Lilie Hauke , Parthier Christoph , Risselada H. Jelger , Grubmüller Helmut , Stubbs Milton T. , Brüser Thomas 
Published: August 2015

SummaryPhage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ54 enhancer‐binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans‐acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ54‐dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF‐interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled‐coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled‐coil domains.
Coevolution can explain defensive secondary metabolite diversity in plants
Authors: Speed Michael P. , Fenton Andy , Jones Meriel G. , Ruxton Graeme D. , Brockhurst Michael A. 
Published: August 2015

Summary

Many plant species produce defensive compounds that are often highly diverse within and between populations. The genetic and cellular mechanisms by which metabolite diversity is produced are increasingly understood, but the evolutionary explanations for persistent diversification in plant secondary metabolites have received less attention. Here we consider the role of plant–herbivore coevolution in the maintenance and characteristics of diversity in plant secondary metabolites.

We present a simple model in which plants can evolve to invest in a range of defensive toxins, and herbivores can evolve resistance to these toxins. We allow either single‐species evolution or reciprocal coevolution.

Our model shows that coevolution maintains toxin diversity within populations. Furthermore, there is a fundamental coevolutionary asymmetry between plants and their herbivores, because herbivores must resist all plant toxins, whereas plants need to challenge and nullify only one resistance trait. As a consequence, average plant fitness increases and insect fitness decreases as number of toxins increases. When costs apply, the model showed both arms race escalation and strong coevolutionary fluctuation in toxin concentrations across time.

We discuss the results in the context of other evolutionary explanations for secondary metabolite diversification.
A chemical genetic strategy identify the PHOSTIN, a synthetic molecule that triggers phosphate starvation responses in Arabidopsis thaliana
Authors: Bonnot Clémence , Pinson Benoît , Clément Mathilde , Bernillon Stéphane , Chiarenza Serge , Kanno Satomi , Kobayashi Natsuko , Delannoy Etienne , Nakanishi Tomoko M. , Nussaume Laurent , Desnos Thierry 
Published: August 2015

Summary

Plants display numerous strategies to cope with phosphate (Pi)‐deficiency. Despite multiple genetic studies, the molecular mechanisms of low‐Pi‐signalling remain unknown. To validate the interest of chemical genetics to investigate this pathway we discovered and analysed the effects of PHOSTIN (PSN), a drug mimicking Pi‐starvation in Arabidopsis.

We assessed the effects of PSN and structural analogues on the induction of Pi‐deficiency responses in mutants and wild‐type and followed their accumulation in plants organs by high pressure liquid chromotography (HPLC) or mass‐spectrophotometry.

We show that PSN is cleaved in the growth medium, releasing its active motif (PSN11), which accumulates in plants roots. Despite the overaccumulation of Pi in the roots of treated plants, PSN11 elicits both local and systemic Pi‐starvation effects. Nevertheless, albeit that the transcriptional activation of low‐Pi genes by PSN11 is lost in the phr1;phl1 double mutant, neither PHO1 nor PHO2 are required for PSN11 effects.

The range of local and systemic responses to Pi‐starvation elicited, and their dependence on the PHR1/PHL1 function suggests that PSN11 affects an important and early step of Pi‐starvation signalling. Its independence from PHO1 and PHO2 suggest the existence of unknown pathway(s), showing the usefulness of PSN and chemical genetics to bring new elements to this field.
Middle finger length‐based tracheal intubation depth improves the rate of appropriate tube placement in children
Authors: Zhou Qing‐he , Xiao Wang‐pin , Zhou Hong‐mei 
Published: August 2015

SummaryBackgroundIt is challenging for anesthetists to determine the optimal tracheal intubation depth in children. We hypothesize that a measure three times the length of the middle finger can be used for predicting tracheal tube depth in children.MethodsEighty‐six children (4–14 years of age) were included in this study. After the children were anesthetized, a fiberoptic bronchoscope (FOB) was inserted into the trachea, the lengths from the upper incisor teeth to carina and vocal cords were measured, and a suitably sized cuffed tracheal tube was inserted into the trachea. Age‐based and middle finger length‐based formulas were used to determine the tracheal intubation depth.ResultsAll 86 children enrolled were included in this study. Compared with the age‐based intubation, the rate of appropriate tube placement was higher for middle finger length‐based intubation (88.37% vs 66.28%, P = 0.001). The proximal intubation rate was lower in middle finger length‐based intubation (4.65% vs 32.56%, P < 0.001). There was only weak evidence for a difference in the distal intubation rate between the two methods (6.97% vs 1.16%, P = 0.054). The correlation coefficient between middle finger length and optimal tracheal tube depth was larger than that between age and optimal tracheal tube depth (0.883 vs 0.845).ConclusionsOur data indicate that the appropriate tube placement rate can be improved by using three times the middle finger length as the tracheal intubation depth in children.
When flanker meets the n‐back: What EEG and pupil dilation data reveal about the interplay between the two central‐executive working memory functions inhibition and updating
Authors: Scharinger Christian , Soutschek Alexander , Schubert Torsten , Gerjets Peter 
Published: August 2015

AbstractWe investigated the interplay between inhibition and updating, two executive working memory (WM) functions. We applied a novel task paradigm consisting of flanker stimuli presented within an n‐back task and studied the interaction between inhibitory demands and load on WM updating using behavioral measures, EEG, and pupil dilation. In contrast to studies that examine the interaction between inhibitory demands and load on WM storage components, the current task paradigm allowed testing the interaction between the executive WM components updating and inhibition. We found a reduced flanker interference effect for the highest (2‐back) updating load condition compared to lower updating load conditions on most measures. We interpret these findings as indicating that inhibitory control and WM updating are closely intertwined executive functions. Increased load on updating seemed to result in an overall more activated attentional network thus enhancing inhibitory control, such that task performance is less susceptible to distracting information.
FE, a phloem‐specific Myb‐related protein, promotes flowering through transcriptional activation of FLOWERING LOCUS T and FLOWERING LOCUS T INTERACTING PROTEIN 1
Authors: Abe Mitsutomo , Kaya Hidetaka , Watanabe‐Taneda Ayako , Shibuta Mio , Yamaguchi Ayako , Sakamoto Tomoaki , Kurata Tetsuya , Ausín Israel , Araki Takashi , Alonso‐Blanco Carlos 
Published: August 2015

SummaryIn many flowering plants, the transition to flowering is primarily affected by seasonal changes in day length (photoperiod). An inductive photoperiod promotes flowering via synthesis of a floral stimulus, called florigen. In Arabidopsis thaliana, the FLOWERING LOCUS T (FT) protein is an essential component of florigen, which is synthesized in leaf phloem companion cells and is transported through phloem tissue to the shoot apical meristem where floral morphogenesis is initiated. However, the molecular mechanism involved in the long‐distance transport of FT protein remains elusive. In this study, we characterized the classic Arabidopsis mutant fe, which is involved in the photoperiodic induction of flowering, and showed that FE encodes a phloem‐specific Myb‐related protein that was previously reported as ALTERED PHLOEM DEVELOPMENT. Phenotypic analyses of the fe mutant showed that FT expression is reduced in leaf phloem companion cells. In addition, the transport of FT protein from leaves to the shoot apex is impaired in the fe mutant. Expression analyses further demonstrated that FE is also required for transcriptional activation of FLOWERING LOCUS T INTERACTING PROTEIN 1 (FTIP1), an essential regulator for selective trafficking of the FT protein from companion cells to sieve elements. These findings indicate that FE plays a dual role in the photoperiodic induction of flowering: as a transcriptional activator of FT on the one hand, and its transport machinery component, FTIP1, on the other hand. Thus, FE is likely to play a role in regulating FT by coordinating FT synthesis and FT transport in phloem companion cells.
Loss of function mutations in the rice chromomethylase OsCMT3a cause a burst of transposition
Authors: Cheng Chaoyang , Tarutani Yoshiaki , Miyao Akio , Ito Tasuku , Yamazaki Muneo , Sakai Hiroaki , Fukai Eigo , Hirochika Hirohiko 
Published: August 2015

SummaryMethylation patterns of plants are unique as, in addition to the methylation at CG dinucleotides that occurs in mammals, methylation also occurs at non‐CG sites. Genes are methylated at CG sites, but transposable elements (TEs) are methylated at both CG and non‐CG sites. The role of non‐CG methylation in transcriptional silencing of TEs is being extensively studied at this time, but only very rare transpositions have been reported when non‐CG methylation machineries have been compromised. To understand the role of non‐CG methylation in TE suppression and in plant development, we characterized rice mutants with changes in the chromomethylase gene, OsCMT3a. oscmt3a mutants exhibited a dramatic decrease in CHG methylation, changes in the expression of some genes and TEs, and pleiotropic developmental abnormalities. Genome resequencing identified eight TE families mobilized in oscmt3a during normal propagation. These TEs included tissue culture‐activated copia retrotransposons Tos17 and Tos19 (Lullaby), a pericentromeric clustered high‐copy‐number non‐autonomous gypsy retrotransposon Dasheng, two copia retrotransposons Osr4 and Osr13, a hAT‐tip100 transposon DaiZ, a MITE transposon mPing, and a LINE element LINE1‐6_OS. We confirmed the transposition of these TEs by polymerase chain reaction (PCR) and/or Southern blot analysis, and showed that transposition was dependent on the oscmt3a mutation. These results demonstrated that OsCMT3a‐mediated non‐CG DNA methylation plays a critical role in development and in the suppression of a wide spectrum of TEs. These in planta mobile TEs are important for studying the interaction between TEs and the host genome, and for rice functional genomics.
Iron deficiency anemia at admission for labor and delivery is associated with an increased risk for Cesarean section and adverse maternal and neonatal outcomes
Authors: Drukker Lior , Hants Yael , Farkash Rivka , Ruchlemer Rosa , Samueloff Arnon , Grisaru‐Granovsky Sorina 
Published: August 2015

BACKGROUNDMaternal iron deficiency anemia (IDA) impacts placenta and fetus. We evaluated effects of IDA at admission for delivery on cesarean rates, and adverse maternal and neonatal outcomes.STUDY DESIGN AND METHODSMedical records from Jerusalem (2005‐2012) identified women with a live‐birth singleton fetus in cephalic presentation of any gestational age and excluded planned cesarean, chronic/gestational diseases identified with anemia. Study population was divided into anemic and non‐anemic women using WHO criteria. Main outcome measures: cesarean rate, and adverse outcomes (maternal: packed cells transfusion, early post‐partum hemorrhage, preterm delivery; and neonatal: 5′ Apgar < 7, Neonatal Intensive Care Unit [NICU] admission, extreme birthweights). Continuous variable analysis and multivariate backward step–wise logistic regression models were prepared with Odds Ratios (OR) and 95% confidence intervals (CI).RESULTSIn all, 96,066 deliveries were registered, of which 75,660 (78.8%) were included. IDA was present in 7,977 women (10.5%). Anemia at birth was significantly associated with cesarean section (OR 1.30; 95%CI, 1.13‐1.49, p < 0.001), packed cells transfusion (OR 5.48; 95%CI, 4.57‐6.58, p < 0.001), preterm delivery (OR 1.54; 95%CI, 1.36‐1.76, p < 0.001), macrosomia (OR 1.23; 95%CI, 1.12‐1.35, p < 0.001), Large for Gestational Age (OR 1.29; 95%CI, 1.20‐1.39, p < 0.001), Apgar 5′ < 7 (OR 2.21; 95%CI, 1.84‐2.64, p < 0.001), and NICU admission (OR 1.28; 95%CI, 1.04‐1.57, p = 0.018).CONCLUSIONIron deficiency anemia at delivery is associated with an increased risk for cesarean section and adverse maternal and neonatal outcomes in otherwise healthy women. Monitoring/correction of hemoglobin concentrations even in late pregnancy may prevent these adverse events.
Oritavancin Pharmacokinetics and Bone Penetration in Rabbits
Authors: Lehoux Dario , Ostiguy Valerie , Cadieux Cordelia , Malouin Mireille , Belanger Odette , Far Adel Rafai , Parr Thomas R. 
Published: August 2015

ABSTRACT
The pharmacokinetics and bone concentrations of oritavancin were investigated after a single intravenous dose was administered to rabbits. The pharmacokinetic profile of oritavancin in rabbits showed that it is rapidly distributed to bone tissues, with concentrations remaining stable for up to 168 h, the last measured time point. Based on these findings, further evaluation of oritavancin for the treatment of infections in bone tissues is warranted.
Population Pharmacokinetics of Fosfomycin in Critically Ill Patients
Authors: Parker Suzanne L. , Frantzeskaki Frantzeska , Wallis Steven C. , Diakaki Chryssa , Giamarellou Helen , Koulenti Despoina , Karaiskos Ilias , Lipman Jeffrey , Dimopoulos George , Roberts Jason A. 
Published: August 2015

ABSTRACT

This study describes the population pharmacokinetics of fosfomycin in critically ill patients. In this observational study, serial blood samples were taken over several dosing intervals of intravenous fosfomycin treatment. Blood samples were analyzed using a validated liquid chromatography-tandem mass spectrometry technique. A population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Five hundred fifteen blood samples were collected over one to six dosing intervals from 12 patients. The mean (standard deviation) age was 62 (17) years, 67% of patients were male, and creatinine clearance (CL
CR
) ranged from 30 to 300 ml/min. A two-compartment model with between-subject variability on clearance and volume of distribution of the central compartment (

V
c

) described the data adequately. Calculated CL
CR
was supported as a covariate on fosfomycin clearance. The mean parameter estimates for clearance on the first day were 2.06 liters/h,

V
c

of 27.2 liters, intercompartmental clearance of 19.8 liters/h, and volume of the peripheral compartment of 22.3 liters. We found significant pharmacokinetic variability for fosfomycin in this heterogeneous patient sample, which may be explained somewhat by the observed variations in renal function.
Antischistosomal Activity of Oxindolimine-Metal Complexes
Authors: de Moraes Josué , Dario Bruno S. , Couto Ricardo A. A. , Pinto Pedro L. S. , da Costa Ferreira Ana M. 
Published: August 2015

ABSTRACT

In recent years, a class of oxindole-copper and -zinc complex derivatives have been reported as compounds with efficient proapoptotic activity toward different tumor cells (e.g., neuroblastomas, melanomas, monocytes). Here we assessed the efficacy of synthesized oxindole-copper(II), -zinc(II), and -vanadyl (VO
2+
) complexes against adult
Schistosoma mansoni
worms. The copper(II) complexes (50% inhibitory concentrations of 30 to 45 μM) demonstrated greater antischistosomal properties than the analogous zinc and vanadyl complexes regarding lethality, reduction of motor activity, and oviposition.
Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria
Authors: Yu Yanbao , Zielinski Martin D. , Rolfe Melanie A. , Kuntz Melissa M. , Nelson Heidi , Nelson Karen E. , Pieper Rembert 
Published: August 2015

ABSTRACT

Differential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (≥38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB
4
and LTC
4
, mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified.
Reversal of the Drug Binding Pocket Defects of the AcrB Multidrug Efflux Pump Protein of Escherichia coli
Authors: Soparkar Ketaki , Kinana Alfred D. , Weeks Jon W. , Morrison Keith D. , Nikaido Hiroshi , Misra Rajeev 
Published: August 2015

ABSTRACT

The AcrB protein of
Escherichia coli
, together with TolC and AcrA, forms a contiguous envelope conduit for the capture and extrusion of diverse antibiotics and cellular metabolites. In this study, we sought to expand our knowledge of AcrB by conducting genetic and functional analyses. We began with an AcrB mutant bearing an F610A substitution in the drug binding pocket and obtained second-site substitutions that overcame the antibiotic hypersusceptibility phenotype conferred by the F610A mutation. Five of the seven unique single amino acid substitutions—Y49S, V127A, V127G, D153E, and G288C—mapped in the periplasmic porter domain of AcrB, with the D153E and G288C mutations mapping near and at the distal drug binding pocket, respectively. The other two substitutions—F453C and L486W—were mapped to transmembrane (TM) helices 5 and 6, respectively. The nitrocefin efflux kinetics data suggested that all periplasmic suppressors significantly restored nitrocefin binding affinity impaired by the F610A mutation. Surprisingly, despite increasing MICs of tested antibiotics and the efflux of
N
-phenyl-1-naphthylamine, the TM suppressors did not improve the nitrocefin efflux kinetics. These data suggest that the periplasmic substitutions act by influencing drug binding affinities for the distal binding pocket, whereas the TM substitutions may indirectly affect the conformational dynamics of the drug binding domain.

IMPORTANCE
The AcrB protein and its homologues confer multidrug resistance in many important human bacterial pathogens. A greater understanding of how these efflux pump proteins function will lead to the development of effective inhibitors against them. The research presented in this paper investigates drug binding pocket mutants of AcrB through the isolation and characterization of intragenic suppressor mutations that overcome the drug susceptibility phenotype of mutations affecting the drug binding pocket. The data reveal a remarkable structure-function plasticity of the AcrB protein pertaining to its drug efflux activity.