bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic dissection of seed vigour under artificial ageing conditions using two joined maize recombinant inbred line populations
Authors: Ku Lixia , Cui Xinjian , Cheng Fangfang , Guo Shulei , Qi Jianshuang , Tian Zhiqiang , Han Tuo , Ren Zhenzhen , Zhang Liangkun , Su Huihui , Chen Yanhui 
Published: October 2014

AbstractSeed vigour plays an important role in agricultural production, and seeds with high sowing quality are necessary for improving agriculture production. In our study, two connected maize recombinant inbred line (RIL) populations derived from Yu82 × Shen137 and Yu537A × Shen137 crosses were evaluated for the mean germination time (MGT) and other related traits under three artificial ageing treatments. We used meta‐analysis to integrate genetic maps and identify quantitative trait loci (QTLs) across the two populations. In total, 74 QTLs and 20 meta‐QTLs (mQTLs) were identified. Four key mQTLs, mQTL2‐2, mQTL5‐4, mQTL6 and mQTL8, which contained initial QTLs with R2 values >10% and included 5–9 initial QTLs, may be hot spots of important QTLs for the associated traits. Twenty‐two key candidate genes associated with four seed vigour‐related traits mapped to 14 mQTLs. In particular, the GRMZM2G163749, GRMZM2G122172/GRMZM2G554885/GRMZM2G122871 and GRMZM2G150367 genes mapped within the important mQTL5–4, mQTL6 and mQTL8 regions, respectively. Fine mapping for the genetic regions of these three mQTLs merits further study and could be utilized for marker‐assisted breeding.
Effects of freeze–thaw on aggregate stability and the organic carbon and nitrogen enrichment ratios in aggregate fractions
Authors: Chai Y. J. , Zeng X. B. , E S. Z. , Bai L. Y. , Su S. M. , Huang T. 
Published: October 2014

AbstractSoil samples from the Hexi Corridor located in the arid regions of Northwestern China were collected from a site that had received fertilizer applications for 23 years. Effects of freeze–thaw on aggregate stability and the organic carbon (OC) and nitrogen (N) enrichment ratios in water stable aggregate (WSA) fractions were investigated. In treatments combining the application of N fertilizer with green manure (GN) or straw (SN), the percentage of >0.25 mm WSA fraction was not significantly different from the control soil that received no fertilizer or organic amendment. After a freeze–thaw cycle, the percentages of the >0.25 mm WSA fraction in the GN and SN treatments showed no change, but the size of this fraction in the other treatments decreased. In addition, the organic carbon (OC) and N enrichment ratios in the >0.25 mm WSA fraction in GN and SN treatments increased after a freeze–thaw cycle. However, in this size fraction, the OC and N enrichment ratios decreased in other treatments. Both the changes of the percentages of the >0.25 mm WSA fraction and the OC and N enrichment ratios in this fraction under freeze–thaw in the GN and SN treatments exhibited the most significant increases compared with other treatments (P < 0.05). The results indicated that the GN and SN treatments could prevent the damaging effects of freeze–thaw on aggregate stability and protect soil from erosion.
Herbivore‐induced poplar cytochrome P450 enzymes of the CYP71 family convert aldoximes to nitriles which repel a generalist caterpillar
Authors: Irmisch Sandra , Clavijo McCormick Andrea , Günther Jan , Schmidt Axel , Boeckler Gerhard Andreas , Gershenzon Jonathan , Unsicker Sybille B. , Köllner Tobias G. 
Published: October 2014

SummaryNumerous plant species emit volatile nitriles upon herbivory, but the biosynthesis as well as the relevance of these nitrogenous compounds in plant–insect interactions remains unknown. Populus trichocarpa has been shown to produce a complex blend of nitrogenous volatiles, including aldoximes and nitriles, after herbivore attack. The aldoximes were previously reported to be derived from amino acids by the action of cytochrome P450 enzymes of the CYP79 family. Here we show that nitriles are derived from aldoximes by another type of P450 enzyme in P. trichocarpa. First, feeding of deuterium‐labeled phenylacetaldoxime to poplar leaves resulted in incorporation of the label into benzyl cyanide, demonstrating that poplar volatile nitriles are derived from aldoximes. Then two P450 enzymes, CYP71B40v3 and CYP71B41v2, were characterized that produce aliphatic and aromatic nitriles from their respective aldoxime precursors. Both possess typical P450 sequence motifs but do not require added NADPH or cytochrome P450 reductase for catalysis. Since both enzymes are expressed after feeding by gypsy moth caterpillars, they are likely to be involved in herbivore‐induced volatile nitrile emission in P. trichocarpa. Olfactometer experiments showed that these volatile nitriles have a strong repellent activity against gypsy moth caterpillars, suggesting they play a role in induced direct defense against poplar herbivores.
Lipidomic and proteomic characterization of platelet extracellular vesicle subfractions from senescent platelets
Authors: Pienimaeki‐Roemer Annika , Kuhlmann Katja , Böttcher Alfred , Konovalova Tatiana , Black Anne , Orsó Evelyn , Liebisch Gerhard , Ahrens Maike , Eisenacher Martin , Meyer Helmut E. , Schmitz Gerd 
Published: October 2014

BackgroundPlatelets (PLTs) in stored PLT concentrates (PLCs) release PLT extracellular vesicles (PL‐EVs) induced by senescence and activation, resembling the PLT storage lesion. No comprehensive classification or molecular characterization of senescence‐induced PL‐EVs exists to understand PL‐EV heterogeneity.Study Design and MethodsPL‐EVs from 5‐day‐stored PLCs from healthy individuals were isolated and subfractionated by differential centrifugation, filtration, and density gradient ultracentrifugation into five PLT microvesicle (PL‐MV) subfractions (Fraction [F]1‐F5) and PLT exosomes (PL‐EXs). PL‐EV size, concentration, and composition were analyzed by nanoparticle tracking analysis, flow cytometry, and lipid and protein mass spectrometry. Protein data were verified by Western blot.ResultsPL‐EVs showed overlapping mean particle sizes of 180 to 260 nm, but differed significantly in composition. Less dense, intermediate, and dense PL‐MVs enriched specific lipidomic and proteomic markers related to the plasma membrane, intracellular membranes, PLT granules, mitochondria, and PLT activation. α‐Synuclein (81% of total) accumulated in F1 and F2, amyloid‐β (Aβ) precursor protein in F3 and F4 (84%), and apolipoprotein (Apo)E (88%) and ApoJ (92%) in F3 to F5. PL‐EXs enriched lipid species and proteins, with high abundance of lipid raft, PLT adhesion, and immune response–related markers.ConclusionDifferential lipid and protein compositions of PL‐EVs suggest their unique cellular origins and functions, partly overlapping with PLT granule secretion. Dense PL‐MVs might represent autophagic vesicles released during PLT activation and apoptosis and PL‐EXs resemble lipid rafts, with a potential role in PLT aggregation and immunity. Segregation of α‐synuclein and Aβ precursor protein, ApoE, and ApoJ into less dense and dense PL‐MVs, respectively, show their differential carrier role of neurologic disease–related cargo.
The evaluation of a new apheresis device for automated red blood cell exchange procedures in patients with sickle cell disease
Authors: Quirolo Keith , Bertolone Salvatore , Hassell Kathryn , Howard Thomas , King Karen E. , Rhodes Diane K. , Bill Jerry 
Published: October 2014

BackgroundThe Spectra Optia apheresis system (SO), a blood component separator, can be used to perform red blood cell exchange (RBCX) procedures for the transfusion management of sickle cell disease (SCD) in adults and children. This study was designed to evaluate the performance of the SO RBCX protocols (exchange and depletion/exchange) in patients with SCD.Study Design and MethodsPatients with SCD and a need for an RBCX procedure as part of a chronic program or as a single procedure were enrolled in this multicenter, single‐arm, open‐label study. The primary goal of the study was to confirm that the predicted percentage of the patient's original RBCs remaining at the end of the procedure (FCRp) reflects the actual cell fraction remaining, as measured by %HbS (FCRa). Secondary endpoints included ability of the SO to achieve the desired final hematocrit (Hct) and device‐related serious adverse events (SAEs).ResultsSeventy‐two patients 12 years of age or older were enrolled in the study; 60 were evaluable. The ratio of FCRa to FCRp after the RBCX procedure was 0.90, well within the prespecified range of 0.75 to 1.25. The SO was able to achieve the desired final Hct in the evaluable population. The safety profile was favorable, and no patients had an SAE or unexpected adverse device effect or withdrew from the procedure or treatment due to an adverse event.ConclusionThe SO performed effectively and safely for both the RBCX procedure and the RBCX depletion/exchange procedure.
Why Are Agricultural Goods Not Traded More Intensively: High Trade Costs or Low Productivity Variation?
Authors: Xu Kai 
Published: October 2014

AbstractThis paper empirically studies the sizes of agricultural trade costs and productivity variation in the agriculture sector. In a general Ricardian trade model, I identify these two factors as possible causes of the observed low trade intensity of agricultural goods. Using data on bilateral trade flows, prices of agricultural goods and sectoral production from a sample of 46 countries, I estimate the variation of agricultural productivity as well as trade costs on agricultural and manufactured goods. I find that trade costs are substantial, with agricultural trade costs roughly twice as large as manufacturing trade costs. Moreover, consistent with the existing literature, I find that distance is the dominant part in the estimated trade costs. Lastly, relative to existing estimates of the heterogeneity of manufacturing productivity, the heterogeneity of agricultural productivity is large. These findings suggest that high trade costs are the main impediments to agricultural trade.
Compartment modeling of dynamic brain PET—The impact of scatter corrections on parameter errors
Authors: Häggström Ida , Schmidtlein C. Ross , Karlsson Mikael , Larsson Anne 
Published: October 2014

Purpose:The aim of this study was to investigate the effect of scatter and its correction on kinetic parameters in dynamic brain positron emission tomography (PET) tumor imaging. The 2‐tissue compartment model was used, and two different reconstruction methods and two scatter correction (SC) schemes were investigated.Methods:The gate Monte Carlo (MC) software was used to perform 2 × 15 full PET scan simulations of a voxelized head phantom with inserted tumor regions. The two sets of kinetic parameters of all tissues were chosen to represent the 2‐tissue compartment model for the tracer 3′‐deoxy‐3′‐(18F)fluorothymidine (FLT), and were denoted FLT1 and FLT2. PET data were reconstructed with both 3D filtered back‐projection with reprojection (3DRP) and 3D ordered‐subset expectation maximization (OSEM). Images including true coincidences with attenuation correction (AC) and true+scattered coincidences with AC and with and without one of two applied SC schemes were reconstructed. Kinetic parameters were estimated by weighted nonlinear least squares fitting of image derived time–activity curves. Calculated parameters were compared to the true input to the MC simulations.Results:The relative parameter biases for scatter‐eliminated data were 15%, 16%, 4%, 30%, 9%, and 7% (FLT1) and 13%, 6%, 1%, 46%, 12%, and 8% (FLT2) for K1, k2, k3, k4, Va, and Ki, respectively. As expected, SC was essential for most parameters since omitting it increased biases by 10 percentage points on average. SC was not found necessary for the estimation of Ki and k3, however. There was no significant difference in parameter biases between the two investigated SC schemes or from parameter biases from scatter‐eliminated PET data. Furthermore, neither 3DRP nor OSEM yielded the smallest parameter biases consistently although there was a slight favor for 3DRP which produced less biased k3 and Ki estimates while OSEM resulted in a less biased Va. The uncertainty in OSEM parameters was about 26% (FLT1) and 12% (FLT2) larger than for 3DRP although identical postfilters were applied.Conclusions:SC was important for good parameter estimations. Both investigated SC schemes performed equally well on average and properly corrected for the scattered radiation, without introducing further bias. Furthermore, 3DRP was slightly favorable over OSEM in terms of kinetic parameter biases and SDs.
Atovaquone Tolerance in Plasmodium falciparum Parasites Selected for High-Level Resistance to a Dihydroorotate Dehydrogenase Inhibitor
Authors: Guler Jennifer L. , White John , Phillips Margaret A. , Rathod Pradipsinh K. 
Published: October 2014

ABSTRACT
Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such “genetic cross talk” between respiration and pyrimidine biosynthesis since many antimalarial drug development programs target these two seemingly independent pathways.
Nonclinical and Pharmacokinetic Assessments To Evaluate the Potential of Tedizolid and Linezolid To Affect Mitochondrial Function
Authors: Flanagan Shawn , McKee Edward E. , Das Debaditya , Tulkens Paul M. , Hosako Hiromi , Fiedler-Kelly Jill , Passarell Julie , Radovsky Ann , Prokocimer Philippe 
Published: October 2014

ABSTRACT

Prolonged treatment with the oxazolidinone linezolid is associated with myelosuppression, lactic acidosis, and neuropathies, toxicities likely caused by impairment of mitochondrial protein synthesis (MPS). To evaluate the potential of the novel oxazolidinone tedizolid to cause similar side effects, nonclinical and pharmacokinetic assessments were conducted. In isolated rat heart mitochondria, tedizolid inhibited MPS more potently than did linezolid (average [± standard error of the mean] 50% inhibitory concentration [IC
50
] for MPS of 0.31 ± 0.02 μM versus 6.4 ± 1.2 μM). However, a rigorous 9-month rat study comparing placebo and high-dose tedizolid (resulting in steady-state area under the plasma concentration-time curve values about 8-fold greater than those with the standard therapeutic dose in humans) showed no evidence of neuropathy. Additional studies explored why prolonged, high-dose tedizolid did not cause these mitochondriopathic side effects despite potent MPS inhibition by tedizolid. Murine macrophage (J774) cell fractionation studies found no evidence of a stable association of tedizolid with eukaryotic mitochondria. Monte Carlo simulations based on population pharmacokinetic models showed that over the course of a dosing interval using standard therapeutic doses, free plasma concentrations fell below the respective MPS IC
50
in 84% of tedizolid-treated patients (for a median duration of 7.94 h) and 38% of linezolid-treated patients (for a median duration of 0 h). Therapeutic doses of tedizolid, but not linezolid, may therefore allow for mitochondrial recovery during antibacterial therapy. The overall results suggest that tedizolid has less potential to cause myelosuppression and neuropathy than that of linezolid during prolonged treatment courses. This, however, remains a hypothesis that must be confirmed in clinical studies.
In Vitro
and
In Vivo
Activities of the Nitroimidazole TBA-354 against Mycobacterium tuberculosis
Authors: Upton A. M. , Cho S. , Yang T. J. , Kim Y. , Wang Y. , Lu Y. , Wang B. , Xu J. , Mdluli K. , Ma Z. , Franzblau S. G. 
Published: October 2014

ABSTRACT

Nitroimidazoles are a promising new class of antitubercular agents. The nitroimidazo-oxazole delamanid (OPC-67683, Deltyba) is in phase III trials for the treatment of multidrug-resistant tuberculosis, while the nitroimidazo-oxazine PA-824 is entering phase III for drug-sensitive and drug-resistant tuberculosis. TBA-354 (SN31354[(
S
)-2-nitro-6-((6-(4-trifluoromethoxy)phenyl)pyridine-3-yl)methoxy)-6,7-dihydro-5
H
-imidazo[2,1-
b
][1,3]oxazine]) is a pyridine-containing biaryl compound with exceptional efficacy against chronic murine tuberculosis and favorable bioavailability in preliminary rodent studies. It was selected as a potential next-generation antituberculosis nitroimidazole following an extensive medicinal chemistry effort. Here, we further evaluate the pharmacokinetic properties and activity of TBA-354 against
Mycobacterium tuberculosis
. TBA-354 is narrow spectrum and bactericidal
in vitro
against replicating and nonreplicating
Mycobacterium tuberculosis
, with potency similar to that of delamanid and greater than that of PA-824. The addition of serum protein or albumin does not significantly alter this activity. TBA-354 maintains activity against
Mycobacterium tuberculosis
H37Rv isogenic monoresistant strains and clinical drug-sensitive and drug-resistant isolates. Spontaneous resistant mutants appear at a frequency of 3 × 10
−7
.
In vitro
studies and
in vivo
studies in mice confirm that TBA-354 has high bioavailability and a long elimination half-life.
In vitro
studies suggest a low risk of drug-drug interactions. Low-dose aerosol infection models of acute and chronic murine tuberculosis reveal time- and dose-dependent
in vivo
bactericidal activity that is at least as potent as that of delamanid and more potent than that of PA-824. Its superior potency and pharmacokinetic profile that predicts suitability for once-daily oral dosing suggest that TBA-354 be studied further for its potential as a next-generation nitroimidazole.
Verapamil Increases the Bactericidal Activity of Bedaquiline against Mycobacterium tuberculosis in a Mouse Model
Authors: Gupta Shashank , Tyagi Sandeep , Bishai William R. 
Published: October 2014

ABSTRACT

Bedaquiline is a newly approved drug for the treatment of multidrug-resistant tuberculosis, but there are concerns about its safety in humans. We found that the coadministration of verapamil with subinhibitory doses of bedaquiline gave the same bactericidal effect in mice as did the full human bioequivalent bedaquiline dosing. Adding verapamil to bedaquiline monotherapy also protected against the development of resistant mutants
in vivo
. The adjunctive use of verapamil may permit use of lower doses of bedaquiline to be used and thereby reduce its dose-related toxicities in tuberculosis patients.
Activity Spectrum of Colicins Produced by Shigella sonnei and Genetic Mechanism of Colicin Resistance in Conspecific S. sonnei Strains and Escherichia coli
Authors: Calcuttawala Fatema , Hariharan Chellaram , Pazhani Gururaja P. , Ghosh Santanu , Ramamurthy Thandavarayan 
Published: October 2014

ABSTRACT

Colicin-mediated killing is an example of allelopathy, which has been found among several bacteria. Screening of 42 strains of
Shigella sonnei
isolated from diarrheal patients revealed that 39 (93%)
S. sonnei
strains were positive for colicin production against
Escherichia coli
DH5α. In the PCR-based detection of the colicin types, 36 (92.3%) were identified as E3, 2 (5.1%) as E3 and E8, and 1 (2.6%) as E3 and E2. Representative
S. sonnei
strains producing heterologous colicins exhibited antagonism against diarrheagenic
Escherichia coli
(DEC) groups. Although it is known that mutation in the colicin receptor renders the host resistant to colicin, there is a dearth of information on the genetic characterization of such mutants. In the fluctuation test, colicin-resistant
E. coli
mutants were found to occur spontaneously at the rates of 2.51 × 10
−8
and 5.52 × 10
−8
per generation when exposed to colicins E3 and E8 and colicins E3 and E2, respectively. Genotypic characterization of colicin-resistant
E. coli
(EC
Cr
) and
S. sonnei
(SS
Cr
) strains displayed mutations in the
btuB
gene, which encodes the receptor for vitamin B
12
uptake. This gene was interrupted by various insertion sequences, such as IS
1
, IS
2
, and IS
911
. Complementation of EC
Cr
and SS
Cr
with plasmid-borne
btuB
(p
btuB
) accomplished restoration of the colicin-susceptible phenotype. The vitamin B
12
uptake assay gave an insight into the physiological relevance of the
btuB
mutation. Our studies provide insights into the latent influence of
S. sonnei
colicins in governing the existence of some of the shigellae and all of the DEC and the genetic mechanism underlying the emergence of resistance.
Surface Glycosaminoglycans Protect Eukaryotic Cells against Membrane-Driven Peptide Bacteriocins
Authors: Martín Rebeca , Escobedo Susana , Martín Carla , Crespo Ainara , Quiros Luis M. , Suarez Juan E. 
Published: October 2014

ABSTRACT

Enzymatic elimination of surface glycosaminoglycans or inhibition of their sulfation provokes sensitizing of HT-29 and HeLa cells toward the peptide bacteriocins nisin A, plantaricin C, and pediocin PA-1/AcH. The effect can be partially reversed by heparin, which also lowers the susceptibility of
Lactococcus lactis
to nisin A. These data indicate that the negative charge of the glycosaminoglycan sulfate residues binds the positively charged bacteriocins, thus protecting eukaryotic cells from plasma membrane damage.
Accumulation-Associated Protein Enhances Staphylococcus epidermidis Biofilm Formation under Dynamic Conditions and Is Required for Infection in a Rat Catheter Model
Authors: Schaeffer Carolyn R. , Woods Keith M. , Longo G. Matt , Kiedrowski Megan R. , Paharik Alexandra E. , Büttner Henning , Christner Martin , Boissy Robert J. , Horswill Alexander R. , Rohde Holger , Fey Paul D. 
Published: October 2014

ABSTRACT

Biofilm formation is the primary virulence factor of
Staphylococcus epidermidis
.
S. epidermidis
biofilms preferentially form on abiotic surfaces and may contain multiple matrix components, including proteins such as accumulation-associated protein (Aap). Following proteolytic cleavage of the A domain, which has been shown to enhance binding to host cells, B domain homotypic interactions support cell accumulation and biofilm formation. To further define the contribution of Aap to biofilm formation and infection, we constructed an
aap
allelic replacement mutant and an
icaADBC aap
double mutant. When subjected to fluid shear, strains deficient in Aap production produced significantly less biofilm than Aap-positive strains. To examine the
in vivo
relevance of our findings, we modified our previously described rat jugular catheter model and validated the importance of immunosuppression and the presence of a foreign body to the establishment of infection. The use of our allelic replacement mutants in the model revealed a significant decrease in bacterial recovery from the catheter and the blood in the absence of Aap, regardless of the production of polysaccharide intercellular adhesin (PIA), a well-characterized, robust matrix molecule. Complementation of the
aap
mutant with full-length Aap (containing the A domain), but not the B domain alone, increased initial attachment to microtiter plates, as did in
trans
expression of the A domain in adhesion-deficient
Staphylococcus carnosus
. These results demonstrate Aap contributes to
S. epidermidis
infection, which may in part be due to A domain-mediated attachment to abiotic surfaces.